Research on (Rifapentine)-C-reactive protein-edema


TARGET-SYDROM RELATIONSHIP DRUG-TARGET-SYDROM RELATIONSHIP

Year Title Journal Abstract
2021MRI contributes to accurate and early diagnosis of non-radiographic HLA-B27 negative axial spondyloarthritis.J Transl MedNonradiographic axial spondyloarthropathies (nr-axSpA) are diagnosed by the absence of radiographic sacroiliitis and the presence of bone marrow edema (BME) on magnetic resonance imaging (MRI). According to the classification criteria of the international Assessment of Spondyloarthritis Society (ASAS), structural changes to sacroiliac joints (SIJs) on MRI cannot be used as criteria in the absence of BME. However, less than half the Asian patients with clinically active axSpA show BME. The incidence of human leukocyte antigen (HLA)-B27 is low in Asian populations, which makes it more difficult to identify nr-axSpA. We used MRI to evaluate the structural damage to SIJs in patients with nr-axSpA with and without BME with the aim of identifying the best methodology for accurate diagnosis, especially in populations with less common BME and HLA-B27.One hundred three patients with inflammatory back pain were included in this prospective study. No patient's radiograph met the definition of positive modified New York criteria. BME and structural damage to SIJ including sclerosis and erosion were assessed independently on coronal and axial short-tau inversion recovery and T1-weighted spin echo MRI scans by two well-trained musculoskeletal radiologists using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Demographics of patients were collected. Disease characteristics and structural damage were analyzed in patients with and without BME on SIJ MRI. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of structural damage.All individuals in the cohort had at least one abnormal finding on SIJ MRI, including BME or structural damage; 36 of 103 patients had BME. We identified a significant positive correlation between SPARCC scores and severe erosion assessed by focal joint space widening (fJSW) (p = 0.001) in these 36 patients. Fifty-eight of the 103 enrolled patients fulfilled the ASAS criteria for nr-axSpA in the either absence or presence of BME. Of these 58 patients, 57 and 19 had erosions or fJSW, respectively, and the presence of BME was significantly correlated with fJSW (phi score of 0.319 and p = 0.015). We demonstrated a significant positive correlation between fJSW and either the presence or the severity of BME in patients with nr-axSpA who met the ASAS definition. There was a positive correlation between BME and fJSW across the whole study cohort (phi score of 0.389; p < 0.001). The area under the ROC curve (AUC) for fJSW on SIJ MRI was 0.736, p < 0.001. In both HLA-B27-positive and -negative groups, BME was more common in the presence of fJSW (phi scores of 0.370 and 0.377, p = 0.018 and 0.003, respectively) and SPARCC scores were higher in patients with fJSW (p < 0.001 and p = 0.005). We also identified a positive correlation between fJSW and BME in patients with nr-axSpA and normal serum levels of C-reactive protein (phi score of 0.362 and p = 0.001).Structural damage detected on SIJ MRI, sclerosis, erosions and fJSW may be present in patients without detectable inflammation on SIJ MRI. However, fJSW is significantly correlated with the severity of inflammation seen on SIJ MRI, which contributes to the accurate diagnosis of nr-axSpA, and it could be used as an alternative diagnostic test for nr-axSpA in the general population, especially for those who do not carry the HLA-B27 gene, Asian patients without BME, or patients with normal serum inflammatory biomarkers.
2021Ulinastatin as an Adjuvant Therapy to Restricting Volumes of Resuscitation Fluid Strategy for Patients with Septic Shock after Initial Management.Evid Based Complement Alternat MedSeptic shock is the most serious complication of sepsis, leading to unacceptably high morbidity and mortality worldwide. Fluid resuscitation using crystalloids has become the mainstay of early and aggressive treatment of severe sepsis and septic shock, while increased daily fluid balances from day 2 until day 7 have been related with increased mortality. Recently, pharmacological management has been recommended to combine with appropriate fluid resuscitation for the treatment of septic shock. In this study, we compared the clinical efficacy of restricting volumes of resuscitation fluid strategy with or without intravenous infusion of ulinastatin (UTI) in treating patients with septic shock and additionally examined the patient's changes of the extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), systemic vascular resistance index (SVRI), cardiac function, lactic acid (LA) level, coagulation function, and renal function. The study included 182 patients with septic shock, among which 89 patients had undergone restricting volumes of resuscitation fluid strategy with intravenous infusion of UTI and 93 patients had undergone restricting volumes of resuscitation fluid strategy alone. It was found that patients with septic shock after restricting volumes of resuscitation fluid strategy with intravenous infusion of UTI showed an increased SVRI concomitant with declined PVPI and EVLWI, increased mean artery pressure (MAP), cardiac output (CO), left ventricular ejection fraction (LVEF), stroke volume (SV), and heart rate (HR), declined levels of cardiac troponin I (cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP), reduced LA level along with shortened prothrombin time (PT) and partially activated thrombin time (PATT), and decreased levels of blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) when comparable to those after restricting volumes of resuscitation fluid strategy alone ( < 0.05). We also observed fewer scores of the Acute Physiology and Chronic Health Evaluation (APACHE II) and the sequential organ failure assessment (SOFA) in patients undergoing restricting volumes of resuscitation fluid strategy with intravenous infusion of UTI than those undergoing restricting volumes of resuscitation fluid strategy alone ( < 0.05). According to the above data, it is concluded that UTI as an adjuvant therapy for restricting volumes of resuscitation fluid strategy in treating septic shock may decrease the LA level, attenuate the inflammatory response, reduce vascular permeability, prevent pulmonary edema, and restore cardiac and renal functions.
2021Antioxidant and Anti-Inflammatory Effects of and : In Silico, Biochemical and Histological Study.FoodsIn this study, the antioxidant and anti-inflammatory effects of and aqueous extracts were examined in a carrageenan-induced acute inflammation model. Some markers of inflammation such as hematological parameters, fibrinogen and C-reactive protein were measured. Variables reflecting oxidative stress included thiobarbituric acid reactive substances (TBARS), advanced oxidation of protein products (AOPP), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione were determined in both inflamed foci and erythrocytes. The in silico molecular docking simulation showed that the main components of and bound to toll-like receptor 6 (TLR6) with high affinities. Moreover, histological examinations of paw edema were carried out. Both and ameliorated the induced inflammation and oxidative stress status as outlined by anti-edematous, antioxidant and anti-inflammatory activities. Our investigation lends pharmacological support to the medical uses of these spices in the management of inflammatory disorders and oxidative damage. The results of the in silico assay satisfactory explain the in vivo effects as compared with indomethacin.
2021Quantification of bone marrow edema in rheumatoid arthritis by using high-speed T2-corrected multiecho acquisition of H magnetic resonance spectroscopy: a feasibility study.Clin RheumatolTo determine whether high-speed T2-corrected multiecho (HISTO) sequences can quantify bone marrow edema (BME) in the capitate bone in rheumatoid arthritis (RA), and whether the HISTO fat fraction (FF) reflects therapeutic effectiveness.In this prospective study, 25 RA patients (19 women; average age, 45.08 ± 13.48 years) underwent 3.0-T MRI with HISTO at the baseline and after 4, 8, and 12 weeks of treatment. Rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet (PLT) count, and 28-joint Disease Activity Score using ESR (DAS28-ESR) were recorded on the day of each MRI examination by a rheumatologist blinded to the MRI findings. In addition, 21 healthy subjects (15 women; age, 49.17 ± 6.56 years) underwent only the HISTO sequence at a single time point.HISTO FF values were significantly higher in the control group (74.5% ± 3.1%; range, 68.6-79.3%) than in the patient group (55.8% ± 17.7%; range, 15.6-79.0%) at the baseline (independent-samples t-test: t = 5.257, P = 0.000). The changes in HISTO FF and DAS28-ESR showed moderate negative correlations with each other at 4, 8, and 12 weeks, and all of them were statistically significant (P < 0.05). As the HISTO FF increased, the DAS28-ESR decreased.The HISTO sequence can measure the bone marrow FF of the wrist joint bones in RA patients. The HISTO FF value increased as the DAS28-ESR decreased. The HISTO sequence may help quantify BME in RA and help monitor the effectiveness of RA treatment. Key Points •The HISTO sequence could measure the bone marrow FF of the wrist joint bones. •FF value increased as the DAS28-ESR decreased in RA patients. •The HISTO sequence can monitor the therapeutic effect of RA.
2021TNF-α Receptor Inhibitor Alleviates Metabolic and Inflammatory Changes in a Rat Model of Ischemic Stroke.Antioxidants (Basel)Hyperglycemia and inflammation, with their augmented interplay, are involved in cases of stroke with poor outcomes. Interrupting this vicious cycle thus has the potential to prevent stroke disease progression. Tumor necrosis factor-α (TNF-α) is an emerging molecule, which has inflammatory and metabolic roles. Studies have shown that TNF-α receptor inhibitor R-7050 possesses neuroprotective, antihyperglycemic, and anti-inflammatory effects. Using a rat model of permanent cerebral ischemia, pretreatment with R-7050 offered protection against poststroke neurological deficits, brain infarction, edema, oxidative stress, and caspase 3 activation. In the injured cortical tissues, R-7050 reversed the activation of TNF receptor-I (TNFRI), NF-κB, and interleukin-6 (IL-6), as well as the reduction of zonula occludens-1 (ZO-1). In the in vitro study on bEnd.3 endothelial cells, R-7050 reduced the decline of ZO-1 levels after TNF-α-exposure. R-7050 also reduced the metabolic alterations occurring after ischemic stroke, such as hyperglycemia and increased plasma corticosterone, free fatty acids, C reactive protein, and fibroblast growth factor-15 concentrations. In the gastrocnemius muscles of rats with stroke, R-7050 improved activated TNFRI/NF-κB, oxidative stress, and IL-6 pathways, as well as impaired insulin signaling. Overall, our findings highlight a feasible way to combat stroke disease based on an anti-TNF therapy that involves anti-inflammatory and metabolic mechanisms.
2021Validation of Remote Dielectric Sensing (ReDS) in Monitoring Adult Patients Affected by COVID-19 Pneumonia.Diagnostics (Basel)Remote dielectric sensing (ReDS) is a non-invasive electromagnetic wave technology which provides an accurate reading of lung fluid content, and it has been reported as a valid tool in monitoring heart failure patients. Considering that morphological alterations in COVID-19 include pulmonary edema, the purpose of the present study was to evaluate the reliability of ReDS technology in assessing the excess of lung fluid status in COVID-19 pneumonia, as compared to CT scans. In this pilot single center study, confirmed COVID-19 patients were enrolled on admission to an intermediate care unit. Measurements with the ReDS system and CT scans were performed on admission and at weeks 1 and 2. Eleven patients were recruited. The average change in ReDS was -3.1 ± 1.7 after one week ( = 0.001) and -4.6 ± 2.9 after two weeks ( = 0.006). A similar trend was seen in total CT score (-3.3 ± 2.1, = 0.001). The level of agreement between ReDS and CT changes yielded a perfect result. Statistically significant changes were observed in lactate dehydrogenase, lymphocytes, and c-reactive protein over 2 weeks. This pilot study shows that ReDS can track changes in lung involvement according to the severity of COVID-19. Further studies to detect early clinical deterioration are needed.
2021Central retinal vein occlusion in a patient using the antipsychotic drug olanzapine: a case report.J Med Case RepWe report our findings in a patient who developed central retinal vein occlusion (CRVO) and was a chronic user of olanzapine, an antipsychotic medication.A 50-year-old Caucasian man, non-smoker, was referred to our clinic with the chief complaint of floater appearance in his left eye for the past 3 days. His past medical history indicated that he had been taking antipsychotic drugs (olanzapine) for about 3 years, with no other systemic disease or risk factors for CRVO. In the examination, his best-corrected visual acuity (BCVA) was 0.7 in the left eye. The fundus showed signs of nonischemic CRVO with subhyaloid hemorrhage and intraretinal hemorrhage in the posterior pole and superior and inferior retina, without macular edema, confirmed by optical coherence tomography (OCT). We ruled out other probable differential diagnoses and risk factors which lead to CRVO through a complete physical exam and blood analysis (complete blood count, glucose, urea, creatinine, lipid profile, erythrocyte sedimentation rate, C-reactive protein, prothrombin time, partial thromboplastin time, Bleeding time (BT), fibrinogen level, proteins, antiphospholipid antibodies, homocysteine blood level, antithrombin III, protein C and S, factor V Leiden, prothrombin mutation, angiotensin-converting enzyme level, other autoantibodies, and human leukocyte antigen [HLA]-B51). Finally, we confirmed the probable side effect of olanzapine in CRVO, which has not been previously reported. A possible pro-thrombogenic mechanism of olanzapine at the molecular level is an affinity for 5-HTserotonin receptors. Blocking these receptors results in increased platelet aggregation and increased blood coagulability.These results indicate that CRVO can be a complication of chronic use of antipsychotic medications such as olanzapine, as shown for the first time in our case report. Clinicians should question patients who develop a sudden CRVO whether they are using antipsychotic medications such as olanzapine.
2021Immunomodulatory and Mechanistic Considerations of (HS) in Dysfunctional Immune Responses: A Systematic Review.Front Immunolcalyx (HS) water decoction extract is a commonly consumed beverage with various pharmacological properties. This systematic review examines the possible effect of HS intake on immune mediators. The Scopus and PUBMED databases were searched for all human and animal studies that investigated the effect of HS administration on immune related biomarkers. For each of the immune biomarkers, the mean, standard deviation and number of subjects were extracted for both the HS treated and untreated group. These values were used in the computation of standardized mean difference (SMD). Statistical analysis and forest plot were done with R statistical software (version 3.6.1). Twenty seven (27) studies met the eligibility criteria. Twenty two (22) of the studies were used for the meta-analysis which included a total of 1211 subjects. The meta-analysis showed that HS administration significantly lowered the levels of TNF-α (n=10; pooled SMD: -1.55; 95% CI: -2.43, -0.67; P < 0.01), IL-6 (n=11; pooled SMD:-1.09; 95% CI: -1.77, -0.40; P < 0.01), IL-1β (n=7; pooled SMD:-0.62; 95% CI: -1.25, 0.00; P = 0.05), Edema formation (n=4; pooled SMD: -2.29; 95% CI: -4.47, -0.11; P = 0.04), Monocyte Chemoattractant Protein -1 (n=4; pooled SMD: -1.17; 95% CI: -1.78, -0.57; P < 0.01) and Angiotensin converting enzyme cascade (n=6; pooled SMD: -0.91; 95% CI: -1.57, -0.25; P < 0.01). The levels of IL-10 (n=4; pooled SMD: -0.38; 95% CI: -1.67, 0.91; P = 0.56), Interleukin 8 (n=2; pooled SMD:-0.12; 95% CI: -0.76, 0.51; P = 0.71), iNOS (n=2; pooled SMD:-0.69; 95% CI: -1.60, 0.23 P = 0.14) and C- Reactive Protein (n=4; pooled SMD: 0.05; 95% CI: -0.26, 0.36; P = 0.75), were not significantly changed by HS administration. Some of the results had high statistical heterogeneity. HS may be promising in the management of disorders involving hyperactive immune system or chronic inflammation.
2021Case Report: A Case of Trimethoprim/Sulfamethoxazole-Triggered Hypotensive Shock: Cytokine Release Syndrome Related to Immune Checkpoint Inhibitors and Drug-Induced Hypersensitivity Syndrome.Front OncolCurrently, only a few reports exist on the cytokine release syndrome (CRS) as one of the severe immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs). Notably, it is very rare that grade 4 CRS related to ICI therapy overlaps with the drug-induced hypersensitivity syndrome (DiHS). A 46-year old woman with metastatic kidney cancer had grade 3 interstitial pneumonitis induced by four cycles of combination therapy of anti-programmed death-1 and anti-cytotoxic T lymphocyte-4 antibodies after right cytoreductive nephrectomy. Prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) was started concomitantly with prednisolone therapy to treat the interstitial pneumonitis. She developed hypotensive shock when reducing the dosage of prednisolone, and required intubation and ventilation using vasopressors at the intensive care unit. She subsequently exhibited prominent leukocytosis and an increased level of C-reactive protein, suggesting markedly increased cytokine levels. Interestingly, facial edema and erythema increased in association with pyrexia, leukocytosis, liver dysfunction, and renal failure, suggesting that she developed DiHS. She received hemodialysis three times, a plasma exchange, and anti-interleukin-6 therapy to treat severe renal dysfunction, a thrombotic thrombocytopenic purpura-suspected condition, and possible grade 4 CRS, respectively. Although these therapies did not elicit sufficient effects, high-dose administration of intravenous immunoglobulin was successful. With steroid mini-pulse therapy and the subsequent administration of prednisolone, she recovered successfully. To the best of our knowledge, this is the first report that ICIs and TMP/SMX can induce hypotensive shock accompanied with CRS and DiHS during immunosuppressive therapy for an irAE. Importantly, the prophylactic administration of TMP/SMX should be performed cautiously to avoid severe drug reactions such as CRS or DiHS.
2021Acute Pancreatitis in Children: The Clinical Profile at a Tertiary Hospital.CureusObjectives The clinical course and progression of acute pancreatitis are poorly understood to date, necessitating more studies of clinical profiles during the disease. Moreover, understanding the etiologies and clinical presentations of acute pancreatitis (AP) in children can contribute to early diagnosis and, hence, earlier interventions. Therefore, this article aims to study the clinical profiles of children with acute pancreatitis (AP) in relation to complications and other variables. Study design We retrospectively studied 56 patients who presented with AP to the pediatric department in Salmaniya Medical Complex between January 2006 and December 2017. Cases of chronic pancreatitis and ages above 12 years were excluded. The data concerned demographics, etiology, clinical data, hospital course, and outcomes. Results The study included 56 patients aged a mean of 8.46 years (male:female - 33:23). The average hospital stay was 7.68 days. Patients received parenteral feeds a mean of 2.77 days. All patients had an ultrasound, nine required CT scans (16.1%), and five MRIs (8.9%). There were 18 local complications (32.1%): pseudocysts (n=3, 5.36%), cholangitis (n=2, 3.6%), and edema (n=13, 23.2%). There were 23 intensive care unit (ICU) admissions (41.1%). No mortalities occurred but there were six recurrences (10.7%). Symptoms of abdominal pain, vomiting, fever, and nausea occurred in 100%, 57.1%, 35.7%, and 23.2% of patients, respectively. Etiologies were 41.1% biliary, 23.2% idiopathic, 19.6% traumatic, and 8.93% drug-induced. Leukocytes were elevated in 20 patients (35.7%), c-reactive protein (CRP) in five (8.93%), serum amylase in 45 (80.4%), and urinary amylase in all 56 patients (100%). Conclusion Most pediatric AP cases were attributed to biliary causes followed by trauma. Age was significantly correlated with complication rates (P=0.013). Abdominal pain was a more common symptom than vomiting. Leukocytosis was associated with ICU admissions. There was no significant relation between c-reactive protein, serum amylase, or urinary amylase, and complications or ICU admissions. Pediatric AP was self-limiting and there were no fatalities.
2021Treadmill Exercise during Pregnancy Decreased Vulnerability to Neonatal Hypoxia-Ischemia through Reducing Inflammation and Increasing Antiapoptotic Gene Expressions and Antioxidant Capacity in Rats.Stroke Res TreatThe purpose of present study was to assess the impact of maternal treadmill exercise during pregnancy on inflammation, oxidative stress, expression of Bax and Bcl-2 genes, and brain-derived neurotrophic factor (BDNF) level in neonatal rat brain after the hypoxia-ischemia injury. . A total of 24 female Wistar rats were utilized in this research. Two groups are randomly considered for rats: (1) not exercised through pregnancy and (2) exercised during pregnancy. Offsprings were divided into four groups including after delivery: (1) sham, (2) sham/exercise (sham/EX), (3) HI, and (4) HI+exercise. HI was induced in pups at postnatal day 8. Neurobehavioral tests were done seven days after HI induction. Then, the brain tissue was taken from the skull to estimate Bcl-2 and Bax gene expressions, BDNF, cerebral edema, infarct volume, inflammatory factors, oxidative stress, and neurological function.The BDNF level in the HI+exercise group was considerably higher than the HI, sham, and sham/EX groups. Tumor necrosis factor (TNF-), C-reactive protein (CRP), and the whole oxidant capacity (TOC) levels in the HI group were significantly higher than the sham and sham/EX groups. TNF-, CRP, and TOC levels in the HI+exercise group were significantly lower than the HI group. Total antioxidant capacity (TAC) level in the HI+exercise group was significantly higher than the HI group. Infarct volume and edema percent in the HI+exercise group were significantly lower than the HI group. Neurological function in the HI+exercise group was significantly better than the HI group. Bax expression in the HI+exercise group was significantly lower than the HI group. Bcl-2 expression in the HI+exercise group was significantly higher than the HI group. In the sham group, BDNF, TNF-, CRP, TAC, TOC, edema levels, and neurological function had no significant difference with the sham/EX group.It appears that the maternal treadmill exercise during pregnancy exerts a supportive impact against neonatal HI brain injury through increasing antioxidant capacity, Bcl-2 expression, and BDNF levels and decreasing inflammation that is resulted in the lower infarct volume and sensorimotor dysfunction.
2021A mechanistic study on the inhibition of bacterial growth and inflammation by Nerium oleander extract with comprehensive in vivo safety profile.BMC Complement Med TherNerium oleander (L.) is well known traditionally used medicinal plant with several pharmacological activities. However, the anti-bacterial, anti-inflammatory activity and in vivo toxicity potential of floral parts of this plant are not reported. Therefore the present study was designed to investigate these activities of Nerium oleander ethanolic flower extract (NOEE) in different animal models.Antimicrobial activity of plant extract was compared with five different antibiotics using the disk diffusion method. The time-killing kinetic assay and bacterial killing mechanism of NOEE were also performed. Anti-inflammatory activity was assessed using granuloma induced by cotton-pellet, rat paw edema induced by carrageenan and levels of different inflammatory biomarkers on healthy Wistar rats. The protein and mRNA expressions of nitric oxide (NO), prostaglandin E (PGE), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also measured. Acute (14 days) and sub-acute (28 days) oral toxicity studies were also performed on healthy Sprague Dawley rats.NOEE produced highly significant (P < 0.005) and significant (P < 0.05) zones of inhibition at 30 mg/mL and 20 mg/mL respectively against most of the tested bacterial strains. NOEE produced a more drop in viable counts of Gram-negative isolates within 20 min. After 12 h exposure with NOEE, the SEM images of MRSA showed the destruction of cell membrane. NOEE showed highly significant (P < 0.005) anti-inflammatory activity in cotton-pellet and carrageenan inflammatory models. In addition, treatment with NOEE also decreased the production of NO, PGE, TNF-α and IL-1β in the rat paw after treated with carrageenan. Similarly, NOEE also suppressed the inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, and cyclooxygenase-2 (COX-2) mRNA expressions. It is also showed highly significant reduction in total leukocyte count (73.09%) and C-reactive protein levels (54.60%). NOEE also inhibited COX-1, COX-2, 5-LO and 12-LO in a highly significant manner. Moreover, acute and sub-acute toxicity studies of NOEE in rats confirm the toxicity with hepatotoxicity at higher doses (2000 mg/kg) i.e. four times greater than the therapeutic dose.It is concluded that crude flower extract of N. oleander is a potent antimicrobial and anti-inflammatory agent with no toxicity potential at therapeutic doses.
2021Impact of Perihematomal Edema on Infectious Complications after Spontaneous Intracerebral Hemorrhage.J Stroke Cerebrovasc DisIntracerebral hematoma involves two mechanisms leading to brain injury: the mechanical disruption of adjacent brain tissue by the hematoma and delayed neurological injury. Delayed neurological injury involves perihematomal edema (PHE) formation. Infectious complications following intracerebral hemorrhage (ICH) are a significant contributor to post-ICH recovery. We sought to identify a correlation between PHE volumes and infectious complications following ICH. We also sought to explore the clinical impact of this association.This retrospective study included 143 patients with spontaneous ICH. CT scans were performed on admission, and 3 h, 24 h, and 72 h following admission. Hematoma and PHE volumes were calculated using a semi-automatic method. The absolute PHE volume at each time point and changes in PHE volume (ΔPHE) were calculated. Neutrophil to lymphocyte ratio (NLR) and serum C-reactive protein (CRP) levels were measured from the obtained blood samples. Neurological deterioration (ND) was assessed in all patients.Infectious complications were associated with ΔPHE (P < 0.01), whereas there was no association between infectious complications and ΔPHE (P = 0.09) or ΔPHE (P = 0.81). There was a positive correlation between ΔPHE and NLR (r = 0.85, 95% CI: 0.79-0.90, P < 0.01) and between ΔPHE and CRP levels (r = 0.89, 95% CI: 0.84-0.92, P < 0.01). The ND rate in the group of patients with infectious complications comorbid with high ΔPHE was higher than the other patient groups (P < 0.01).This study revealed a correlation between ΔPHE and infectious complications after spontaneous ICH, which was associated with markers of systemic inflammation. This phenotype linkage is a negative cascade that drives ND.
2021Activation of the Nrf2/HO-1 signaling pathway by dimethyl fumarate ameliorates complete Freund's adjuvant-induced arthritis in rats.Eur J PharmacolThe nuclear factor erythroid 2-related factor (Nrf2) signaling pathway has recently emerged as a novel therapeutic target in treating various diseases. Therefore, the present study aimed to assess the protective role of the Nrf2 activator, dimethyl fumarate (DMF) in the complete Freund's adjuvant (CFA)- induced arthritis model. DMF (25, 50, and 100 mg/kg) and dexamethasone (2 mg/kg) were orally administered for 14 days. Pain-related tests, paw volume, and arthritic scores were measured weekly. Serum TNF-α, IL-1β, cyclic citrullinated peptide (CCP), C-reactive protein (CRP), and rheumatoid factor (RF) levels were estimated. Nitrite, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), catalase (CAT), and myeloperoxidase (MPO) levels were also evaluated. NF-κB, Nrf2, HO-1, and COX-2 levels were estimated in the joint tissue. DMF treatment exerted anti-arthritic activity by enhancing the nociceptive threshold, improving arthritis scores, and reducing paw edema. Also, DMF suppressed changes in oxidative stress markers and inflammatory mediators and enhanced Nrf2 and HO-1 levels in CFA-injected rats. These findings indicate that the anti-arthritic activity of DMF may be mediated by the activation of the Nrf2/HO-1 pathway, which reduced oxidative damage and inflammation.
2021Levofloxacin-Induced Acute Pancreatitis.CureusDrug-induced pancreatitis is a rare entity accounting for less than 2% of acute pancreatitis (AP). Quinolones are commonly used antimicrobials with occasional reports of pancreatitis. We present the case of a 74-year-old man who was diagnosed with acute cystitis five days before hospital admission and was treated with levofloxacin (LVF). Two days after initiating LVF he experienced fever, severe abdominal pain, and nausea. The initial assessment revealed leukocytosis, elevated C-reactive protein, and a significant elevation of amylase and lipase. On abdominal ultrasound, the head of the pancreas revealed an hypoechogenic region suggestive of inflammatory edema. A diagnosis of AP was established. The drug was withdrawn along with supportive care, with complete resolution of the symptoms. No other probable causes of AP were found after further investigation. Although rare, LVF-induced pancreatitis should be considered when managing a patient with AP. Increasing physician awareness is vital to the prompt recognition of this entity.
2021Venous thromboembolism in hospital emergency room. A retrospective study on climatic effect.Environ ResSeveral cardiovascular conditions exhibit seasonality in frequency and mortality, but little is known about the seasonality of Venous ThromboEmbolism (VTE), a very relevant medical condition, and seasonal influences are still conflicting. Patients having co-morbidities, individual suffered from dyspnea, swelling, edema of lower limb, pain (chest, lower limbs) are admitted frequently to the hospital emergency room (HER), particularly. Both mark a potential risk for VTE, that can be increased also by seasonality. A four years retrospective analysis (2016-2019) was carried out in individuals and patients admitted to the HER of the Hospital of Catania (a Mediterranean city of Sicily, Italy) to evaluate the VTE frequency and its seasonal differences, common symptoms, potential usage of some common laboratory tests. Dyspnea, swelling, edema of lower limb and pain (chest, lower limbs) were considered to suspect pulmonary embolism (PE) or for deep vein thrombosis of lower limb (DVT). Platelet count, platelet volume, fibrinogen, C-reactive protein, and D-dimer were considered. VTE frequency per year was 2.9/10,000 (2016), 4.9/10,000 (2017) 3.6/10,000 (2018), and 5.1/10,000 (2019) respectively. Dyspnea was highly frequent for PE, edema and lower limb pain were frequent in DVT patients. Fibrinogen, C reactive protein, and D-dimer values were found raised in all the VTE patients. Platelet volume was found higher in DVT than PE VTE events that occurred in warm periods were modestly greater (57 VTE: 38 DVT, 19 PE) compared to cold months (52 VTE: 34 DVT, 18 PE). Our results could be explained by the increased sweating due to the high temperatures, which in turn, can affect both on plasma concentration and on hematocrit value coupled to the reduction in atmospheric pressure determining both a hyper-coagulative condition. Climate seasonal characteristics, and environmental conditions in Catania city (Sicily) may be as reasonable items in expecting on different VTE rates in warm period compared to cold. This study highlights no specific symptoms, and confirms the common lab tests for individuals and patients admitted to HER as simple and helpful tools in initiating none or mini-invasive diagnostic strategy for the VTE. Finally, the climate/seasonality coupled with latitude can have a direct influence on the incidence of DVT.
2021Role of systemic corticosteroids in orbital cellulitis: a meta-analysis and literature review.Braz J OtorhinolaryngolThe standard management of orbital cellulitis is to administer a combination of intravenous broad-spectrum antibiotics along with treatment of associated sinusitis.The purpose of this study was to evaluate whether the addition of corticosteroids could lead to earlier resolution of inflammation and improve disease outcome.We independently searched five databases (PubMed, SCOPUS, Embase, the Web of Science, and the Cochrane database) for studies published as recent as December 2019. Of the included studies, we reviewed orbital cellulitis and disease morbidity through lengths of hospitalization, incidence of surgical drainage, periorbital edema, vision, levels or C-reactive protein, and serum WBC levels in order to focus on comparing steroid with antibiotics treated group and only antibiotics treated group.Lengths of hospitalization after admission as diagnosed as orbital cellulitis (SMD=-4.02 [-7.93; -0.12], p-value=0.04, I=96.9%) decrease in steroid with antibiotics treated group compared to antibiotics only treated group. Incidence of surgical drainage (OR=0.78 [0.27; 2.23], p-value=0.64, I=0.0%) was lower in the steroid with antibiotics treated group compared to the antibiotics only treated group.Use of systemic steroids as an adjunct to systemic antibiotic therapy for orbital cellulitis may decrease orbital inflammation with a low risk of exacerbating infection. Based on our analysis, we concluded that early use of steroids for a short period can help shorten hospitalization days and prevent inflammation progression.
2021Obstructive Sleep Apnea is Related with the Risk of Retinal Vein Occlusion.Nat Sci SleepRetinal vein occlusion (RVO) was a vision-threatening retinal vascular disorder, however, the relationship between obstructive sleep apnea (OSA) and RVO risk remained unclear.A total of 45 RVO cases and 45 controls between April 2018 and April 2020 were included. All the participants underwent full-night polysomnography (PSG) and thus detected the severity of OSA. Besides, the relationship between the apnea-hypopnea index (AHI) and oxidative and inflammatory biomarkers, including 8-hydroxy-2 deoxyguanosine (8-OHdG), C-reactive protein (CRP), interleukin 1 beta (IL1β), interleukin 6 (IL6) and tumor necrosis factor alpha (TNFα) were detected. The incidences of macular edema (ME) and neovascular glaucoma (NVG) were detected in a three-months follow-up.In this case-control study, it was found that OSA incidence was increased in the RVO cases comparing with the cataract controls. Advanced analyses about the RVO subtypes demonstrated that incidence of OSA was higher in the central RVO (CRVO) cases comparing with branch RVO (BRVO) cases. Plasma samples from OSA cases demonstrated relatively higher concentrations of oxidative stress parameters and inflammatory biomarkers, including 8-OHdG, CRP, IL1β, and IL6, in the RVO cases. Significant linear correlations between AHI and oxidative/inflammatory biomarkers were detected, and advanced analyses on the OSA subtypes demonstrated that these biomarkers were significantly higher in cases with later stages of OSA. In a three months follow-up, an impaired visual activity improvement rate and increased ME incidence in the OSA group among all the RVO cases were detected.OSA was related with an increased incidence of RVO. Besides, OSA would lead to increased oxidative and inflammatory biomarkers concentrations in the RVO cases. OSA could be used as a harmful prognostic factor of visual activity improvement and ME incidences. These findings highlighted the role of OSA in the development of RVO.
C-Reactive Protein Triggers Cell Death in Ischemic Cells.Front ImmunolC-reactive protein (CRP) is the best-known acute phase protein. In humans, almost every type of inflammation is accompanied by an increase of CRP concentration. Until recently, the only known physiological function of CRP was the marking of cells to initiate their phagocytosis. This triggers the classical complement pathway up to C4, which helps to eliminate pathogens and dead cells. However, vital cells with reduced energy supply are also marked, which is useful in the case of a classical external wound because an important substrate for pathogens is disposed of, but is counterproductive at internal wounds (e.g., heart attack or stroke). This mechanism negatively affects clinical outcomes since it is established that CRP levels correlate with the prognosis of these indications. Here, we summarize what we can learn from a clinical study in which CRP was adsorbed from the bloodstream by CRP-apheresis. Recently, it was shown that CRP can have a direct effect on blood pressure in rabbits. This is interesting in regard to patients with high inflammation, as they often become tachycardic and need catecholamines. These two physiological effects of CRP apparently also occur in COVID-19. Parts of the lung become ischemic due to intra-alveolar edema and hemorrhage and in parallel CRP increases dramatically, hence it is assumed that CRP is also involved in this ischemic condition. It is meanwhile considered that most of the damage in COVID-19 is caused by the immune system. The high amounts of CRP could have an additional influence on blood pressure in severe COVID-19.
2021Higher levels of circulating ANGPTL2 are associated with macular edema in patients with type 2 diabetes.Medicine (Baltimore)Macular edema (ME) is an inflammatory disease characterized by increased microvascular permeability. Here, we proposed that plasma angiopoietin-like protein 2 (ANGPTL2) level may be related to the severity of ME patients with type 2 diabetes mellitus (T2DM). In this cross-sectional study, 172 T2DM patients were recruited and divided into clinically significant macular edema (CSME), non-CSME (nCSME), and control groups. Serum ANGPTL2 level was quantified by ELISA and best corrected vision acuity (BCVA) was detected. After adjust age, sex, body mass index (BMI), and duration of diabetes variables, ANGPTL2 performed statistics difference among CSME-, nCSME-groups, and control group (4.46 [3.97, 4.96, 95%CI] ng/mL in CSME group, 3.80 [3.42, 4.18, 95%CI] ng/mL in nCSME-group, 3.33 [3.03, 3.63, 95%CI] ng/mL in control, P < .01). After adjustment of confounding factors, high levels of circulating ANGPTL2 were related with the diagnosis of ME, BCVA, and C reactive protein (CRP) through univariate regression analysis (P < .05). Meanwhile, in the multiple regression model, ANGPTL2 took the mainly effect proportion for the diagnosis of diabetic macular edema (DME), with a LogWorth value 3.559 (P < .001). Our study suggested that elevated circulating ANGPTL2 may be associated with the development of DME and the severity of visual impairment in patients with type 2 diabetes.
2021Multisystem inflammatory syndrome in children during the COVID-19 pandemic in Turkey: first report from the Eastern Mediterranean.Clin RheumatolWe aimed to describe the typical clinical and laboratory features and treatment of children diagnosed with multisystem inflammatory syndrome in children (MIS-C) and to understand the differences as compared to severe/critical pediatric cases with COVID-19 in an eastern Mediterranean country.Children (aged <18 years) who diagnosed with MIS-C and severe/critical pediatric cases with COVID-19 and were admitted to hospital between March 26 and November 3, 2020 were enrolled in the study.A total of 52 patients, 22 patients diagnosed with COVID-19 with severe/critical disease course and 30 patients diagnosed with MIS-C, were included in the study. Although severe COVID-19 cases and cases with MIS-C share many clinical and laboratory features, MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe cases (p<0.001 for each). Of all, 53.3% of MIS-C cases had the evidence of myocardial involvement as compared to severe cases (27.2%). Additionally, C-reactive protein (CRP) and white blood cell (WBC) are the independent predictors for the diagnosis of MIS-C, particularly in the existence of conjunctival injection and rash. Corticosteroids, intravenous immunoglobulin (IVIG), and biologic immunomodulatory treatments were mainly used in MIS-C cases rather than cases with severe disease course. There were only three deaths among 52 patients, one of whom had Burkitt lymphoma and the two cases with severe COVID-19 of late referral.Differences between clinical presentations, acute phase responses, organ involvements, and management strategies indicate that MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19. Conjunctival injection and higher CRP and low WBC count are reliable diagnostic parameters for MIS-C cases. Key Points • MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe/critical pediatric cases with COVID-19. • Higher CRP and low total WBC count are the independent predictors for the diagnosis of MIS-C. • MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19.
2021Cervical Necrotizing Fasciitis, Diagnosis and Treatment of a Rare Life-Threatening Infection.Ear Nose Throat JNecrotizing fasciitis is a relatively uncommon and potentially life-threatening soft tissue infection, with morbidity and mortality approaching 25% to 35%, even with optimal treatment. The challenge of diagnosis for necrotizing soft tissue infections (NSTIs) is their rarity, with the incidence of approximately 1000 cases annually in the United States. Given the rapid progression of disease and its similar presentation to more benign processes, early and definitive diagnosis is imperative.Signs and symptoms of NSTIs in the early stages are virtually indistinguishable from those seen with abscesses and cellulitis, making definitive diagnosis difficult. The clinical presentation will depend on the pathogen and its virulence factors which ultimately determine the area and depth of invasion into tissue. There are multiple laboratory value scoring systems that have been developed to support the diagnosis of an NSTI. The scoring system with the highest positive (92%) and negative (96%) predictive value is the laboratory risk indicator for necrotizing fasciitis (LRINEC). The score is determined by 6 serologic markers: C-reactive protein (CRP), total white blood cell (WBC) count, hemoglobin, sodium, creatinine, and glucose. A score ≥ 6 is a relatively specific indicator of necrotizing fasciitis (specificity 83.8%), but a score <6 is not sensitive (59.2%) enough to rule out necrotizing fasciitis. In terms of imaging, computed tomography (CT) imaging, while more sensitive (80%) than plain radiography in detecting abnormalities, is just as nonspecific. Computed tomography imaging of NSTIs demonstrates fascial thickening (with potential fat stranding), edema, subcutaneous gas, and abscess formation. Magnetic resonance imaging (MRI) has demonstrated sensitivity of 100% and specificity of 86%, though MRI may not show early cases of fascial involvement of necrotizing fasciitis.Necrotizing soft tissue infections are rapidly progressive and potentially fatal infections that require a high index of clinical suspicion to promptly diagnose and aggressive surgical debridement of affected tissue in order to ensure optimal outcomes.Prompt surgical and infectious disease consultation is necessary for the treatment and management of these patients. While imaging is useful for further characterization, it should not delay surgical consultation. Necrotizing soft tissue infection remains a clinical diagnosis, although plain radiography, CT imaging, and ultrasound can provide useful clues. In general, the management of these patients should include rapid diagnosis, using a combination of clinical suspicion, laboratory data (LRINEC score), and imaging (MRI being the recommended imaging modality), prompt infectious disease and surgical consultation, surgical debridement, and delayed reconstruction. Laboratory findings that can more strongly suggest a diagnosis of NSTI include elevated CRP, elevated WBC, low hemoglobin, decreased sodium, and increased creatinine. Imaging findings include fascial thickening (with potential fat stranding), edema, subcutaneous gas, and abscess formation. Broad-spectrum antibiotics should be started in all cases of suspected NSTI. Surgical debridement, however, remains the lynchpin for treatment of cervical necrotizing fasciitis.
2021Appraisal of Anti-Arthritic and Anti-Inflammatory Potential of Folkloric Medicinal Plant Peganum Harmala.Endocr Metab Immune Disord Drug TargetsPeganum harmala is traditionally used to manage rheumatoid arthritis (RA) and other inflammatory conditions. However, its use against RA has not been scientifically evaluated. The current study was designed to assess the anti-arthritic and anti-inflammatory activities of the methanolic extract of P. harmala leaves by in vitro and in vivo methods.The in vitro assays were carried out to determine the effect of plant extract on inhibition of egg albumin denaturation and human red blood cell membrane (HRBC) stabilization. Moreover, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity was performed to determine the antioxidant potential. In vivo anti-arthritic activity was performed by determining the curative effect against Complete Freund's adjuvant (0.1 ml). The plant extract was administered to rats orally at 200, 400 and 600 mg/kg/day for 21 days.The values of IC50 of plant extract in protein denaturation, stabilization of HRBC and DPPH assays were 77.54 mg/ml, 23.90 mg/ml and 58.09 µg/ml respectively. Moreover, the plant extract significantly attenuated the poly-arthritis and weight loss, anemia and paw edema. The plant extract restored the level of C-reactive protein, rheumatoid factor, alanine transaminase, aspartate transaminase and alkaline phosphatase in poly-arthritic rats. Moreover, the plant extract restored the immune organs weight in treated rats. Treatment with P. harmala also significantly subdued the oxidative stress by reinstating superoxide dismutase, reduced glutathione, catalase and malondialdehyde in poly-arthritic rats. The plant extract notably restored the prostaglandin-E2 and tumor necrosis factor (TNF)-α in the serum of poly-arthritic rats.It was concluded that P. harmala extract had potential antioxidant, anti-inflammatory and antiarthritic activities which primarily might be attributed to alkaloids, flavonoids and phenols.
2021Association of myocardial hemorrhage and persistent microvascular obstruction with circulating inflammatory biomarkers in STEMI patients.PLoS OneMyocardial hemorrhage (IMH) and persistent microvascular obstruction (MVO) are associated with impaired myocardial recovery and adverse clinical outcomes in STEMI patients. However, their relationship with circulating inflammatory biomarkers is unclear in human patients.Twenty consecutive patients referred for primary percutaneous coronary intervention of first STEMI were included in a prospective study. Blood sampling was performed at admission, 4, 12, 24, 48 hours, 7 and 30 days after reperfusion for inflammatory biomarker (C reactive protein, fibrinogen, interleukin-6 (IL-6) and neutrophils count) assessment. At seven days, cardiovascular magnetic resonance (CMR) was performed for infarct size, MVO and IMH assessment. Median infarct size was 24.6% Interquartile range (IQR) [12.0-43.5] of LV mass and edema was 13.2% IQR [7.7-36.1] of LV mass. IL-6 reached a peak at H24 (5.6 pg/mL interquartile range (IQR) [2.5-17.5]), CRP at H48 (11.7 mg/L IQR [7.1-69.2]), fibrinogen one week after admission (4.4 g/L IQR [3.8-6.7]) and neutrophils at H12 (9.0 G/L IQR [6.5-12.7]). MVO was present in 11 patients (55% of the study population) and hemorrhage in 7 patients (35%). Patients with IMH had significantly higher IL-6, CRP, fibrinogen, and neutrophils levels compared to patients without IMH. Patients with persistent MVO had significantly higher CRP, fibrinogen and neutrophils level compared to patients without MVO, but identical IL-6 kinetics.In human patients with acute myocardial infarction, intramyocardial hemorrhage appears to have a stronger relationship with inflammatory biomarker release compared to persistent MVO. Attenuating myocardial hemorrhage may be a novel target in future adjunctive STEMI treatments.
2020Clinical Characteristics of 47 Death Cases With COVID-19: A Retrospective Study at a Tertiary Center in Lahore.CureusIntroduction Coronavirus disease 2019 (COVID-19) presents with a wide spectrum of symptoms, ranging from patients being asymptomatic to having life-threatening acute respiratory distress syndrome (ARDS). COVID-19 emerged as a pandemic and has led to multiple causalities worldwide. A better understanding of the clinical characteristics of the COVID-19 patients and their disease course will aid in better management of these patients and hence may positively impact their outcomes as well. Methodology This was a retrospective observational study conducted fromApril 15, 2020, toAugust 31, 2020, after gaining institutional review board approval at the University of Lahore Teaching Hospital, Lahore, Pakistan. A total of 47 patients with severe disease who had died due to COVID-19 during this period were enrolled by the consecutive method. Patients were evaluated for their epidemiological, biochemical, clinical, and radiological features. The modified Radiographic Assessment of Lung Edema (mRALE) score was used to calculate the extent of alveolar opacities and percentages of lung involvement in chest radiographs. Furthermore, patients' management plans were also evaluated. Data were analyzed using SPSS Statistics version 23 (IBM, Armonk, NY). Results The mean age of the patients was 61.53 ±13.35 years. The male-to-female ratio was 2:1, and the mean BMI was 28.05 ±3.52 kg/m. Diabetes was the most prevalent comorbidity among the patients (32, 68.1%), followed by hypertension (six, 12.8%), ischemic heart disease (five, 10.6%), and chronic kidney disease (four, 8.5%) respectively. The predominant symptom observed among patients was cough (95%), followed by shortness of breath (93%), fever (63%), sputum (23%), and gastrointestinal symptoms (6.4%). The mean D-dimer was 1,567.13 ±1,903.77 ng/mL, mean ferritin was 1,730.34 ±1,382.35 ng/mL, mean C-reactive protein (CRP) was 202.59 ±104.97 mg/dl, and the mean neutrophil-to-lymphocyte ratio was 10.50 ±9.58. Bilateral lung involvement was seen among 40 (85.11%) patients whereas unilateral right lung involvement was reported in three (6.38%) and unilateral left lung involvement in four (8.51%) respectively. The mean mRALE score for bilateral lung involvement was 18.78 ±4.89. The mean area radiologically involved in bilateral lung fields was 72.12 ±18.45%, followed by unilateral right lung involvement of 67.87 ±15.97%, and unilateral left lung involvement of 61.38 ±17.95% in the cohort respectively. The most common type of radiological pathology was diffuse ground-glass opacities, which was observed in 18 (38%) patients. Most patients received antibiotics (39, 63.83%), while nine (19%) received tocilizumab, four (8.5%) had antiviral therapy, and three (6.4%) were given plasma treatment. All patients received glucocorticoids and anticoagulation. The most common cause of death was ARDS, which was observed in 12 (25.5%) patients. Conclusion This study significantly demonstrated that most cases were males above 50 years of age with chronic medical comorbidities of diabetes, hypertension, and ischemic heart disease. COVID-19 has a predilection for multisystem involvement leading to mortality. In addition, elevated D-dimer and neutrophil-to-lymphocyte ratio may be indicative of a poor prognosis. A combination of antimicrobials had no positive impact on the outcomes in this cohort. It is difficult to predict the efficacy of tocilizumab and remdesivir as only a few patients in the cohort received these drugs.
2020Clinical presentation and diagnosis of acute postoperative spinal implant infection (PSII).J Spine SurgAcute postoperative infections after surgical interventions on the spinal column are associated with prolonged treatment duration, poor patient outcomes, and a high socioeconomic burden. In the field of joint replacement, guidelines have been established with recommendations for the diagnosis and treatment of such complications, but in spinal surgery there are no definitions permitting distinction between early and late infections and no specific instructions for their management. Various factors increase the risk of acute postoperative infection, including blood transfusions, leakage of cerebrospinal fluid, urinary tract infection, injury of the dura mater, an American Society of Anesthesiologists (ASA) score >2, obesity, diabetes mellitus, and surgical revision. We suggest defining all infections occurring within the first 4 weeks after spinal surgery as early infections. The symptoms are pain at rest, on motion, and/or pressure pain, abnormal warmth, local erythema, circumscribed swelling of the wound, and newly occurring secretion. Together with laboratory parameters such as C-reactive protein (CRP) and leukocytes, a central role is played by imaging in the form of magnetic resonance imaging (MRI), although diagnosis can be hampered by the presence of postoperative fluid collections such as edema or hematoma or by artifacts from an implant. Once an infection has been confirmed, immediate wound revision with debridement and rinsing (sodium hypochlorite) is essential. Intraoperatively it may prove advantageous to use jet lavage and administer vancomycin. We recommend leaving the implant in place in cases of acute postoperative infection. Patients who are not conditional for surgery can first receive antibiotic suppression treatment before surgery at a later date. In such cases initial computed tomography (CT)-guided aspiration or drain insertion can take place.
2021Plasma heat shock protein 90 levels in patients with spondyloarthritis and their relation to structural changes: a cross-sectional study.Biomark MedHeat shock protein 90 (Hsp90) is a molecular chaperone regulating immune response. We aimed to assess systemic Hsp90 as a biomarker for spondyloarthritis (SpA). Total of 80 axial SpA (axSpA) and 22 psoriatic arthritis patients and a corresponding number of age- and sex-matched healthy controls (HC) were included. Plasma Hsp90 levels were measured by ELISA. Hsp90 was significantly increased in axSpA patients compared with HC (median interquartile range: 15.7 [10.5-19.8] vs 8.3 [6.6-11.8] ng/ml, p < 0.001). Moreover, Hsp90 was superior to C-reactive protein in differentiating axSpA (and both radiographic axSpA [r-axSpA] and nonradiographic-axSpA) from HC. Hsp90 levels correlated with bone marrow edema of sacroiliac joints in r-axSpA patients (r = 0.594, p = 0.019). Hsp90 could become a biomarker for active inflammation in r-axSpA, and can better distinguish axSpA patients from healthy subjects than C-reactive protein.
2020miR-7-5p Affects Brain Edema After Intracerebral Hemorrhage and Its Possible Mechanism.Front Cell Dev BiolTo explore the relationship between miR-7-5p and brain edema after intracerebral hemorrhage and the role of butylphthalide (NBP) in brain edema after intracerebral hemorrhage. Routine blood testing, C-reactive protein results, and computed tomography data were collected 1, 7, and 14 days after intracerebral hemorrhage in six patients. Levels of MMP-9, ZO-1, occludin, IL-6, TNF-α, and miR-7-5p were detected in each patient's serum. Sixty male Sprague-Dawley rats were randomly divided into sham operation, intracerebral hemorrhage, and NBP treatment groups. Dry-wet weight was used to assess brain edema, and Evans blue staining was used to assess the permeability of the blood-brain barrier. Expression levels of IL-6, TNF-α, ZO-1 and occludin, PI3K, AKT, p-AKT, AQP4, and miR-7-5p were analyzed in the rat brains. The blood neutrophil-lymphocyte ratio (NLR) on day 1 was associated with the area of brain edema on day 7. The expression of miR-7-5p decreased after intracerebral hemorrhage, and as a result, the inhibition of the PI3K/AKT pathway was weakened. The decreased inhibition of the PI3K/AKT pathway resulted in an increase in AQP4 expression, which further aggravated brain edema. NBP can upregulate the expression of miR-7-5p, affecting these pathways to reduce brain edema. After intracerebral hemorrhage, miR-7-5p expression in brain tissue is reduced, which may increase the expression of AQP4 by activating the PI3K/AKT pathway. NBP can inhibit this process and reduce brain edema.
2021PSB 603 - a known selective adenosine A2B receptor antagonist - has anti-inflammatory activity in mice.Biomed PharmacotherA adenosine receptors are present in a wide spectrum of tissues, especially on cells of the immune system. Since these particular receptors have the lowest, of all adenosine receptor subtypes, affinity for adenosine they are believed to play a special role in immunological processes associated with elevated adenosine levels such as inflammation. The aim of this preliminary study was to determine the potential anti-inflammatory properties of compound PSB-603, a potent and selective adenosine A receptor antagonist, in two different experimental models of local and systemic inflammation. In a model of inflammation induced by local carrageenan administration paw edema was measured using a pletysmometer. Additionally, levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and reactive oxygen species (ROS) were determined in the inflamed paw. Using the mouse model of peripheral inflammation induced by intraperitoneal (ip) administration of zymosan A, the influence of the A antagonist on the infiltration of neutrophils into the peritoneum and its effect on the plasma levels of CRP, TNF-α, and IL-6 were investigated. The results showed that PSB-603 administered at a dose of 5 mg/kg b.w. ip significantly reduced inflammation in both tested models. Particularly, it significantly decreased levels of the inflammatory cytokines IL-6, TNF-α and of ROS in the inflamed paw and reduced inflammation of the peritoneum by significantly decreasing the infiltration of leukocytes. Additionally, in the latter model, no statistically significant difference was observed in the CRP level between the control group without inflammation and the group which has been treated with the PSB-603 compound. Thus, the results may indicate the anti-inflammatory activity of adenosine A receptor antagonists in two different models of inflammation.
2021Prognostic significance of serum translocator protein in patients with spontaneous intracerebral hematoma:preliminary findings.Neurol Res: The aim of this study was to measure the level of translocator protein (TSPO) in patients with intracerebral hematoma (ICH) and to determine whether TSPO can predict ICH outcomes.: Patients with ICH were recruited at Wujin Hospital Affiliated with Jiangsu University between January 2018 and May 2020. The level of TSPO and inflammatory factors were analyzed by enzyme-linked immunosorbent assay (ELISA). A receiver operating characteristic curve (ROC) analysis was applied to assess the accuracy of TSPO for predicting patient outcomes.: The median of TSPO was 2.26 ng/ml. The lower- (46 cases) and higher-(51 cases) TSPO groups were thus divided based on the median value. The perihematomal edema (PHE) volume in the lower TSPO group was 6.3 ± 1.3 ml which was significantly lower than that in higher-TSPO group (14.8 ± 3.5 ml) (p < 0.05). The serum level of the interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) in the higher-TSPO group was significantly higher than that in the lower TSPO group (p < 0.05). The Spearman's correlation found that TSPO concentrations significantly correlated with PHE volume, modified Rankin Scale score (MRS), IL-1β, IL-6, TNF-α, and CRP concentrations. The area under the ROC (AUC), specificity, sensitivity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and Diagnostic Odds Ratio (DOR) of TSPO was 0.932, 82.1%, 89.9%, 5.02, 0.12, and 40.8, respectively, which was more reliable than other inflammatory factors.: The TSPO may a reliable biomarker in predicting the prognosis of ICH patients.
2020[Clinical characteristics and management of Petersen hernia after gastrectomy in patients with gastric cancer].Zhonghua Wei Chang Wai Ke Za ZhiPetersen hernia is a rare but severe complication after gastrectomy, which has been reported by very few studies. This study is dedicated to summarize the clinical characteristics and management of Petersen hernia after gastrectomy in patients with gastric cancer in order to provide reference to clinical practice. A descriptive case-control study was carried out. All the qualified patients were screened from the database of digestive malignancies in Nanjing Drum Tower Hospital. The inclusion criteria were as follows: Petersen hernia confirmed during operation; previous gastrectomy history due to gastric cancer; complete clinical data. The clinical manifestation, perioperative data and follow-up outcome were summarized. A total of 12 qualified patients were included. They were all male with a mean age of (65.3±8.5) years old, and whose clinical presentation had last for (6~143) hours (median: 21 hours). Common complaints included abdominal pain and bloating. All the patients were admitted to the emergency department. Preoperative CT showed dilatation and effusion of small intestine. Other imaging manifestations included whirlpool sign, target sign, mesenteric retraction or congestion and edema, abdominal and pelvic effusion, etc. Hematological examination showed white blood cell count, ratio of neutrophils, procalcitonin and C-reactive protein were higher than the normal range. The median interval to previous gastrectomy is 20.5 (0.5-55.0) months. The previous gastrectomy of 12 cases included 2 cases of laparoscopic surgery and 10 of laparotomies. Ten cases underwent emergency surgery immediately, and 2 cases underwent surgery after ineffective conservative treatment. Six cases received small bowel restoration without bowel resection, and the other 6 cases received small bowel resection with a mean length of 76 (11~300) cm. Six cases were transferred into ICU with a stay of (2.5±0.8) days. One case deceased at postoperative day 2, due to subtotal small bowel resection, and the other 11 cases survived without grade III or above complication according to Clavien-Dindo classification. The overall postoperative hospitalization was (9.2±3.6) days. During the postoperative follow-up, no acute gastrointestinal symptoms or acute abdomen recurred. Petersen hernia is more common in male, whose onset and progress are rapid and emergent, and prognosis is poor.
2020[Clinical features of hydronephrosis induced by retroperitoneal fibrosis: 17 cases reports].Beijing Da Xue Xue Bao Yi Xue BanTo investigate the clinical features and outcome of hydronephrosis induced by retroperitoneal fibrosis (RPF), and to evaluate the effect of corticosteroid based therapy combined with surgical intervention of ureteral obstruction.A total of 17 RPF patients with hydronephrosis hospitalized in Peking University International Hospital from May 2016 to December 2019 were analyzed retrospectively.The median age was 56 (53, 65) years, the male to female ratio was 2.4 : 1, and the disease duration was 4.00 (0.83, 8.00) months. The initial symptoms included back pain (9 cases), abdominal pain (6 cases), oliguria (2 cases) and lower limb edema (3 cases). Eight patients presented left hydronephrosis, 1 right hydronephrosis and 8 bilateral hydronephrosis. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were both elevated in 13 patients (76.5%, =17). Immunoglobin (Ig) G4 increased in 5 cases (29.4%, =17). IgG, IgE and IgA increased in 4 cases (30.8%, =13), 4 cases (30.8%, =13) and 1 case (7.7%, =13), respectively. Among 12 patients who underwent biopsy, 3 patients were diagnosed with IgG4-relate disease. The level of IgG4 in the tissues varied, 6 cases expressed less than 10 per high power field (HPF) or no expression (50.0%). Only 2 cases expressed 10-30/HPF (16.7%), and 4 cases revealed more than 30/HPF (33.3%). Among the 17 patients with ureteral obstruction, no urinary drainage procedure was needed in 4 patients who had mild ureteral obstruction, whereas, ureteral stenting was carried out in the other 13 cases before drug treatment. Time was too short to evaluate the effect of urinary drainage procedures in 4 patients. For the rest, ureterolysis had to be performed in 3 cases after failed ureteral stent insertion. Successful drain removal was accomplished in all of these 9 patients and the mean time to drain removal was (6.7±3.0) months. In addition, 10 patients had complete medical records after an average follow-up time of 5 (3-13) months. Levels of ESR, CRP, IgG4, IgG, IgE, IgA were 54.0 (36.3, 98.5) mm/h, 26.8 (8.7, 53.0) mg/L, 1.34 (0.55, 3.36) g/L, 16.3 (13.0, 21.1) g/L, 40.5 (31.4, 203.0) IU/mL, 2.51 (1.82, 3.25) g/L at baseline, which all decreased predominantly after treatment. ESR, CRP, IgG4, IgG, IgE and IgA dropped by 38.5 (23.5, 54.3) mm/h ( < 0.01), 23.0 (5.5, 52.0) mg/L ( < 0.05), 0.92 (0.40, 2.85) g/L ( < 0.01), 6.5 (1.7, 9.1) g/L ( < 0.05), 23.7 (4.8, 162.0) IU/mL ( < 0.05) and 0.77 (0.32, 1.26) g/L ( < 0.05), respectively. Size of mass measured by CT/MRI imaging became smaller significantly and hydronephrosis relieved.Onset of RPF is insidious and lack of specific initial symptoms. Corticosteroid based therapy combined with surgical intervention of relieving obstruction is effective.
2021Mucocutaneous disease and related clinical characteristics in hospitalized children and adolescents with COVID-19 and multisystem inflammatory syndrome in children.J Am Acad DermatolLittle is known about mucocutaneous disease in acutely ill children and adolescents with COVID-19 and multisystem inflammatory syndrome in children (MIS-C).To characterize mucocutaneous disease and its relation to clinical course among hospitalized patients with COVID-19 and MIS-C.Descriptive cohort study of prospectively and consecutively hospitalized eligible patients between May 11, 2020 and June 5, 2020.In COVID-19 patients, 4 of 12 (33%) had rash and/or mucositis, including erythema, morbilliform pattern, and lip mucositis. In MIS-C patients, 9 of 19 (47%) had rash and/or mucositis, including erythema, morbilliform, retiform purpura, targetoid and urticarial patterns, along with acral edema, lip mucositis, tongue papillitis, and conjunctivitis. COVID-19 patients with rash had less frequent respiratory symptoms, pediatric intensive care unit admission, invasive ventilation, and shorter stay versus COVID-19 patients without rash. MIS-C patients with rash had less frequent pediatric intensive care unit admission, shock, ventilation, as well as lower levels of C-reactive protein, ferritin, D-dimer, and troponin (vs MIS-C without rash). Neutrophil-to-lymphocyte ratio was similar for patients with and without rash in both groups. None of the MIS-C patients met criteria for Kawasaki disease.Small sample sizes.Mucocutaneous disease is common among children and adolescents with COVID-19 and MIS-C. Laboratory trends observed in patients with rash may prognosticate a less severe course.
2020Gastrointestinal and renal involvement in systemic vasculitis.Rev Esp Enferm DigVasculitis can also present with GI or solid organ involvement. IgA and ANCA associated vasculitis are more likely to have GI involvement. A 56-year-old female was admitted to the ER due to nausea, vomiting, epigastric pain and fever. The patient had a medical history of acromegaly and chronic kidney disease of an undetermined etiology, elevated C-reactive protein and renal dysfunction. Abdominal-CT revealed duodenal parietal thickening and pancreatic head edema. On esophagogastroduodenoscopy (EGD), duodenal mucosa had a diffusely nodular aspect with ulcerated areas. The following differential diagnosis were made, infectious enteritis, Whipple disease, infiltrative disorder and GI vasculitis. After discussion between a multidisciplinary team of Gastroenterology and Nephrology, they decided to initiate oral glucocorticoids due to worsening of the renal function, which lead to the resolution of digestive symptoms and renal function stabilization. Myeloperoxidase antineutrophilic-cytoplasmic antibodies (MPO-ANCA) were subsequently positive and histology confirmed duodenal involvement by vasculitis. The patient was asymptomatic after 4-weeks, with endoscopic healing and renal function stabilization. GI involvement limited to the duodenum in the setting of ANCA-MPO vasculitis is a rare condition. Moreover, histopathologic confirmation of vasculitis in endoscopic biopsy samples is exceptional.
2020Clinical characteristics of 10 children with a pediatric inflammatory multisystem syndrome associated with COVID-19 in Iran.BMC PediatrAlthough symptoms and signs of COVID-19 (Coronavirus disease 2019) in children are milder than adults, there are reports of more severe cases which were defined as pediatric inflammatory multisystem syndrome (PIMS). The purpose of this report was to describe the possible association between COVID-19 and PIMS in children.From 28 March to 24 June 2020, 10 febrile children were admitted with COVID-19 infection showing characteristics of PIMS in Buali tertiary hospital of Sari, in Mazandaran province, northern Iran. Demographic and clinical characteristics, laboratory and imaging findings, and therapeutic modalities were recorded and analyzed.The mean age of the patients was 5.37 ± 3.9 years (13 months to 12 years). Six of them were boys. Kawasaki disease, myocarditis, toxic shock syndrome, appendicitis, sepsis, urosepsis, prolonged febrile seizure, acute hemorrhagic edema of infancy, and COVID-19-related pneumonia were their first presentation. All of them had increased C-reactive protein levels, and most of them had elevated erythrocyte sedimentation rate, lymphopenia, anemia, and hypoalbuminemia. Three of them had thrombocytopenia(PLT < 10). Six of them were serologically or polymerase chain reaction positive for COVID-19, and 4 of them were diagnosed as COVID-19 just by chest computed tomography scan. Most of the patients improved without a residual sequel, except one who died with multiorgan failure and another case was discharged with a giant coronary aneurysm.Children with COVID-19 may present symptoms similar to Kawasaki disease and inflammatory syndromes. PIMS should be considered in children with fever, rash, seizure, cough, tachypnea, and gastrointestinal symptoms such as vomiting, diarrhea, and abdominal pain.
2020Phases of fluid management and the roles of human albumin solution in perioperative and critically ill patients.Curr Med Res OpinPositive fluid balance is common among critically ill patients and leads to worse outcomes, particularly in sepsis, acute respiratory distress syndrome, and acute kidney injury. Restrictive fluid infusion and active removal of accumulated fluid are being studied as approaches to prevent and treat fluid overload. Use of human albumin solutions has been investigated in different phases of restrictive fluid resuscitation, and this narrative literature review was undertaken to evaluate hypoalbuminemia and the roles of human serum albumin with respect to hypovolemia and its management.PubMed/EMBASE search terms were: "resuscitation," "fluids," "fluid therapy," "fluid balance," "plasma volume," "colloids," "crystalloids," "albumin," "hypoalbuminemia," "starch," "saline," "balanced salt solution," "gelatin," "goal-directed therapy" (English-language, pre-January 2020). Additional papers were identified by manual searching of reference lists.Restrictive fluid administration, plus early vasopressor use, may reduce fluid balance, but in some cases fluid overload cannot be entirely avoided. Deresuscitation, with fluid actively removed through diuretics or ultrafiltration, reduces duration of mechanical ventilation and intensive care unit stay. Combining hyperoncotic human albumin solution with diuretics increases hemodynamic stability and diuresis. Hyperoncotic albumin corrects hypoalbuminemia and raises colloid osmotic pressure, limiting edema formation and potentially improving endothelial function. Serum levels of albumin relative to C-reactive protein and lactate may predict which patients will benefit most from albumin therapy.Hyperoncotic human albumin solution facilitates restrictive fluid therapy and the effectiveness of deresuscitative measures. Current evidence is mostly from observational studies, and more randomized trials are needed to better establish a personalized approach to fluid management.
2020Prognostic impact of admission high-sensitivity C-reactive protein in acute myocardial infarction patients with and without diabetes mellitus.Cardiovasc DiabetolHigh-sensitivity C-reactive protein (hs-CRP) elevation frequently occurs in acute myocardial infarction (AMI) and is associated with adverse outcomes. Since diabetes mellitus (DM) is characterized by an underlying chronic inflammation, hs-CRP may have a different prognostic power in AMI patients with and without DM.We prospectively included 2064 AMI patients; hs-CRP was measured at hospital admission. Patients were grouped according to hs-CRP quartiles and DM status. The primary endpoint was a composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema. Two-year all-cause mortality was the secondary endpoint.Twenty-six percent (n = 548) of patients had DM and they had higher hs-CRP levels than non-DM patients (5.32 vs. 3.24 mg/L; P < 0.0001). The primary endpoint incidence in the overall population (7%, 9%, 13%, 22%; P for trend < 0.0001), in DM (14%, 9%, 21%, 27%; P = 0.0001), and non-DM (5%, 8%, 10%, 19%; P < 0.0001) patients increased in parallel with hs-CRP quartiles. The adjusted risk of the primary endpoint increased in parallel with hs-CRP quartiles in DM and non-DM patients but this relationship was less evident in DM patients. In the overall population, the adjusted OR of the primary endpoint associated with an hs-CRP value ≥ 2 mg/L was 2.10 (95% CI 1.46-3.00). For the same risk, hs-CRP was 7 and 2 mg/L in patients with and without DM. A similar behavior was observed for the secondary endpoint when the HR associated with an hs-CRP value ≥ 2 mg/L found in the overall population was 2.25 (95% CI 1.57-3.22). For the same risk, hs-CRP was 8 and 1.5 mg/L in DM and non-DM patients.This study shows that hs-CRP predicts in-hospital outcome and two-year mortality in AMI patients with and without DM. However, in DM patients, the same risk of developing events as in non-DM patients is associated to higher hs-CRP levels.
2020Patchy Vasoconstriction Versus Inflammation: A Debate in the Pathogenesis of High Altitude Pulmonary Edema.CureusHigh altitude pulmonary edema (HAPE) occurs in individuals rapidly ascending at altitudes greater than 2,500 m within one week of arrival. HAPE is characterized by orthopnea, breathlessness at rest, cough, and pink frothy sputum. Several mechanisms to describe the pathophysiology of HAPE have been proposed in different kinds of literature where most of the mechanisms are reported to be activated before a drop in oxygen saturation levels. The majority of the current studies favor diffuse hypoxic pulmonary vasoconstriction (HPV) as a pathophysiological basis for HAPE. However, some of the studies described inflammation in the lungs and genetic basis as the pathophysiology of HAPE. So, there is a major disagreement regarding the exact pathophysiology of HAPE in the current literature, which raises a question as to what is the exact pathophysiology of HAPE. So, we reviewed 23 different articles which include clinical trials, review articles, randomized controlled trials (RCTs), and original research published from 2010 to 2020 to find out widely accepted pathophysiology of HAPE. In our study, we found out sympathetic stimulation, reduced nitric oxide (NO) bioavailability, increased endothelin, increased pulmonary artery systolic pressure (PASP) resulting in diffuse HPV, and reduced reabsorption of interstitial fluid to be the most important determinants for the development of HAPE. Similarly, with the evaluation of the role of inflammatory mediators like C-reactive protein (CRP) and interleukin (IL-6), we found out that inflammation in the lungs seems to modulate but not cause the process of development of HAPE. Genetic basis as evidenced by increased transcription of certain gene products seems to be another promising hypoxic change leading to HAPE. However, comprehensive studies are still needed to decipher the pathophysiology of HAPE in greater detail.
2020Adjunct low level laser therapy (LLLT) in a morbidly obese patient with severe COVID-19 pneumonia: A case report.Can J Respir TherCOVID-19 poses a higher risk of complications in obese patients due to low respiratory system compliance, increased inflammatory cytokines, and an activated immune system secondary to excess adiposity. Low level laser therapy (LLLT) has significant anti-inflammatory effects and reduces inflammatory cytokines. It is noninvasive and approved for pain management and musculoskeletal injuries. Data from human and experimental animal models of respiratory tract disease suggests that LLLT reduces inflammation and promotes lung healing.A morbidly obese 32-year-old Asian female with severe COVID-19 received four consecutive once-daily LLLT sessions via a laser scanner. Pulsed 808 nm and 905 nm laser beams were delivered over the posterior chest for 28 min. The patient was evaluated before and after LLLT by radiological assessment of lung edema (RALE) on chest X-ray, oxygen requirements and saturation, pneumonia severity indices (SMART-COP and Brescia-COVID), blood inflammatory markers (interleukin-6, ferritin, and C-Reactive protein (CRP)). Prior to treatment, oxygen saturation (SpO) via pulse oximetry was 88%-93% on 5-6 L oxygen. Following LLLT, SpO increased to 97%-99% on 1-3 L oxygen. Reductions in RALE score from 8 to 3, Brescia-COVID from 4 to 0, and SMART-COP from 5 to 0 were observed. Interleukin-6 decreased from 45.89 to 11.7 pg/mL, ferritin from 359 to 175 ng/mL, and CRP from 3.04 to 1.43 mg/dL. Post-treatment, the patient noted appreciable improvement in respiratory symptoms.Following LLLT our patient showed improvement over a few days in respiratory indices, radiological findings, inflammatory markers, and patient outcomes. This report suggests that adjunct LLLT can be safely combined with conventional treatment in patients with severe COVID-19 and morbid obesity.
2020osteomyelitis of the distal radius in a healthy pregnant woman.J Bone Jt InfectAlthough characteristic, is a rare cause of osteomyelitis, especially in healthy individuals. A 25-year old primigravida at 29 weeks' gestation noticed pain and swelling in her right wrist. Her leukocyte count was normal, but her C-reactive protein level was slightly elevated, at 1.1 mg dL (normal range,  mg dL ). Plain radiography showed an osteolytic lesion in the distal radius, and magnetic resonance imaging (MRI) showed an extraosseous fluid collection with bone edema in addition to the osseous lesion. After a needle biopsy was performed, the skin overlying the lesion became ulcerated at the site of the needle tract. We drained whitish pus from the site; both this pus and the original biopsy specimen grew on culture. We diagnosed osteomyelitis and began intravenous antibiotic therapy, avoiding oral quinolones to prevent fetotoxicity. Her symptoms resolved, as did the bone edema and fluid collection. Ossification occurred at the site of osteolysis, with localized abnormal signal intensity persisting on MRI. This rare case of osteomyelitis was treated without surgery; the patient's pregnancy influenced the treatment course.
2020The Natural History of Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome in Children: A Systematic Review.J Pediatric Infect Dis SocThe clinical manifestations and natural history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related multisystem inflammatory syndrome in children (MIS-C) are poorly defined. Using a systematic review of individual cases and case series and collating elements of the clinical course, the objective of this study was to provide a detailed clinical description and natural history of MIS-C.Case reports and series of MIS-C were recovered from repeated MEDLINE searches, a single EMBASE search, and table of contents reviews of major general medicine and pediatric journals performed between June 3 and July 23, 2020. Fever, evidence of inflammation, and evidence of organ dysfunction were required for inclusion.MEDLINE and EMBASE searches produced 129 articles, and 10 articles were identified from journal contents or article bibliographies; 16 reports describing 505 children with MIS-C comprise this review. Thirty-two children (14.7%) had negative results for SARS-CoV-2 by nucleic acid and/or antibody testing. The weighted median age was 9 years (6 months to 20 years). Clinical findings included fever (100%), gastrointestinal symptoms (88.0%), rash (59.2%), conjunctivitis (50.0%), cheilitis/ "strawberry tongue" (55.7%), or extremity edema/erythema (47.5%). Median serum C-reactive protein, ferritin, fibrinogen, and D-dimer concentrations were above the normal range. Intravenous gammaglobulin (78.1%) and methylprednisolone/prednisone (57.6%) were the most common therapeutic interventions; immunomodulation was used in 24.3% of cases. Myocardial dysfunction requiring ionotropic support (57.4%) plus extracorporeal membrane oxygenation (5.3%), respiratory distress requiring mechanical ventilation (26.1%), and acute kidney injury (11.9%) were the major complications; anticoagulation was used commonly (54.4%), but thrombotic events occurred rarely (3.5%). Seven (1.4%) children died.MIS-C following SARS-CoV-2 infection frequently presents with gastrointestinal complaints and/or rash; conjunctivitis, cheilitis, and/or extremity changes also occur frequently. Serious complications occur frequently and respond to aggressive supportive therapy.
2020A case of anti-VEGF therapy application in Takayasu arteries with retinopathy.Am J Ophthalmol Case RepTakayasu arteritis (TA) is a systemic granulomatous large vessel vasculitis that involves mainly the aorta and its primary branches, and occurs most commonly in young females. Ocular manifestations of TA include small vessels dilation, microaneurysm, arteriovenous anastomosis, retinal ischemia and retinopathy. However, no specific and effective treatments for Takayasu retinopathy is applied. This case aimed to demonstrate the role of anti-VEGF (vascular endothelial growth factor) therapy in treating Takayasu retinopathy.We herein reported an 18-year-old Asian woman who presented with typical wreath-like arteriovenous anastomosis around the disc in the right eye and vitreous hemorrhage in the left eye. The stenosis and occlusion of bilateral subclavian arteries, carotid arteries and other proximal arteries on angiography confirmed the diagnosis of TA. Meanwhile, elevated ESR and CRP revealed that TA was in the active stage. We applied anti-VEGF therapy in treating Takayasu retinopathy specially to inhibit neovascularization. Additionally, vitreous extraction was conducted in the left eye after the treatment of anti-VEGF therapy.This is the first report of effective application of anti-VEGF therapy in inhibiting wreath-like arteriovenous anastomosis and improving vitrectomy in TA.
2020Acetabula Osteoid Osteoma Mimicking Juvenile Idiopathic Arthritis and Chronic Recurrent Multifocal Osteomyelitis.Case Rep RheumatolOsteoid osteoma (OO) is a benign bone tumor that usually presents between 10 and 35 years of age. The metaphysis and diaphysis of the femur and tibia are the typical locations. The diagnosis is usually straightforward when images reveal a radiolucent nidus surrounded by reactive sclerosis. However, the diagnosis is more difficult when it occurs at atypical locations with nonspecific and misleading appearance on images. OO may mimic juvenile idiopathic arthritis (JIA), bone infection, or malignancy. We present a 14-year-old male with a 4-month history of left hip pain. His pain was worse with playing hockey and lacrosse and in the morning and sometimes woke him up at night. His examination was significant for pain with flexion and external rotation of the left hip and for mild limitation of full external rotation. Blood work revealed normal complete blood count, erythrocyte sedimentation rate, and C-reactive protein. Left hip X-ray was unremarkable. Left hip MR arthrogram showed marked edema of the medial and posterior walls of the left acetabulum. CT-guided biopsy of the left acetabulum showed unremarkable flow cytometry and chronic inflammatory component raising concern about chronic recurrent multifocal osteomyelitis (CRMO). Bone scan revealed focal increased uptake in the left acetabulum and no additional abnormality. Repeat MRI with intravenous contrast showed a left hip effusion, focal synovial enhancement in the medial left hip, and acetabula edema. The patient failed treatment for presumed JIA and CRMO with nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, methotrexate, and adalimumab. CT scan of the left hip was performed for further evaluation of the bone and showed 11 × 6 mm low attenuation focus with subtle internal nidus in the posteromedial aspect of the acetabular rim, suggestive of intra-articular OO. Radiofrequency ablation was performed with no complications, and the left hip pain improved. The atypical location resulted in delay of diagnosis for 12 months after presentation. We highlight the diagnostic pitfalls observed in atypical OO locations and the difficulties this creates with making the diagnosis. OO mimicking JIA has previously been described. We submit CRMO as another differential diagnosis which may be mimicked and demonstrate the vital role of CT scan in the diagnosis.
2021Diffusion-Weighted MRI to Assess Sacroiliitis: Improved Image Quality and Diagnostic Performance of Readout-Segmented Echo-Planar Imaging (EPI) Over Conventional Single-Shot EPI.AJR Am J RoentgenolPlease see the Editorial Comment by Ricardo Donners discussing this article. DWI using single-shot echo-planar imaging (ss-EPI) is prone to artifacts, signal-intensity dropout, and T2* blurring. Readout-segmented echo-planar imaging (rs-EPI) may improve image quality in DWI of the sacroiliac joints. The purposes of this study were, first, to qualitatively and quantitatively compare image quality between ss-EPI and rs-EPI DWI of the sacroiliac joints; and, second, to evaluate whether ADC values derived from ss-EPI and rs-EPI can differentiate disease activity in patients with axial spondyloarthritis (axSpA). This retrospective study included 75 patients who underwent ss-EPI and rs-EPI DWI of the sacroiliac joints. Patients were classified into axSpA ( = 50) and no-ax-SpA ( = 25) groups on the basis of Assessment of SpondyloArthritis International Society (ASAS) criteria. Patients in the axSpA group were assigned to one of four disease activity states using the Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP). Two radiologists independently assessed qualitative (overall image quality and diagnostic confidence) and quantitative (ADC, signal-to-noise ratio [SNR], and contrast-to-noise ratio [CNR]) imaging parameters. Readout-segmented EPI provided significantly better overall image quality, diagnostic confidence, SNR, and CNR than ss-EPI (both readers, < .001). In patients with axSpA, the correlation coefficients () of ADC values and ASDAS-CRP values were 0.456 and 0.458 for ss-EPI and 0.537 and 0.558 for rs-EPI. ADCs showed progressive increases with increasing activity state for both sequences, although these increases were more substantial for rs-EPI than for ss-EPI. Across readers, median ADCs for ss-EPI were 0.243 and 0.234 × 10 mm/s for inactive disease, 0.411 and 0.412 × 10 mm/s for moderate disease activity, 0.499 and 0.447 × 10 mm/s for high activity, and 0.671 and 0.575 × 10 mm/s for very high activity (reader 1, = .011; reader 2, = .010). Across readers, ADCs for rs-EPI were 0.236 and 0.236 × 10 mm/s for inactive disease, 0.483 and 0.477 × 10 mm/s for moderate disease activity, 0.727 and 0.692 × 10 mm/s for high activity, and 0.902 and 0.803 × 10 mm/s for very high activity (reader 1, = .002; reader 2, = .001). ADC values for ss-EPI were significantly different only between the inactive and very high disease activity groups ( < .0083, Bonferroni-corrected threshold). ADC values for rs-EPI were significantly different between the inactive and high, inactive and very high, as well as the moderate and very high disease activity groups ( < .0083, Bonferroni-corrected threshold). Readout-segmented EPI significantly improves the image quality of DWI in imaging the sacroiliac joints. In patients with axSpA, activity states are better differentiated by rs-EPI than by ss-EPI. Readout-segmented EPI is a more robust tool than ss-EPI for imaging of axSpA and should be included in routine clinical protocols for MRI of the sacroiliac joints.
2020Severe neck pain and odynophagia secondary to acute calcific longus colli tendinitis: a case report.J Med Case RepAcute calcific longus colli tendinitis is a rare, noninfectious inflammatory condition caused by the deposition of calcium crystals. The condition is self-limiting, yet commonly misdiagnosed. Here we report a case of a patient with severe neck pain and odynophagia initially misdiagnosed as a retropharyngeal abscess before establishing the correct diagnosis of acute calcific longus colli tendinitis.A 60-year-old Caucasian man presented to an outside emergency department with a 5-day history of neck pain and odynophagia. The neck pain was severe and aggravated by movement. Laboratory evaluation revealed leukocytosis and elevated C-reactive protein. Computed tomography of his neck soft tissues was initially interpreted as a retropharyngeal abscess. Antibiotic therapy with piperacillin/tazobactam was initiated, and the patient was transferred to our tertiary care center for further evaluation and treatment. On physical examination, the patient's neck range of motion was significantly diminished, and bilateral neck tenderness was present. An otolaryngologist performed an examination with laryngoscopy, the result of which was unremarkable. A radiologist at our facility interpreted his outside magnetic resonance imaging as showing "calcification in the prevertebral muscles at C1-C2, inflammation with edema of the prevertebral muscles, and retropharyngeal space edema/effusion," consistent with acute calcific longus colli tendinitis. His antibiotics were discontinued, and he was started on intravenous ketorolac. He had significant improvement in his neck range of motion, and his pain diminished greatly. He was discharged on a 10-day course of diclofenac (50 mg three times daily). At 1-week follow-up, the patient was doing well; he had returned to work, and his pain was well controlled.This case report details the presentation, characteristic radiographic findings, and management of a patient with an extremely rare condition of neck pain and odynophagia that could be treated with nonsteroidal anti-inflammatory drugs.
2020Paraneoplastic Dermatomyositis in a Patient with Metastatic Gastric Carcinoma.Acta Dermatovenerol CroatDear Editor, Paraneoplastic dermatomyositis is a distinct clinical variant of dermatomyositis (DM) in which the typical cutaneous features and muscle weakness appear before, simultaneously, or after the diagnosis of an internal malignancy. It occurs in approximately one-third of patients with DM, predominantly adults, after the age of 40 (1). Different neoplasms have been described in association with DM, the most common of which are lung, breast, ovarian, gastrointestinal, prostate, and bladder cancers. The gender distribution of cancer type corresponds roughly to that of the general population (1,2). We report the case of a 58-year-old man who presented with facial heliotrope erythema, periorbital edema, Gottron's papules over the interphalangeal and metacarpophalangeal joints, and Gottron's sign on the elbows (Figure 1). The patient also exhibited some less frequent skin signs of DM, such as shawl sign on the upper back and shoulders and V-sign on the neck and chest. Apart from the rash, he complained of weight loss, adynamia, dysphagia, cough, and scant expectoration, which he reported experiencing over a 3-month period. The muscle involvement consisted of proximal muscle weakness and had appeared a month after the skin rash. The histology of the skin lesion revealed epidermal atrophy, vacuolar degeneration of the basal keratinocytes, and perivascular and periadnexal lymphocytic infiltrate in the upper dermis (Figure 2). Laboratory examination found increased creatine kinase (2822 U/L) and liver enzymes, anemia, and leukocytosis. Screening for antinuclear antibodies and anti-Jo1 autoantibodies were both negative. The diagnosis of trichinosis was excluded via serologic examination. The impaired general condition of the patient led to a prompt paraneoplastic screening. Abdominal sonography detected hepatomegaly. Computed tomography (CT) of the abdomen and pelvis visualized a mass in the distal part of the esophagus, narrowed lumen of the gastric cardia, enlarged gastric lymph nodes, lung and liver metastases, and ascites (Figure 3). The diagnosis of paraneoplastic DM in association with an advanced, metastatic, primary gastric carcinoma was established. Palliative surgery and chemotherapy were proposed to the patient, but he refused both. A systemic therapy with methylprednisolone 60 mg/daily and azathioprine 100 mg/daily was initiated, aiming to alleviate the progressively worsening muscle weakness, but proved ineffective. The patient died two months later of combined respiratory and heart failure. There are multiple prediction factors, such as cutaneous signs, laboratory data, and disease progression, which may direct the physician towards the possibility of paraneoplastic DM. Some atypical cutaneous lesions, such as cutaneous necrosis or vasculitis, hyperkeratotic follicular papules, vesiculo-bullous lesions, and flagellate erythema, are seen more frequently in cancer-associated DM (3,4). None of these were present in our patient. Pruritus is also described as a paraneoplastic sign (5). Some authors consider the increased erythrocyte sedimentation rate and C-reactive protein to be of predictive value for malignancy. Myositis-specific autoantibodies anti-TIF1-γ and anti-NXP-2, among the numerous novel serological markers for DM, are clearly associated with the presence of neoplasia (6,7). Unfortunately, we were unable to test for those autoantibodies. The symptom of dysphagia is a hallmark of paraneoplastic dermatomyositis and usually represents a manifestation of muscle weakness (8). In our case, it was rather a reflection of the endoluminal tumor, although it may also be a combination of both factors. In their study, Bowerman et al. investigated the risk of cancer development in different DM subtypes (9). They included 201 patients with adult-onset DM, 142 of with classic DM and 59 with the clinically amyopathic type. The estimated prevalence of malignancy-associated classic and clinically amyopathic DM were 9.9% and 1.7%, respectively. The authors concluded that older age and classic DM represent independent risk factors for malignancy-associated DM within 2 years of disease onset. Given that early diagnosis significantly impacts prognosis in patients with cancer-associated DM, recent studies support blind screening for internal malignancy (10). Leatham et al. performed a retrospective analysis of 400 patients with DM, finding a total of 53 cancers in 48 patients (some of the patients had two separate neoplasms). Among the group of paraneoplastic DM cases, 17 cancers were diagnosed via purely blind screening in patients with a lack of concerning history or physical examination. The authors claimed that the most informative tests were mammography and CT scanning. The above-mentioned predictive factors for paraneoplastic DM represent a useful tool for the clinician. Although it is generally accepted that patients with DM should undergo some type of cancer screening, there is no consensus regarding methods or frequency. New data suggest that blind screening in asymptomatic patients might be of great importance for early diagnosis and treatment of patients with cancer-associated DM.
2021Clinical and computed tomography factors associated with sepsis in women with clinically uncomplicated pyelonephritis.Abdom Radiol (NY)Sepsis is major determinants of prognosis in acute pyelonephritis (APN). This study aimed to assess factors associated with the development of sepsis among patients with clinically uncomplicated APN.We examined 463 patients presenting to our hospital without complications. We assessed clinical factors including demographic and laboratory features. Renal and extrarenal features on computed tomography (CT) were also analyzed. Risk factors of sepsis are assessed.The study included 361 patients without (78.0%) and 102 patients with sepsis (22.0%). Crude and attributable mortality rates were 3.9% and 2.0% versus 1.4% and 0.6%, respectively, among patients with and without sepsis. Clinical risk factors for sepsis were age >65 years (odds ratio [OR] 1.79, P = 0.02), absence of flank pain (OR 1.59, P = 0.04), absence of costovertebral tenderness (OR 1.89, P = 0.03), diabetes mellitus (OR 2.25, P = 0.02), bacteremia (OR 2.8, P = 0.01), C-reactive protein level >100 mg/L (OR 1.42, P = 0.02), and lack of previous APN history (OR 1.76, P = 0.04). APN grade IV (OR 3.16, P = 0.01), high grade hydronephrosis (OR 1.50, P = 0.03), diffuse peritoneal thickening (OR 4.12, P = 0.01), and acute interstitial pulmonary edema (OR 3.73, P = 0.01) were the CT features predictive of septic shock.Although uncomplicated APN was largely non-fatal, several clinical and CT features could lead to sepsis. Our findings may be useful for predicting sepsis risk and deciding whether intravenous antibiotic treatment and intensive management should be initiated for uncomplicated APN.
2020The effect of intraoperative goal-directed crystalloid versus colloid administration on perioperative inflammatory markers - a substudy of a randomized controlled trial.BMC AnesthesiolExcessive perioperative fluid administration may result in iatrogenic endothelial dysfunction and tissue edema, transducing inflammatory markers into the bloodstream. Colloids remain longer in the circulation, requiring less volume to reach similar hemodynamic endpoints compared to crystalloids. Thus, we tested the hypothesis that a goal-directed colloid regimen attenuates the inflammatory response compared to a goal-directed crystalloid regime.Patients undergoing moderate- to high-risk open abdominal surgery were randomly assigned to goal-directed lactated Ringer's solution (n = 58) or a hydroxyethyl starch 6% 130/0.4 (n = 62) fluid regimen. Our primary outcome was perioperative levels of pro- and anti-inflammatory cytokines. Secondary outcome was perioperative levels of white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT) and lipopolysaccharide-binding protein (LBP). Measurements were performed preoperatively, immediate postoperatively, on postoperative day one, two and four.The areas under the curve of Interleukin (IL) 6 (p = 0.60), IL 8 (p = 0.46), IL 10 (p = 0.68) and tumor necrosis factor α (p = 0.47) levels did not differ significantly between the groups. WBC, CRP and PCT values were also comparable. LBP, although significantly higher in the crystalloid group, remained in the normal range. Patients assigned to crystalloids received a median (IQR) amount of 3905 mL (2880-5288) of crystalloid. Patients assigned to colloids received 1557 mL (1207-2116) of crystalloid and 1250 mL (750-1938) of colloid.Cytokine and inflammatory marker levels did not differ between goal-directed crystalloid and colloid administration after moderate to high-risk abdominal surgery.ClinicalTrials.gov ( NCT00517127 ). Registered 16th August 2007.
2020Neutralization of the edema-forming and myotoxic activities of the venom of Potamotrygon motoro Müller and Henle, 1841 (Chondrichthyes - Potamotrygoninae) by antivenoms and circulating immunoglobulins.ToxiconFreshwater stingrays are cartilaginous fish with stingers at the base of their tail. The stinger is covered with an epithelium containing mucous and venom glands. Human envenomation usually occurs when a person steps on a stingray hiding in the sand and the fish sinks its stinger into the victim, causing an extremely painful wound which generally leads to tissue necrosis. Medical treatment is based on the use of painkillers, anti-inflammatory drugs and antibiotics, as there is to date no specific antidote for envenomation by freshwater stingrays. The aim of this study was therefore to investigate whether sera containing anti-P. motoro antibodies can neutralize the edema-forming and myotoxic activities of Potamotrygon motoro venom. To this end, two protocols were used: seroneutralization and vaccination of mice. The seroneutralization protocol involved intramuscular injection of the P. motoro venom in the mice gastrocnemius followed by administration of hyperimmune mouse serum anti P. motoro dorsal extract and stinger extract via the ophthalmic venous plexus. The vaccination protocol involved immunizing the mice with dorsal or stinger extract adsorbed to aluminum hydroxide followed by intramuscular challenge with the P. motoro venom. The gastrocnemii of all the animals were removed for histopathological and stereological analyses, and blood was collected via the ophthalmic venous plexus to measure IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF, C-reactive protein and total creatine kinase. Protocols did not neutralize the edema-forming or local myotoxic induced by P. motoro venom under the experimental conditions tested. But systemic rhabdomyolysis was only completely neutralized in animals vaccinated with the stinger extract. Cytokine analysis revealed that under the experimental conditions used here, seroneutralization induced release of Th1, Th2, Th17 and Treg cytokines whereas vaccination induced a Th1 response.
2020[Does hypoalbuminemia contribute to the worsening of heart failure?]Ann Cardiol Angeiol (Paris)Hypoalbuminemia has now emerged as a powerful prognosticator in heart failure regardless of age, clinical presentation, left ventricular ejection fraction and usual prognostic markers. Growing evidence is that this prognostic value persists after adjusting for causative factors for hypoalbuminemia such as malnutrition, inflammation and liver dysfunction.To address the prognostic relevance of hypoalbuminemia in frail elderly patients with well-characterized cardiogenic pulmonary edema at high risk for adverse outcome, beyond causative factors for low serum albumin levels. Serum albumin was measured after clinical stabilization to avoid hypervolemia.In all, 67 patients with a mean age of 86 years were included. Hospital mortality was 30%. Patients who died and who survived were similar in age, ejection fraction, BNP concentration, serum creatinine, serum hemoglobin, total bilirubin and prealbumin. Patients who died had lower serum albumin levels (P<0.001), higher blood urea nitrogen (P=0.03) and higher C-reactive protein (P=0.02). In multivariate analysis, serum albumin was the sole independent predictor of hospital death (P<0.01), after adjusting for malnutrition (prealbumin P=ns), inflammation (C-reactive protein P=ns) and liver dysfunction (total bilirubin P=ns).Serum albumin is a powerful prognosticator in frail elderly patients with acute cardiogenic pulmonary edema even after adjusting for main causative factors. These results suggest that hypoalbuminemia may contribute to the worsening of heart failure given the physiological properties of serum albumin that includes antioxidant activity and plasma colloid osmotic pressure action. Further studies are critically needed to address the relevance of prevention and correction of hypoalbuminemia in heart failure.
2020Phytosome Loading the Combined Extract of Mulberry Fruit and Ginger Protects against Cerebral Ischemia in Metabolic Syndrome Rats.Oxid Med Cell LongevThe prevalence of ischemic stroke in metabolic syndrome (MetS) is continually increasing and produces a great impact on both qualities of life and annual healthcare budget. Due to the efficiency limitation of the current therapeutic strategy, the poor availability of polyphenol substances induced by the first pass effect and the beneficial effects of mulberry fruit and ginger on brain and MetS-related diseases together with the synergistic concept, the neuroprotective effect against ischemic stroke in MetS condition of phytosome containing the combined extract of mulberry fruit and ginger (PMG) has been considered. To explore the neuroprotective effect and possible underlying mechanism of PMG on brain damage in cerebral ischemic rat with MetS, male Wistar rats were induced MetS by high-carbohydrate high-fat diet (HCHF) for 16 weeks and subjected to the cerebral ischemia/reperfusion injury (CIRI) at the right middle cerebral artery (Rt. MCAO). PMG at doses of 50, 100, and 200 mg/kg were orally fed with for 21 days, and they were assessed brain damage, neurological deficit score, and the changes of oxidative stress markers, inflammatory markers, PPAR expression, and epigenetic modification via DNMT-1 were performed. All doses of PMG significantly improved brain infarction, brain edema, and neurological deficit score. In addition, the reduction in DNMT-1, MDA level, NF-B, TNF, and C-reactive protein together with the increase in SOD, CAT, and GPH-Px activities, and PPAR expression in the lesion brain were also observed. The current data clearly revealed the neuroprotective effect against cerebral ischemia with MetS condition. The possible underlying mechanism might occur partly via the suppression of DNMT-1 giving rise to the improvement of signal transduction via PPAR resulting in the decreasing of inflammation and oxidative stress. In conclusion, PMG is the potential neuroprotectant candidate against ischemic stroke in the MetS condition. However, the clinical trial is still essential.
2020The Anti-Inflammatory Effect of Different Doses of Aliskiren in Rat Models of Inflammation.Drug Des Devel TherThe present study was designed to evaluate the anti-inflammatory effects of different doses of aliskiren in two animal models of inflammation.Sixty-six Wistar rats were allocated into five groups: the first group (six rats) was treated with the vehicle only, without induction of paw edema and granulomatous inflammation, and served as a negative control; the second group (12 rats) was allocated into two subgroups and treated with the vehicle only, with induction of paw edema and granulomatous inflammation, and served as a positive control; the third group (36 rats) was allocated into six subgroups and treated with different doses of aliskiren (15, 30, and 60 mg/kg) in both models; the fourth group (12 rats) was treated with dexamethasone (1 mg/kg) in both models of inflammation. Serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1), and high sensitivity C-reactive protein (hs-CRP) were measured. Skin samples were also sent for histopathological examination.Aliskiren, in a dose-dependent pattern, significantly decreased inflammation in rat models of inflammation, by attenuating the percentage of exudate, granuloma, and paw edema. Furthermore, it significantly reduced serum concentrations of TNF-α, VCAM-1, and hs-CRP and restored the serum concentration of IL-10. Additionally, significant improvement was seen in the histopathological findings.In the current study, aliskiren was successful in decreasing inflammation in both models. These findings suggest that aliskiren is a good candidate for the treatment of inflammatory diseases.
2020Prevalence and Management of Severe Hand, Foot, and Mouth Disease in Xiangyang, China, From 2008 to 2013.Front PediatrTherapeutic strategies for severe hand, foot, and mouth disease (HFMD) are currently either inconsequent or deficient in evidence. We retrospectively surveyed HFMD outbreaks in Xiangyang from June 2008 to December 2013. HFMD is staged from I to V according to clinical severity. Severe HFMD is defined as a case involving the central nervous system (CNS). We analyzed risk factors for fatality of severe cases and compared the efficiency and outcome of some therapies by binary logistic regression. The overall HFMD cases included 637 (1.26%) severe cases and 38 fatalities (0.075%). Analyses indicate that age (<3 years), enterovirus 71 (+), autonomic nervous system dysregulation, pulmonary edema/hemorrhage, C-reactive protein (CRP) (>40 mg/L), and cardiac troponin I (>0.04 ng/ml) are risk factors for fatality (all < 0.05). Intravenous immunoglobulin (IVIG) and mechanical ventilation applied only in early stage IV significantly improved HFMD progression (both < 0.05) with odds ratios of 0.24 (95% CI: 0.10-0.57) and 0.01 (95% CI: 0.00-0.10), respectively. Neither methylprednisolone nor milrinone administered in any stage made any significant difference on mortality (all > 0.05). Precise recognition of the severe HFMD cases in early stage IV and prompt IVIG and mechanical ventilation application may reduce mortality. Mechanical ventilation training programs and dispatch of specialists to hospitals where there is no chance of transferring critical cases to the severe HFMD designated hospitals are two key measures to reduce fatality.
2020Monckeberg Medial Calcific Sclerosis of the Temporal Artery Masquerading as Giant Cell Arteritis: Case Reports and Literature Review.CureusMonckeberg medial calcific sclerosis (MCS) is an infrequent finding in the temporal artery and can clinically present almost indistinguishably from giant cell arteritis (GCA). To our knowledge, there have been only two case reports of suspected GCA found to be MCS only after a temporal artery biopsy (TAB). Herein, we present two cases. The first case is a 69-year-old female with hypertension, type-2 diabetes mellitus, and chronic headaches who presented with left temporal headaches and scalp tenderness. She had a prominently dilated, tortuous, and tender left temporal artery. Initial labs showed a leukocyte count of 11.1x10/L, erythrocyte sedimentation rate (ESR) of 29 mm/hr, and C-reactive protein (CRP) of 5.8 mg/L. The patient was started on prednisone 60 mg for presumptive GCA. Left TAB was negative for inflammatory changes, with findings consistent with MCS. Steroids were discontinued, and symptoms resolved. The second case is a 67-year-old male with hypertension, asthma, hyperlipidemia, status-post left eye cataract phacoemulsification, with intraocular lens insertion one-month prior, who presented with left eye blurriness in the inferior visual field and intermittent headache for 15 days. Left ophthalmoscopy showed retinal pallor and edema. Initial labs revealed ESR of 25 mm/hr, CRP of 11.2 mg/L, leukocyte count of 13.01x10/L. The patient was given solumedrol 120 mg once and prednisone 70 mg daily for presumptive GCA. Left TAB was negative for GCA but reported damaged elastic fibers by calcification consistent with MCS. Partial visual blurriness remained, and steroids were discontinued. This report accentuates the importance of MCS as a temporal GCA simulator. Physicians should be aware that TAB potentially changes management and may help surface underlying conditions.
2020Schmorl Node-A Cause of Acute Thoracic Pain: A Case Report and Pathophysiological Mechanism.Int J Spine SurgWe report a case of a patient with an acute symptomatic Schmorl node (SN) that spontaneously resolved with characteristic imaging findings. The extensive hematological investigations also allow some insight as to the likely pathophysiology of the painful lesion.Case report of an acute symptomatic SN.A fit and athletic 44-year-old female participant in a competitive paddling event developed atypical thoracic pain and was admitted for further investigation. Normal blood results included complete blood cell count, clotting, and D-dimer. Creatine phosphokinase was 63 U/L (reference < 167 U/L) and troponin I levels were not raised. Her only hematological abnormality was an elevated C-reactive protein (CRP) at 60.2 mg/L (reference < 5 mg/L). Magnetic resonance imaging (MRI) scan showed signal hyperintensity involving T7 vertebral body, surrounding an enlarged SN. Patient was given oral nonsteroidal anti-inflammatory drugs, opioid analgesia, and gradually mobilized. After 3 days, the pain had sufficiently subsided and CRP was 17.8 mg/L. Follow-up MRI scan showed some reduction in the T2 hyperintensity and size of the intraosseous herniation. Patient gradually returned to full activities and had no recurrence of symptoms. MRI scan 8 months after the initial scan showed almost complete resolution of the T2 hyperintensity and pan-vertebral marrow edema.Symptomatic SN should be part of the differential diagnosis of unexplained thoracolumbar pain. Modality of choice for diagnosis would be MRI. Once diagnosed, several treatment options are available with the most likely being spontaneous resolution of symptoms and bone healing within a few months. The conservative approach is recommended when the symptoms can be medically well controlled.
2020Multiple brain abscesses with good prognosis in an infant with cyanotic congenital heart disease: a case report.J Med Case RepBrain abscesses are relatively rare, but they are a potentially life-threatening condition. Predictive factors for poor outcome are a young age and the presence of multiple abscesses. We report a case of a 15-month-old girl with cyanotic congenital heart disease who developed multiple brain abscesses caused by Streptococcus intermedius. The patient was treated with a combination of surgical aspiration and antimicrobial therapy without apparent neurological sequelae. To the best of our knowledge, this is the youngest such patient to have been reported in the literature. We explore the possible causes of her good outcome.At the age of 15 months, the Japanese patient initially was presented to our hospital with transient eye deviation to the left and vomiting. In a blood examination, her white blood cell count (12,720 per mm with a left shift) and C-reactive protein level (1.23 mg/ml) were slightly elevated. Magnetic resonance imaging of the brain showed three mass lesions. These were 1.5-cm, 1.9-cm, and 1.2-cm rim-enhancing lesions with extensive surrounding edema. Brain abscesses were diagnosed, and vancomycin (50 mg every 12 hours) and meropenem (40 mg every 8 hours) were started empirically. However, because each brain abscess was enlarged at 8 days after admission, surgical aspiration was performed at 10 days after admission, and cultures of the aspirated pus grew S. intermedius. Penicillin G (0.7 million units every 4 hours) and ceftriaxone (280 mg every 12 hours), to which this isolate is susceptible, were then administered, and the brain abscesses reduced in size. After 1 month of ceftriaxone and 3 months of penicillin G treatment, all of the brain abscesses disappeared. Apparent neurological sequelae were not observed at 6 months after onset.A good outcome can be obtained if multiple brain abscesses develop in infancy or early childhood in cases without unconsciousness at admission, meningitis, or sepsis. Appropriate antimicrobial therapy should be started immediately after diagnosis, with surgical aspiration performed to identify the causative pathogen and avoid intraventricular rupture of the brain abscesses.
2020Identification of risk factors for open conversion from laparoscopic cholecystectomy for acute cholecystitis based on computed tomography findings.Surg TodayLaparoscopic cholecystectomy (LC) is performed widely for acute cholecystitis (AC). This study was conducted to identify the predictors for conversion cholecystectomy (CC) for AC.The subjects of this study were 395 patients who underwent emergency surgery for AC between 2011 and 2019. Univariate and multivariate analyses were performed to establish the significance of the risk factors for CC in patients with grades II and III AC.There were 162 TG18 GII and GIII patients in the LC group and 31 in the CC group. Univariate analysis revealed significant differences in performance status (p = 0.039), C-reactive protein levels (p = 0.016), albumin levels (p = 0.002), gallbladder (GB) wall thickness (p = 0.045), poor contrast of the GB wall (p = 0.035), severe inflammation around the GB (p < 0.001), enhancement of the liver bed (p = 0.048), and duodenal edema (p < 0.001) between the groups. Multivariate analysis identified hypoalbuminemia (p = 0.043) and duodenal edema (p = 0.014) as independent risk factors for CC.Most patients with grade I AC underwent LC and had better surgical outcomes than those with grades II and III AC. The most appropriate surgical procedure should be selected based on preoperative imaging of the GB and the neighboring organs and by the presence of hypoalbuminemia.
2020The correlation between follow-up MRI findings and laboratory results in pyogenic spondylodiscitis.BMC Musculoskelet DisordAlthough MRI is the gold-standard imaging method in the diagnosis of spondylodiscitis, role of follow-up imaging is debated and there can be discrepancies with regard to the significance of bony or soft tissue responses to treatment. Purpose of our study is to test whether the MRI changes on follow-up imaging correlate with laboratory findings of treatment response.A total of 48 patients with pyogenic spondylodiscitis who underwent baseline and follow-up MRI were retrospectively reviewed. The extent of bone marrow edema, paravertebral soft tissue inflammation, and disc height were compared on baseline and follow-up MRIs with the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels obtained from the medical records at baseline and on follow-up. Relationships between the MRI and laboratory changes were analyzed using the Spearmann correlation test.The mean MRI follow-up period was 42.25 days. Based on the CRP (resolved: n = 19, resolving: n = 19, and aggravated: n = 10), there was significant correlation between the laboratory results and the changes in the bone and soft tissues (p < 0.01, both). The correlation was best with soft tissue changes (rho: 0.48) followed by bony changes (rho: 0.41). Based on the ESR (resolved: n = 8, resolving: n = 22, and worsened: n = 18), the correlation was stronger with bone changes (rho: 0.45, p < 0.01) than it was with soft tissue changes (rho: 0.39, p = 0.01).Follow-up MRI findings of pyogenic spondylodiscitis show variable tissue responses. CRP was best correlated with soft tissue changes, while ESR showed the best association with bony changes.
2020Diagnostic markers for community-acquired pneumonia.Ann Transl MedCommunity-acquired pneumonia (CAP) is one of the respiratory infectious diseases caused by not only bacteria, but also viruses. Antibiotic agents are needed to treat only bacterial but not viral CAP. In addition, there are some non-infectious respiratory diseases in the differential diagnosis of CAP, such as malignant diseases, interstitial lung diseases, pulmonary edema, and pulmonary hemorrhage. We usually diagnose patients having CAP by comprehensive evaluation of symptoms, vital signs, laboratory examinations, and radiographic examinations. However, symptoms and vital signs are not specific for the diagnosis of CAP; therefore, we also use inflammatory biomarkers for differentiating bacterial from viral CAP and non-infectious respiratory diseases. We have used the white blood cell count, C-reactive protein (CRP), and erythrocyte sedimentation rate as common inflammatory biomarkers, but they are not specific for bacterial infection because they could be increased by malignant diseases and collagen diseases. Recently, some inflammatory biomarkers such as procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), pro-adrenomedullin (proADM), and presepsin have been developed as relatively specific biomarkers for bacterial infection. Many reports have evaluated the usefulness of PCT for diagnosing CAP. In this review, the characteristics of each biomarker are discussed based on previous studies.
2020[Gut microbiota and systemic inflammation in patients with chronic heart failure].KardiologiiaAim To study the interrelationship between intensity of chronic systemic inflammation (CSI) with severity of the condition and intestinal microbiocenosis parameters in patients with chronic heart failure (CHF).Material and methods 47 hospitalized patients with symptomatic CHF were evaluated. The following parameters were determined: clinical condition; N-terminal pro-B-type natriuretic peptide (NT-proBNP). C-reactive protein (CRP); serum interleukins (IL) 6 and 10; and intestinal microbiocenosis composition by mass-spectrometry of microbial markers in whole blood. Microbiocenosis indexes were compared in the main group and in 38 outpatient patients with arterial hypertension and ischemic heart disease without CHF.Results Direct, medium-power correlations were found between CRP and IL-6 concentrations and severity of clinical condition (NT-proBNP, ХСН stage, and edema severity) in patients with CHF. Most patients with CHF had lower numbers of bifido-, lacto-, propionic-, and eubacteria, and Clostridium (С.) ramosum and higher numbers of aspergillus. Among CHF patients, the highest indexes of endotoxemia, gram (-) bacteria, cocci, actinomycetes, and microfungi were observed in the group with NT-proBNP from 400 to 2000 pg/ml. Direct correlations were observed for amounts of C. hystolyticum, Pseudonocardia spp., and Aspergillus spp. with IL-6 and IL-10 and unidirectional inverse correlation were observed for these cytokines with Propionibacterium acnes and jensenii, Streptomyces spp., and Nocardia asteroides. In addition, IL-6 concentration was negatively correlated with contents of Staphylococcus aureus, C. difficile, C. ramosum, Eggerthella lenta, and Corynebacterium spp. and was positively correlated with C. propionicum, Moraxella spp. and Flavobacterium spp. Concentration of IL-6 directly correlated with the number of Eubacterium spp. and inversely correlated with numbers of Ruminicoccus spp. and Streptomyces farmamarensis. The amount of Streptomyces farmamarensis negatively correlated with CRP concentrations.Conclusion The study results evidence the significance of intestinal microbial-tissue complex in the pathogenesis of CSI in CHF and allow suggesting this complex as a promising target for therapy.
2020Leukocytoclastic Vasculitis: An Early Skin Biopsy Makes a Difference.CureusLeukocytoclastic vasculitis (LCV) is an uncommon condition with a broad differential diagnosis. Although the clinical history, physical examination, and laboratory workup are pivotal when formulating a differential diagnosis of LCV, a skin biopsy is required in most cases to elucidate the cause. The diagnostic yield of a skin biopsy increases within the first 24 to 48 hours of the lesion onset indicating the importance of obtaining a prompt skin sample. We present the case of a 60-year-old man who presented to the emergency department with a three-day history of fevers, headaches, and a painful skin rash. He endorsed rhinorrhea and sore throat a week ago. Physical examination was notable for an erythematous papular rash with palpable violaceous purpura located mainly at the distal right leg and thigh. He also complained of painful bilateral hand edema. His complete blood count and chemistries were unremarkable. His C-reactive protein was 147 mg/L (normal value <8 mg/L), and sedimentation rate was 51 mm (normal value <15 mm). Immunoglobulin A was 509 mg/dL (normal value 82-460 mg/dL). Further workup including viral hepatitis serologies, antinuclear antibodies, complements, antineutrophil cytoplasmic antibodies, cryoglobulins, rheumatoid factor, and blood cultures yielded negative results. Therefore, it was believed that his rash was likely associated with his recent upper respiratory infection. A skin biopsy done on the first day of admission was positive for LCV without immunoglobulin A deposition. He was managed with prednisone and anti-inflammatory medications with improvement of his rash.
2020Effects of β-Adrenergic Blockade on Metabolic and Inflammatory Responses in a Rat Model of Ischemic Stroke.CellsIschemic stroke provokes an inflammatory response concurrent with both sympathetic nervous system activation and hyperglycemia. Currently, their crosstalk and consequences in stroke outcomes are of clinical attraction. We have provided experimental evidence showing the suppressive effects of the nonselective β-adrenoreceptor antagonist propranolol on hyperglycemia, inflammation, and brain injury in a rat model experiencing cerebral ischemia. Pretreatment with propranolol protected against postischemic brain infarction, edema, and apoptosis. The neuroprotection caused by propranolol was accompanied by a reduction in fasting glucose, fasting insulin, glucose tolerance impairment, plasma C-reactive protein, plasma free fatty acids, plasma corticosterone, brain oxidative stress, and brain inflammation. Pretreatment with insulin alleviated-while glucose augmented-postischemic brain injury and inflammation. Additionally, the impairment of insulin signaling in the gastrocnemius muscles was noted in rats with cerebral ischemia, with propranolol improving the impairment by reducing oxidative stress and tumor necrosis factor-α signaling. The anti-inflammatory effects of propranolol were further demonstrated in isoproterenol-stimulated BV2 and RAW264.7 cells through its ability to decrease cytokine production. Despite their potential benefits, stroke-associated hyperglycemia and inflammation are commonly linked with harmful consequences. Our findings provide new insight into the anti-inflammatory, neuroprotective, and hypoglycemic mechanisms of propranolol in combating neurodegenerative diseases, such as stroke.
2020Anti-inflammatory Activity of Mesenchymal Stem Cells in λ-Carrageenan-Induced Chronic Inflammation in Rats: Reactions of the Blood System, Leukocyte-Monocyte Ratio.InflammationThe variety of chronic diseases caused by a chronic inflammatory process is an unresolved problem in developed countries. Due to this, modern medicine lacks effective, pathogenetic mechanisms of treatment or at least improvement of the quality of life of people with so-called diseases of civilization. The purpose of this study was to investigate the anti-inflammatory and immunomodulatory ability of mesenchymal stem cells (MSCs) in a model of λ-carrageenan secondary chronic inflammation in rats. MSCs derived from rat femoral epiphysis were used. At the current level of medicine, many highly specific markers of chronic inflammation are available that will also be studied later (α-TNF, IL 6, C-reactive protein); however, this article will consider the study of the most accessible but at the same time very informative indicators of the inflammatory process-a common total blood count-leukocytes, leukocyte formula, and LMR. The study was performed on 132 male Wistar rats weighing 180-200 g, which were divided into 12 groups. The inflammation was caused by the introduction of 10 mg λ-carrageenan intramuscular in right hip. After induction of edema, the experimental groups of rats were administered MSCs into the inflamed site, in the amount of 1-2 million cells once. Blood sampling was performed from 6 h to 28 days. With one-way ANOVA followed by Tukey-Kramer multiple comparisons test, p < 0.05, we compared our groups of animals. In the detailed dynamics of inflammation, from the 6th hour to the 28th day (ten terms), the reactions of the blood system and their mechanisms were investigated. There were intact rats-6 animals without any interventions, as well as rats administered MSCs without causing inflammation (6 animals) in experiment. In this experiment, the lymphocyte-monocyte ratio in rats is described for the first time, demonstrating the suppression of chronic inflammation by means of MSCs.
2021ASSOCIATION OF SERUM VASOGENIC AND PROINFLAMMATORY FACTORS WITH CLINICAL RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR DIABETIC MACULAR EDEMA.RetinaTo study the role of serum biomarkers as prognostic factors for qualitative and quantitative response to anti-vascular endothelial growth factor injections for diabetic macular edema (DME).Sixty-seven eyes with DME were treated with intravitreal bevacizumab during a 12-month follow-up period. All cases underwent a baseline workup consisting of 12 inflammatory, metabolic and prothrombotic factors. The following outcomes were evaluated at 3-month intervals until 1 year of follow-up: visual acuity, central subfield thickness (CST), macular volume (MV), % of change from baseline in CST, occurrence of a CST change < 10%, a CST change >20%, and a CST <330 µm, achieving an improvement ≥2 lines of visual acuity, achieving visual acuity ≥20/40.A significant improvement in CST and visual acuity was seen from third month onwards. Twenty-eight (48.1%) cases were classified as "early responders," 24 (35.8%) as "late responders", and 15 (22.4%) as "poor responders." Serum vascular endothelial growth factor-A levels were significantly lower in "poor responders" (P = 0.006). C-reactive protein (hsCRP) was associated with a limited anatomic response (<10% CST change) (P = 0.002, OR = 1.845, cutoff value of hsCRP = 1.84 mg/L). hsCRP was also negatively associated with obtaining a final CST <330 µm (P = 0.04, r2 = 0.112, OR = 0.643). Baseline visual acuity was significantly associated with 12th month visual acuity (P < 0.001, r2 = 0.602) and also with an improvement ≥2 visual acuity lines (P = 0.009, OR = 20.54).Increased high-sensitivity C-reactive protein was associated with limited anatomic response to anti-vascular endothelial growth factor treatment and persistent DME. Poor responders had significantly lower values of serum vascular endothelial growth factor-A, suggesting an alternative pathogenic pathway for persisting DME.
2020Liver cirrhosis in a child associated with Castleman's disease: A case report.World J Clin CasesCastleman's disease (CD) is a lymphoproliferative disorder. TAFRO syndrome is classified as a variant of CD based on its key clinical manifestations of thrombocytopenia, anasarca (generalized edema and pleural effusion), fever (pyrexia), reticulin fibrosis in the bone marrow and the proliferation of megakaryocytes, and organomegaly (such as hepatosplenomegaly and multiple lymphadenopathies); TAFRO syndrome is mainly reported in Japanese patients. To our knowledge, this is the first pediatric case report detailing a CD-associated disorder progressing to cirrhosis.A 10-year old male patient presented with fever and anemia. Six months before hospitalization, he had remarkable abdominal distention. Subsequently, he visited a clinic for a fever that lasted 5 d. The physical findings were marked hepatosplenomegaly and cervical lymphadenopathy. A blood test revealed leukocytosis, microcytic anemia, aspartate aminotransferase-dominant transaminase elevation, high levels of C-reactive protein, polyclonal hypergammaglobulinemia, and high levels of interleukin-6 and vascular endothelial growth factor. Abdominal contrast computed tomography and magnetic resonance imaging suggested cirrhosis, which was confirmed by liver histology. Histological findings in the enlarged hepatic lymph nodes revealed both hyperplasia and atrophy of lymphoid follicles with some vascular hyperplasia and moderate plasmacytosis between the lymphoid follicles, which is compatible with lymph node histology in TAFRO syndrome. Prednisolone was not effective in reducing the patient's symptoms; therefore, the patient was prescribed tocilizumab. To date, the patient remains free of fever and continues to receive tocilizumab.We described the clinicopathological features of TAFRO syndrome to highlight the clinical presentation of this rare disease in a pediatric case.
2020Paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE), improved following surgical resection of prostatic carcinoma: A case report.Urol Case RepRS3PE syndrome is a rare condition that occurs in elderly individuals which can present alone or in association with various rheumatic or malignant diseases. We present a case of a 77-year-old man who was diagnosed with adenocarcinoma of the prostate and initially under active surveillance. 2 months after the diagnosis, he presented with arthralgia in both shoulders and knees, pitting edema of the both hands and feet. The patient underwent radical prostatectomy since the link between prostatic carcinoma and RS3PE was suspected. After 7 months from operation, the patient has no symptoms or signs of RS3PE.
2020Galantamine transdermal patch shows higher tolerability over oral galantamine in rheumatoid arthritis rat model.Drug Dev Ind PharmRheumatoid arthritis (RA) is a chronic autoimmune disease of idiopathic etiology that triggers inflammatory cytokines compromising the joint mobility. Epidemiological evidences recommend the utilization of galantamine (GH) to reverse the anti-inflammatory reactions induced RA. Oral administration of GH is non-selectivity due to its association with serious gastrointestinal symptoms which, could hinder its therapeutic success. Therefore, the present study aimed to validate the therapeutic potential of GH transdermal patches as a novel application to constitute an effective and tolerable delivery system for managing RA in adjuvant arthritis model. RA was induced in Sprague-Dawley rats intradermally by Heat-killed M (0.12 ml/day). Oral GH (1.25 mg/kg/day) and GH transdermal patch (2.5 mg/kg/2 days) were administrated for 14 days, during which the hind paw and body weight (BW) were assessed. Effects of C-reactive protein (CRP), inflammatory cytokines (TNF-α, IL-10 and IL-1β) and Janus kinase (JAK-2) were evaluated. Oral- and transdermal GH significantly improved the hind paw edema in arthritis animal model and offered a protective impact against RA. Oral GH group showed marked decrease in BW than that of transdermal patches group. Transdermal patch group showed a significant decrease in the level of IL-1β more than the oral group. However, no significant difference was detected in the levels of TNF-α and IL-10 between the two groups. It is concluded that GH transdermal patch can be a promising drug delivery system that copes with side effects better than oral GH consequently represents novel strategy in management of RA.
2020Diallyl Disulfide Suppresses Inflammatory and Oxidative Machineries following Carrageenan Injection-Induced Paw Edema in Mice.Mediators InflammDiallyl disulfide (DADS) is the major organosulfur constituent in garlic, with a variety of pharmacological activities including antioxidant and anti-inflammatory. Here, we examined the potential antiedematous impact of DADS- versus carrageenan-mediated paw edema in mice. Carrageenan injection potentiated an inflammatory reaction as presented by the elevated serological C-reactive protein (CRP) levels and transcription of tumor necrosis factor-alpha (TNF-, Tnf), interleukin-1 beta (IL-1, Il1b), interleukin-2 (IL-2, Il2), inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2, Ptgs2), prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1, Ccl1), nuclear factor kappa B (NF-B), and myeloperoxidase (MPO) activity, while interleukin-10 (IL-10) was declined in the injured paw tissue. Additionally, carrageenan elevated lipid peroxidation in terms of malondialdehyde (MDA) and decreased glutathione content (GSH). Remarkably, DADS was found to inhibit the inflammatory signaling, suppressed the developed oxidative damage, and protected the histopathological alterations in the inflamed paw tissue in response to carrageenan injection. Our findings suggest that DADS could be used as an alternative therapy used to alleviate the pathophysiological changes associated with the genesis of paw edema through its potent anti-inflammatory and antioxidant impacts.
2020Hypothesis and Theory: A Pathophysiological Concept of Stroke-Induced Acute Phase Response and Increased Intestinal Permeability Leading to Secondary Brain Damage.Front NeurosciGut integrity impairment leading to increased intestinal permeability (IP) is hypothesized to be a trigger of critically illness. Approximately 15-20% of human ischemic stroke (IS) victims require intensive care, including patients with impaired level of consciousness or a high risk for developing life-threatening cerebral edema. Local and systemic inflammatory reactions are a major component of the IS pathophysiology and can significantly aggravate brain tissue damage. Intracerebral inflammatory processes following IS have been well studied. Until now, less is known about systemic inflammatory responses and IS consequences apart from a frequently observed post-IS immunosuppression. Here, we provide a hypothesis of a crosstalk between systemic acute phase response (APR), IP and potential secondary brain damage during acute and subacute IS stages supported by preliminary experimental data. Alterations of the acute phase proteins (APPs) C-reactive protein and lipopolysaccharide-binding protein and serum level changes of antibodies directed against -cell extract antigen (IgA-, IgM-, and IgG-anti-) were investigated at 1, 2, and 7 days following IS in ten male sheep. We found an increase of both APPs as well as a decrease of all anti- antibodies within 48 h following IS. This may indicate an early systemic APR and increased IP, and underlines the importance of the increasingly recognized gut-brain axis and of intestinal antigen release for systemic immune responses in acute and subacute stroke stages.
2020Organ/space infection is a common cause of high output stoma and outlet obstruction in diverting ileostomy.BMC SurgThe objectives of this study are to identify causes of high-output stoma (HOS) and outlet obstruction (OO), which are major complications of diverting ileostomy.A retrospective analysis was performed in 103 patients who underwent colorectal surgery and diverting ileostomy between December 2015 and November 2018.HOS was found in 32 patients (31.1%) and OO in 19 (18.4%). Organ/space surgical site infection (SSI), anastomotic leakage and OO were significant HOS-related factors in univariate analysis, and OO (odds ratio [OR] 3.39, p = 0.034) was a independent HOS-related factor in multivariate analysis. Organ/space SSI and male were significant OO-related factors in univariate analysis, and organ/space SSI (OR 3.77, p = 0.018) was a independent OO-related factor in multivariate analysis. The white blood cell (WBC) count on postoperative day (POD) 3 was significantly higher in the HOS group compared to the non-HOS group (9765 vs. 8130 /mL, p < 0.05), and the WBC count (9400 vs. 7475 /mL, p < 0.05) and C-reactive protein level (6.01 vs. 2.92 mg/L, p < 0.05) on POD 6 were significantly higher in the OO group compared to the non-OO group.Organ/space infection is involved in the common pathology of HOS and OO. Decreased intestinal absorption due to intestinal edema caused by organ/space SSI and relative stenosis at the abdominal wall-penetrating site are major causes of HOS and OO.
2020Splenial Lesions in Benign Convulsions With Gastroenteritis Associated With Rotavirus Infection.Pediatr NeurolTo investigate clinical risk factors for acute magnetic resonance imaging (MRI) abnormalities in patients with benign convulsions with mild gastroenteritis or benign infantile epilepsy.We investigated clinical and diffusion-weighted imaging findings in 32 patients with benign convulsions with mild gastroenteritis and 22 patients with benign infantile epilepsy who underwent MRI within seven days of seizure onset between 2010 and 2015.Diffusion-weighted imaging showed signal hyperintensity in the splenium of the corpus callosum in seven patients with benign convulsions with mild gastroenteritis, but no abnormalities in patients with benign infantile epilepsy. Patients with benign convulsions with mild gastroenteritis with splenial lesions showed a higher rate of rotavirus detection from feces (P = 0.006), higher serum level of C-reactive protein (P = 0.04), and shorter interval between seizure onset and MRI (P = 0.002) than patients with benign convulsions with mild gastroenteritis without splenial lesions. Multivariate analysis revealed rotavirus infection as a significant risk factor for splenial lesions on diffusion-weighted imaging in patients with benign convulsions with mild gastroenteritis (P = 0.02).Splenial lesions are often seen during acute period in patients with benign convulsions with mild gastroenteritis. Rotavirus infection is a risk factor for splenial lesions in patients with benign convulsions with mild gastroenteritis, suggesting the role of rotavirus to cause edema in the corpus callosum. From our observations, benign convulsions with mild gastroenteritis with a splenial lesion on diffusion-weighted imaging suggests good outcomes, and extensive evaluation of these patients may be unnecessary.
2020Phenolic profile and anti-inflammatory activity of four Moroccan date ( seed varieties.HeliyonDate ( L.) seeds are seen as good drug to cure rheumatoid arthritis and asthma in Moroccan traditional medicine. The present research aimed to study the anti-inflammatory effect, of methanol extract of different date seed varieties using membrane stabilizing effect, nitric oxide radical scavenging activity, inhibition of protein denaturation, carrageenan-induced paw edema and croton oil induced ear edema. The polyphenolic profile was examined using HPLC-DAD. Rutin, quercetin, -coumaric and caffeic acids were the main among the analysed phenolic compounds. Concerning the anti-inflammatory activity, the analysed date seed were significantly effective in scavenging nitric oxide free radical, in stabilisation of erythrocyte membrane and possessed a high anti denaturation effect. In agreement with this finding, date seed exhibited a profound ability to reduce paw and ear swelling induced by carrageenan and croton oil respectively. The biochemical parameters showed that date seed are able to reduce the erythrocyte sedimentation rate (ERS) and C-reactive protein (CRP) concentration in rats used in Carrageenan-induced paw edema model. The predominant phenolic compounds are the potential candidates that drive these activities and the differences observed among varieties are related to their chemical composition. These data suggest that date seeds can be explored as a therapeutic agent for the treatment of inflammatory diseases.
2020Posterior Reversible Encephalopathy Syndrome: Clinical Features and Outcome.Front NeurolPosterior reversible encephalopathy syndrome (PRES) is an acute neurotoxic syndrome that is characterized by a spectrum neurological and radiological feature from various risk factors. Common neurological symptoms includes headache, impairment in level of consciousness, seizures, visual disturbances, and focal neurological deficits. Common triggering factors include blood pressure fluctuations, renal failure, eclampsia, exposure to immunosuppressive or cytotoxic agents and autoimmune disorders. The classic radiographic findings include bilateral subcortical vasogenic edema predominantly affecting the parieto-occipital regions but atypical features include involvement of other regions, cortical involvement, restricted diffusion, hemorrhage, contrast enhancement. This review is aimed to summarize the updated knowledge on the typical and atypical clinical and imaging features, prognostic markers and identify gaps in literature for future research. Systematic literature review using PUBMED search from 1990 to 2019 was performed using terms PRES was performed. While clinical and radiographic reversibility is common, long-standing morbidity and mortality can occur in severe forms. In patients with malignant forms of PRES, aggressive care has markedly reduced mortality and improved functional outcomes. Although seizures were common, epilepsy is rare. Various factors that have been associated with poor outcome include altered sensorium, hypertensive etiology, hyperglycemia, longer time to control the causative factor, elevated C reactive protein, coagulopathy, extensive cerebral edema, and hemorrhage on imaging. Large prospective studies that accurately predict factors that are associated with poor outcomes, determine the pathophysiology, and targeted therapy are required.
2020Chromogranin A provides additional prognostic information in children with severe hand, foot, and mouth disease: A prospective observational study.Int J Infect DisSevere hand, foot, and mouth disease (HFMD) is associated with high mortality in children, and persistent sympathetic activation is a common presentation. The aim of this study was to prospectively investigate serum chromogranin A (CHGA) levels and their prognostic role in this condition.Serum CHGA, creatine kinase myocardial band (CK-MB), serum D-dimer, norepinephrine, blood glucose, lactate, and C-reactive protein levels, white blood cell (WBC) counts, usage of vasopressors, pediatric risk of mortality Ⅲ (PRISM-Ⅲ) scores, and viral etiology were measured upon pediatric intensive care unit (PICU) admission. The correlation between clinical outcomes and the indicators listed above were analyzed, and the ability of CHGA as a biomarker to predict mortality was evaluated.Serum CHGA levels were higher in the non-survivors group than in the survivors group (median (interquartile range): 434.8 (374.3-502.4) vs 183.3 (131.9-246.9) μg/l; p < 0.001) and were correlated with norepinephrine (r = 0.37. p < 0.001), blood glucose (r = 0.32, p = 0.001), lactate (r = 0.25, p = 0.009), WBC (r = 0.20, p = 0.039), and PRISM-Ⅲ scores (r = 0.748, p < 0.0001). Patients suffering neurogenic pulmonary edema, those infected with enterovirus A71, and those requiring more vasopressors had higher serum CHGA levels (median (interquartile range): 385 (239.9-488.8) vs 161 (115.6-222.9), 340.6 (190.6-436.0) vs 150.5 (112.1-210.0), 395.6 (209.1-487.0) vs 167.7 (110.5-240.5) μg/l, respectively; p < 0.0001). The CHGA level upon PICU admission in severe HFMD could be an independent risk factor for mortality (adjusted odds ratio 2.459, 95% confidence interval 1.054-5.906, p = 0.038) with high specificity (87.5%) and sensitivity (82.6%) (cut-off value at 339.6 μg/l).The CHGA level in severe HFMD was found to be associated with cardiopulmonary failure. If measured upon PICU admission, CHGA may provide additional prognostic information in this disease.
2020The occurrence of sacroiliitis in HLA-B*35-positive patients with undifferentiated spondyloarthritis. A cross sectional MRI study.Clin RheumatolTo investigate possible association between sacroiliitis and HLA-B*35 positivity.After excluding patients with axial spondyloarthritis and HLA-B*27 positivity, psoriasis inflammatory bowel disease, preceding infections, or juvenile type of spondyloarthritis, 110 patients were recruited with a diagnosis of undifferentiated axial spondyloarthritis. All of them had inflammatory back pain of short duration (3 months to 2 years) and 72 were HLA-B*35 positive. In order to determine if there is a possible association of sacroiliitis and HLA-B*35 positivity, all patients underwent MRI of sacroiliac joints.A statistically significant association between the detection of bone marrow edema at sacroiliac joints on MRI and HLA-B*35 positivity (χ2 = 6.25; p = 0.022) was found. A logistic regression analysis revealed that the presence of HLA-B*35 allele was associated with a 6 times greater chance of identifying bone marrow edema at sacroiliac joints on MRI (OR 6, 95% CI 1.3-27, p = 0.021). HLA-B*35 positivity was also associated with a 4.7 times greater chance of finding elevated CRP (OR 4.7, 95% CI 1-11.9, p = 0.047) and a 5 times greater chance of finding peripheral joint synovitis (OR 5, 95% CI 1.75-14.3, p = 0.003). HLA-B*35-positive patients had high disease activity (mean ± SD of Bath Ankylosing Spondylitis Disease Activity Index 6.1 ± 1.72 and Ankylosing Spondylitis Disease Activity Score C-reactive protein Index 3 ± 0.64) with a high degree of functional limitations (mean ± SD of Bath Ankylosing Spondylitis Functional Index 5.3 ± 2.16).The data clearly show the association between bone marrow edema on MRI at sacroiliac joints and HLA-B*35 allele in patients with undifferentiated spondyloarthritis. Further work is needed to understand how much this result may influence follow-up of these patients. Key Points • HLA-B*35 allele was associated with a 6 times greater chance of identifying bone marrow edema at sacroiliac joints on MRI in un-axSpa patients. • HLA-B*35 allele was also associated with a 4.7 times greater chance of finding elevated CRP and a 5 times greater chance of finding peripheral joint synovitis in un-axSpa patients. • HLA-B*35 allele could be a potential risk factor for developing sacroiliitis and axSpA.
2020Prognostic factors for VTE and bleeding in hospitalized medical patients: a systematic review and meta-analysis.BloodThere may be many predictors of venous thromboembolism (VTE) and bleeding in hospitalized medical patients, but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify prognostic factors for VTE and bleeding in hospitalized medical patients and searched Medline and EMBASE from inception through May 2018. We considered studies that identified potential prognostic factors for VTE and bleeding in hospitalized adult medical patients. Reviewers extracted data in duplicate and independently and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Of 69 410 citations, we included 17 studies in our analysis: 14 that reported on VTE, and 3 that reported on bleeding. For VTE, moderate-certainty evidence showed a probable association with older age; elevated C-reactive protein (CRP), D-dimer, and fibrinogen levels; tachycardia; thrombocytosis; leukocytosis; fever; leg edema; lower Barthel Index (BI) score; immobility; paresis; previous history of VTE; thrombophilia; malignancy; critical illness; and infections. For bleeding, moderate-certainty evidence showed a probable association with older age, sex, anemia, obesity, low hemoglobin, gastroduodenal ulcers, rehospitalization, critical illness, thrombocytopenia, blood dyscrasias, hepatic disease, renal failure, antithrombotic medication, and presence of a central venous catheter. Elevated CRP, a lower BI, a history of malignancy, and elevated heart rate are not included in most VTE risk assessment models. This study informs risk prediction in the management of hospitalized medical patients for VTE and bleeding; it also informs guidelines for VTE prevention and future research.
2020[Clinical and imaging characteristics of 110 patients with infectious sacroiliitis].Zhonghua Nei Ke Za ZhiTo investigate the clinical and imaging characteristics of infectious sacroiliitis. A total of 110 patients diagnosed with infectious sacroiliitis were retrospectively analyzed between 2008 and 2017.Clinical manifestations and therapeutic responses, laboratory tests such as HLA-B(27), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), T cell spot test for tuberculosis infection(TB-SPOT), Brucella agglutination test ect., blood culture of pathogens, pathological findings as well as magnetic resonance imaging were all recorded and analyzed. Among the 110 patients, the male to female ratio was 44 to 66 with an average age 15-58(29.4±10.8) years and the course of disease 0.3-60 (5.7±13.2) months. As to the pathogens, 71 cases were pyogenic, 24 cases with tuberculous sacroiliitis, and 15 cases were brucellosis infections. The majority of patients (97.3%) had unilateral sacroiliac joint involvement. Ten (9.1%) patients suffered infectious sacroiliac arthritis after delivery. Hip pain was the main clinical manifestation (83/110,75.5%) and fever as the second (77/110,70.0%). HLA-B(27) was positive in 11 patients (10.0%). Both ESR and CRP were elevated in the majority. There were 103 patients receiving sacroiliac joint puncture biopsy. Seven patients were diagnosed through blood culture or brucellosis agglutination test. Bone marrow edema and osteolytic lesions in magnetic resonance imaging (MRI) were more common in pyogenic or tuberculous sacroiliitis than in brucellosis infections. Infectious sacroiliitis should be differentiated from spondyloarthritis, which develops more in female patients, with short disease duration and fever, mostlynegative HLA-B(27). The majority patients present unilateral sacroiliitis. Active inflammatory lesions are usually beyond sacroiliac joints with osteolytic changes in MRI examinations.
2020Acute lung injury after plasma exchange in a patient with anti-MDA5 antibody-positive, rapidly progressive, interstitial lung disease:A case report.Respir Med Case RepThe presence of anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is closely associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis. Despite intensive immunosuppressive therapies, some of these patients still have a poor prognosis with few treatment options. Although removal of pathogenic autoantibodies and cytokines by plasma exchange (PE) could be a treatment option, its safety and efficacy have never been determined. We report a patient with anti-MDA5 Ab-positive RP-ILD who was refractory to intensive therapies including steroids, cyclosporine, and intravenous cyclophosphamide, and then treated by PE to prevent the progression of RP-ILD. Shortly after the initiation of PE therapy, however, his respiratory condition suddenly deteriorated due to acute pulmonary edema and the patient died on the following day. Transfusion-related acute lung injury (TRALI) would be the most likely cause of the acute pulmonary edema because there was no sign of circulatory overload. To the best of our knowledge, this is the first report showing a critical adverse event associated with PE therapy for these patients. This case supports the idea that the presence of ILD could increase a risk for TRALI and therefore we should carefully evaluate the eligibility for PE therapy of anti-MDA5 Ab-positive RP-ILD patients given the risk of acute lung injury. Further studies collecting more clinical data are necessary to assess the efficacy, safety, and risk factors of PE therapy for these patients.
2020Giant pyoderma gangrenosum in a patient with ulcerative colitis: A case report.Medicine (Baltimore)Pyoderma gangrenosum (PG) is a phenomenon of cutaneous ulceration with unknown etiology. About half the cases have associated extracutaneous manifestations or associated systemic diseases. The most commonly associated systemic disorders include inflammatory bowel disease (IBD), hematologic malignancies, autoimmune arthritis, and vasculitis. This is a case report about giant PG with ulcerative colitis (UC), which is extremely rare.A 39-year-old female farmer with UC for the past 3 years presented with multiple painful ulcers, erosion, exudation, and crusting on the right leg for 1 month. A cutaneous examination showed diffusely distributed, multiple, well-defined, deep purulent ulcers on the right medial shank measuring 6 to 20 cm and sporadic worm-eaten ulceration on the right ectocnemial, with severe oozing and erosions. The ulcerations exhibited deep undermined borders, granulated tissue and a black eschar at the base. The right shank and feet were severely swollen, restricting movement. The arteria dorsalis pedis pulse was good, with normal sensation on the skin of the right shank and feet. Laboratory examinations showed a white cell count of 11.8 × 109/L, hemoglobin was 91 g/L, erythrocyte sedimentation rate was 82 mm/h, unelevated procalcitonin, serum C-reactive protein was 131.29 mg/L, and a negative tuberculin skin test. Enteroscopy demonstrated endoscopic evidence of UC. A skin lesion biopsy showed superficial erosion and scarring. Partial epidermal hyperplasia, partial epidermal atrophy and thinning, mild edema of the dermal papill. Most of the middle and lower part of the dermis, showed dense lymphocytes, histiocytes, multinucleated giant cells, and neutrophil infiltration. PG with UC was diagnosed based on clinical manifestations, laboratory examinations and enteroscopy results.She was treated with topical applications of povidone iodine and kangfuxin solution twice daily, methylprednisolone sodium succinate 40 mg and compound glycyrrhizin 60 mg via intravenous drip once a day, along with thalidomide 50 mg twice daily. The UC was controlled with mesalazine.She required multiple therapies to achieve PG healing 3 months later. No PG recurrence was observed during the 1-year follow-up.Recognizing the clinical features of PG and its pathogenic nature, ensuring timely management fundamental for preventing severe destruction and deformity, and control of associated diseases are important aspects of treatment. Combination therapy is essential for PG patients with IBD.
2020Astaxanthin attenuates oxidative stress and inflammatory responses in complete Freund-adjuvant-induced arthritis in rats.Pharmacol RepAstaxanthin (ATX), a natural xanthophyll carotenoid, has shown to exert significant protective effects against various diseases via its antioxidant and anti-inflammatory properties. However, its potential role in arthritis is still not reported. Therefore, the aim of the present study was to investigate the potential anti-arthritic properties of ATX against complete Freund's adjuvant (CFA)-induced arthritis rats.Adjuvant arthritis was induced by single intraplantar injection of complete Freund's adjuvant (CFA) in the left hind paw of adult female Wistar rats. ATX (25, 50 and 100 mg/kg) and indomethacin (5 mg/kg) were given orally from days 14 to 28. The anti-arthritic activity was evaluated through various nociceptive behavioral tests (mechanical allodynia, mechanical hyperalgesia, cold allodynia, and thermal hyperalgesia), paw edema assessment, and arthritis scores. Serum tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and cyclic citrullinated peptide (CCP) antibody levels were assessed. Moreover, malondialdehyde (MDA), nitrite, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels were also evaluated.Oral administration of ATX (50 and 100 mg/kg) exhibited significant anti-arthritic activity via enhancing the nociceptive threshold, reducing paw edema and improving arthritis scores. Moreover, ATX treatment also markedly suppressed inflammatory and oxidative mediators in adjuvant-administered rats.Our findings suggest that ATX possesses potential anti-arthritic activity, which could be attributed to its anti-inflammatory and antioxidant properties.
2019Clinical features of angioedema induced by renin-angiotensin-aldosterone system inhibition: a retrospective analysis of 84 patients.J Community Hosp Intern Med Perspect: Bradykinin-mediated angioedema (AE) induced by antihypertensive drugs primarily affect the head and neck region and may occur even after several years of uneventful treatment. Many facts about the clinical course remain unknown. Diagnosis is not easy, as the clinical appearance resembles allergic AE. No specific diagnostic markers are known and no officially approved treatment is currently available. : All patients who presented to the ORL department between 2010 and 2016 with acute AE were included. Those with a history of renin-angiotensin-aldosterone system (RAAS) blocker intake were defined as RAE and their pathophysiological characteristics and clinical course of the disease were analyzed. : A total of 84 patients (median age of 71 years) with RAE was identified. The majority (80%) was on ACE inhibition. The oral cavity was most often affected. Nearly 60% were medicated for more than 1 year before AE occurred. RAE occurred more often during the morning hours. The necessity for emergency intubation and/or tracheostomy was nine times higher in patients with acute RAE compared to patients with AE due to other reasons. : Event-free, long-term therapy with an RAAS blocker before the first development of edema does not exclude RAE. RAE is associated with an increased risk for emergency airway management. ACE: Angiotensin Converting Enzyme; ACEi AE: ACE inhibitor-induced angioedema; AE: Angioedema; ARB: Angiotensin II receptor 1 blocker; C1 INH: C1 Inhibitor; CI: Confidence Interval; CRP: C-reactive protein; DPP IV: Dipeptidyl peptidase IV; ENT: Ear, Nose and Throat; HAE: Hereditary Angioedema; ICD 10: International Statistical Classification of Diseases and Related Health Problems, 10th Edition; OR: Odds Ratio; ORL: Otorhinolaryngology; RAAS: Renin-Angiotensin-Aldosterone System; RAE: RAAS-blocker-induced angioedema.
2020Morphine consumption during pregnancy exacerbates neonatal hypoxia-ischemia injury in rats.Int J Dev NeurosciHypoxia-Ischemia (HI) is the most common cause of death and disability in human infants. The use of opiate in pregnant women affects their children. The aim of this study was to evaluate the effect of morphine consumption during pregnancy and lactation on vulnerability to neonatal HI in rats.Female Wistar rats were randomly assigned into two groups: Group 1-Rats that did not receive any treatment during pregnancy and lactation and Group 2-Rats that received morphine during pregnancy and lactation. After delivery, male offspring were divided into four groups including: (a) SHAM, (b) SHAM/Morphine (SHAM/MO), (c) HI, (d) HI/Morphine (HI/MO). Seven days after HI induction, neurobehavioral tests were performed, and then, brain tissue was taken from the skull to measure cerebral edema, infarct volume, inflammatory factors, oxidative stress, and brain-derived neurotrophic factor (BDNF).Total antioxidant capacity (TAC) and BDNF levels in the HI/MO group were significantly lower than HI and SHAM groups. TNF-α, C-reactive protein and total oxidant capacity levels in the HI/MO group were significantly higher than HI and SHAM groups. Cerebral edema and infarct volume in the HI/MO group were significantly higher than the HI group.Based on the results, morphine consumption during pregnancy and lactation enhanced the deleterious effects of HI injury in pups.
2020Dry Fasting Physiology: Responses to Hypovolemia and Hypertonicity.Complement Med ResThe aim of this study was to provide a deeper insight into dry fasting (DF) physiology.Ten participants performed DF for 5 consecutive days.The following parameters were monitored daily: cortisol, aldosterone, high-sensitivity C-reactive protein (CRP), erythropoietin, albumin, uric acid, and vitamin C in serum; vasopressin (ADH), adrenocorticotropic hormone (ACTH), renin, angiotensin II, and total antioxidant capacity (TAC) in plasma; hematocrit and erythrocytes in whole blood; osmolality, noradrenaline, dopamine, adrenaline, Na+, and K+ in 24-h urine; waist circumference and body, urine, and stool weight.The following parameters increased: ADH (60 ± 11%), ACTH (176 ± 34%), cortisol (495 ± 75%), urine osmolality (20 ± 4%), CRP (167 ± 77%), renin (315 ± 63%), angiotensin II (74 ± 21%), aldosterone (61 ± 21%), TAC (80.4 ± 17%), uric acid (103 ± 19%), albumin (18.4 ± 2.4%), erythrocytes (13.4 ± 2.2%), hematocrit (11 ± 1.8%), and the excretion of noradrenaline (40.3 ± 10%) and dopamine (17 ± 5%). The following parameters decreased: waist circumference (8.20 ± 0.61 cm), body weight (7.010 ± 0.3 kg), erythropoietin (65 ± 18%), and the excretion of adrenaline (38 ± 4%) and Na+ (60 ± 16%). The excretion of K+ remained unchanged. Vitamin C decreased, showing a half-life of 4.8 ± 0.7 days. The percent ratios of lost weight components were: urine (52.2 ± 3.7%), insensible water loss (32.2 ± 1.4%), stool (5 ± 0.3%), and respiratory gases, i.e., expired CO2 - incorporated O2 (10.6 ± 5.4%).The mechanisms underlying the hypertonicity and hypovolemia compensation and the ratio analysis of lost weight components were presented. DF demonstrated short-term antioxidant, anti-ischemic, immune-stimulating, anti-edematous, and anti-inflammatory effects. The results may have an impact on developing new concepts for the treatment of edema, obesity, and inflammatory and ischemic diseases.
2020Active inflammatory changes around the pubic symphysis in patients with axial spondyloarthritis: Magnetic resonance imaging characteristics and association with clinical factors.Eur J RadiolTo determine the prevalence of active inflammatory changes around the pubic symphysis on MRI scans in patients with axial spondyloarthritis, and to evaluate its association with clinical factors.A retrospective analysis of MRI scans of 128 patients clinically diagnosed with axial spondyloarthritis was performed to assess the presence of active inflammatory changes around the pubic symphysis (bone marrow edema/osteitis and enthesitis). The clinical factors of the patients with and without active inflammatory changes around the pubic symphysis were compared.MRI scans showed active inflammatory changes around the pubic symphysis in 23 patients (18.0 %); 9 patients showed bone marrow edema/osteitis in the parasymphyseal pubic bone without soft tissue changes, 9 patients showed enthesitis with bone marrow edema/osteitis, and 5 patients showed enthesitis without bone marrow edema/osteitis. The median age of patients with active symphysis pubis changes was higher than that of those without active symphysis pubis changes (p < 0.001). C-reactive protein level and erythrocyte sedimentation rate in the active symphysis pubis group were both higher than those of the non-active symphysis pubis group (p = 0.001 and <0.001, respectively).Active inflammatory changes around the pubic symphysis were seen in 18.0 % of the patients diagnosed with axial spondyloarthritis undergoing pelvic MRI, and were associated with older age and elevated acute phase proteins.
2021Systemic inflammation status at admission affects the outcome of intracerebral hemorrhage by increasing perihematomal edema but not the hematoma growth.Acta Neurol BelgAcute stress and inflammation responses are associated with worse outcomes in intracerebral hemorrhage (ICH) but the precise mechanisms involved are unclear. We evaluated the effect of neutrophil-to-lymphocyte ratio (NLR) in ICH outcome, with focus on hematoma expansion and early cerebral edema. In a retrospective study, we included all patients with primary ICH admitted to our center within 24-h from symptom onset from January 2014 to February 2015. We retrieved demographic and medical history data, Glasgow Coma Scale scores, blood cell counts, glucose, and C-reactive protein, and calculated NLR. We obtained hematoma volumes by computerized planimetry. Outcomes included independence at 90 days (modified Rankin scale 0-2), mortality at 30 days, significant hematoma expansion (> 33% or > 6 mL) and early cerebral edema causing significant midline shift (> 2.5 mm) at 24 h. We included 135 patients. NLR independently associated with independence at 90 days (adjusted odds ratio (aOR) 0.79, 95% CI 0.67-0.93, p = 0.006) significant cerebral edema (aOR 1.08, 95%CI 1.01-1.15, p = 0.016) but not hematoma expansion (aOR 0.99, 95%CI 0.94-1.04, p = 0.736). The severity of midline shift was positively correlated with NLR (adjusted beta = 0.08, 95% CI 0.05-0.11, p < 0.001). In ICH, an immediate and intense systemic inflammatory response reduces the likelihood of a better functional outcome at 90 days, which is more likely to be explained by perihematomal edema growth than due to a significant hematoma expansion. These findings could have implications in new treatment strategies and trial designs, which endpoints tend to target exclusively hematoma enlargement.
2020[Clinical features of pulmonary thromboembolism of eight children].Zhonghua Er Ke Za ZhiTo improve the diagnosis and therapy of childhood pulmonary thromboembolism (PTE) by analyzing the clinical features of this rare condition. A total of 8 pediatric patients (4 males, 4 females) with PTE diagnosed in the Children's Hospital of Zhejiang University School of Medicine from March, 2014 to March, 2019 were enrolled. The clinical manifestation, laboratory results, imaging findings, diagnosis and treatment were summarized. Among these 8 cases, aged from 9 hours to 14 years and 10 months. Fever was found in 4 cases, cough aggravation in 4, short of breath in 3, chest pain in 2, abdominal and back pain in one, hemoptysis in 2, cyanosis in 1, and edema of lower extremities in 2. Physical examination found decreased breath sound in 2 cases, phlegm rale in 3, and pleural friction rub in one. Pleural effusion was found in 5 cases by ultrasound. Plasma D-dimer increased in 6 cases (0.66-9.96 mg/L) and hypersensitive C-reactive protein elevated in 5 cases (10.78-78.00 mg/L). Chest enhanced CT showed pulmonary artery or venous filling defects, including pulmonary artery embolism in 7 cases and pulmonary vein embolism in one. The primary disease of these patients included pneumonia in 4 cases, nephritis in 2 and postoperative congenital heart disease in 2. Apart from one case who withdrew the treatment and was discharged, the other 7 patients received anticoagulant treatment had good outcome. For children with pneumonia, immune disorders, long-term hormone therapy, cardiovascular invasive operation or other high-risk factors, PTE should be considered when fever, cough aggravation, short of breath, chest and back pain with pleural effusion are present. Chest enhanced CT scan should be performed as soon as possible, and anticoagulation should be started once the diagnosis is confirmed.
2019[Association of YKL-40 in bronchoalveolar lavage fluid with airway damage in children with Mycoplasma pneumoniae pneumonia].Zhongguo Dang Dai Er Ke Za ZhiTo investigate the association of YKL-40 in bronchoalveolar lavage fluid (BALF) with airway damage in children with Mycoplasma pneumoniae pneumonia (MPP).A total of 60 children with MPP who were admitted to the hospital were enrolled as the MPP group, and 12 children with bronchial foreign bodies were enrolled as the control group. According to the imaging findings, the MPP group was further divided into 3 subgroups: pulmonary patchy shadow (n=34), pulmonary consolidation (n=19) and pulmonary ground-glass opacity (n=7). According to the bronchoscopic findings, the MPP group was further divided into 3 subgroups: mucosal congestion/edema (n=38), mucous secretion (n=18) and plastic bronchitis (n=4). The clinical manifestations and laboratory characteristics of the children with MPP were analyzed, the expression of YKL-40 in BALF was measured.The MPP group had significantly higher levels of serum lactate dehydrogenase and BALF YKL-40 than the control group (P<0.05). The pulmonary consolidation subgroup had significantly higher levels of serum C-reactive protein and lactate dehydrogenase than the pulmonary patchy shadow subgroup (P<0.05), and the pulmonary consolidation and pulmonary ground-glass opacity subgroups had a significantly higher level of BALF YKL-40 than the pulmonary patchy shadow subgroup (P<0.05). The plastic bronchitis subgroup had a significantly higher level of BALF YKL-40 than the mucous secretion and mucosal congestion/edema subgroups (P<0.05). The mucous secretion and plastic bronchitis subgroups had a significantly higher proportion of children with shortness of breath than the mucosal congestion/edema subgroup (P<0.05). The plastic bronchitis subgroup had significantly higher serum levels of C-reactive protein and lactate dehydrogenase than the mucosal congestion/edema subgroup (P<0.05).The level of BALF YKL-40 is associated with airway damage and disease severity in children with MPP.
2019[Adrenal hemorrhage in a patient with systemic lupus erythematosus].Beijing Da Xue Xue Bao Yi Xue BanA 58-year-old female was referred to our department with intermittent suffocation for 1.5 years, aggravated for a month. 1.5 years before she developed oral ulcer, raynaud phenomenon, proteinuria, bilateral pleural effusion, ANA and anti-dsDNA positive. This patient was diagnosed with systemic lupus erythematosus (SLE). After given hormones, hydroxychloroquine sulfate (HCQ), her symptom relieved soon. The patient stopped her pills 1 year ago. One month ago, she had chest tightness, increased urine foam, and suffered from oliguria. Her admission medical examination: blood pressure (BP) 130/80 mmHg, conjunctiva pale, and lower lung breath sounds reduced. There was no tenderness, rebound pain and abdominal muscle tension in the abdomen. Liver and spleen rib inferior, mobile dullness negative, and lower extremity edema. Blood routine tests were performed with hemoglobin (HGB) 57 g/L. Urine routine: BLD (3+). 24-hour urinary protein 3.2 g. serum albumin 20.5 g/L, C-reactive protein (CRP) 12.85 mg/L, erythrocyte sedimentation rate (ESR) 140 mm/h. Antinuclear antibody (ANA) (H)1:10 000, anti-dsDNA antibody 1:3 200; anti-Smith antibody, anti-U1-snRNP/Sm antibody were positive, blood complement 3(C3) 0.43 g/L, complement 4(C4) 0.07 g /L. Anticardiolipin antibody (ACL), anti-β2-GP1, lupus anticoagulant (LA) were negative; HRCT suggested bilateral medial pleural cavity product liquid. Admission diagnosis: SLE lupus nephritis, anemia, pleural effusion, and hypoproteinemia. We treated her with methylprednisolone 1 000 mg×3 d, late to 48 mg/d and cyclophosphamide 1.0 g, HCQ 0.2 g bid, gamma globulin 10 g×5 d. Day 2 of treatment, this patient developed acute right upper quadrant pain, not accompanied by nausea, vomiting, blood stool and diarrhea. Antipyretic antispasmodic treatment was invalid, after the morning to ease their own abdominal pain. Day 4 of treatment, daytime blood HGB 77 g/L. Bilateral renal vascular ultrasound: bilateral renal artery blood flow velocity was reduced. The abdominal pain of the above symptoms recurred at night, BP was 120/80 mmHg, and no positive signs were found on abdominal examination. No abnormality was found in the vertical abdominal plain film. Blood routine examination: HGB 53 g/L, Plasma D dimer 2 515 μg/L, amylase in hematuria was normal, the stool occult blood was negative. Abdominal computed tomography (CT): normal structure of right adrenal gland disappeared, irregular mass shadow could be seen in adrenal region, CT value was about 50 HU. Morphological density of left adrenal gland was not abnormal. The retroperitoneum descended along the inferior vena cava to the right iliac blood vessel and showed a bolus shadow. The density of some segments increased. The lesion involved the right renal periphery and reached the left side of abdominal aorta. Most lesions surrounded the inferior vena cava, the right renal vein and part of the small intestine. The boundary between the upper lesion and the vena cava was unclear. Iodinecontaining contrast agent was taken orally. No sign of contrast agent overflowing was found in the abdominal cavity. Hematoma and exudative changes were considered in retroperitoneum. CONCLUSION of contrast-enhanced ultrasound of blood vessels: The retroperitoneal inferior vena cava (volume 3.5 cm×3.5 cm×1.5 cm) was hypoechoic and had no blood flow lesion. The adrenal gland had a high possibility of origin. Left renal vein thrombosis extended to inferior vena cava. According to the above data, it was analyzed that the cause of retroperitoneal hematoma of the patient was left adrenal vein thrombosis caused by hypercoagulable state, which led to vascular rupture and hemorrhage caused by increased vascular pressure in adrenal gland. Therefore, on the basis of continuing to actively treat the primary disease, and on the basis of dynamic observation of no active hemorrhage for 3 days, the anticoagulant therapy was continued with 10 mg/d of apixaban. Clinical symptoms were gradually eased, HGB did not decrease. Two weeks later, the ultrasonic examination showed that the irregular cluster hypoechoic range behind the inferior vena cava was significantly smaller than that before (1.8 cm×1.2 cm×0.7 cm). Abdominal CT examination after 1 month showed that there was no abnormal morphological density of bilateral adrenal glands and basic absorption of retroperitoneal exudation. Adrenal hemorrhage is uncommon. SLE with adrenal hemorrhage is rarer. In SLE patients, especially those complicated with APS, if abdominal pain accompanied by HGB decrease occurs, except after gastrointestinal hemorrhage, the possibility of adrenal hemorrhage should be warned.
2019High-Sensitivity C-Reactive Protein and Acute Kidney Injury in Patients with Acute Myocardial Infarction: A Prospective Observational Study.J Clin MedAccumulating evidence suggests that inflammation plays a key role in acute kidney injury (AKI) pathogenesis. We explored the relationship between high-sensitivity C-reactive protein (hs-CRP) and AKI in acute myocardial infarction (AMI). We prospectively included 2,063 AMI patients in whom hs-CRP was measured at admission. AKI incidence and a clinical composite of in-hospital death, cardiogenic shock, and acute pulmonary edema were the study endpoints. . Two-hundred-thirty-four (11%) patients developed AKI. hs-CRP levels were higher in AKI patients (45 ± 87 vs. 16 ± 41 mg/L; < 0.0001). The incidence and severity of AKI, as well as the rate of the composite endpoint, increased in parallel with hs-CRP quartiles ( for trend <0.0001 for all comparisons). A significant correlation was found between hs-CRP and the maximal increase of serum creatinine (R = 0.23; < 0.0001). The AUC of hs-CRP for AKI prediction was 0.69 ( < 0.001). At reclassification analysis, addition of hs-CRP allowed to properly reclassify 14% of patients when added to creatinine and 8% of patients when added to a clinical model. In AMI, admission hs-CRP is closely associated with AKI development and severity, and with in-hospital outcomes. Future research should focus on whether prophylactic renal strategies in patients with high hs-CRP might prevent AKI and improve outcome.
2019Expert Group Consensus Opinion: Role of Anti-inflammatory Agents in the Management of Type-2 Diabetes (T2D).J Assoc Physicians IndiaDiabetes is a major public health emergency of the 21st century. Results of the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study have found prevalence of diabetes and prediabetes in India to be as high as 7.3% and 10.3%, respectively with nation-wide projection of 77.2 million people with prediabetes and 69.2 million with diabetes. It is well established that insulin resistance (IR) and islet β-cell failure are the two major features of T2D Multiple mechanisms including glucotoxicity, lipotoxicity, oxidative stress, endoplasmic reticulum stress, formation of amyloid deposits in the islets, etc. have been hypothesized to participate in the pathology of the disease. In the concluding decade of the last century, numerous studies - prospective and cross-sectional, have confirmed the role of chronic low-grade inflammation as a pathogenetic factor of T2D. It has been shown that increased levels of various inflammatory markers and mediators including fundamental markers like white blood cell count, C-reactive protein (CRP) to the more specific circulating cytokines like, interleukin-6 (IL-6), IL-1β, plasminogen activator inhibitor-1 (PAI-1), etc. correlate with incident T2D. Based on the robust evidence implying the role of inflammation in T2D pathogenesis, several studies have proven that the proinflammatory cytokines play a central role in the development of microvascular diabetic complications such as nephropathy, retinopathy, and neuropathy. Inflammation in T2D causes accelerated atherosclerosis which predisposes to CVD, the leading cause of mortality in these patients. Recently there is a considerable increase in the interest among the researchers about anti-inflammatory therapies in the setting of chronic disorders such as T2D and CV diseases. In a multi-country study conducted in Asia, approximately 50% of Indian respondents had poor diabetes control. Most patients initially respond to sulfonylurea and/or metformin, and later these agents lose their effectiveness with time. Therapeutic option in patients uncontrolled on two-drug combination therapy is either to add third oral drug or insulin. However, use of insulin is limited due to its high cost and poor compliance. Majority of new treatment options like GLP1 agonists, insulin analogs and SGLT2 inhibitors are costly considering they are still under patent. The thiazolidinedione class of drugs is associated with adverse effects like fluid retention and weight gain that may result in or exacerbate edema and congestive heart failure. Thus there is a need for a safe and inexpensive treatment option for the management of uncontrolled T2D. Considering the role of inflammation in T2D pathogenesis, the drug should not only have antihyperglycemic effects but also reduce inflammatory burden thus reducing the progression and complications of T2D. The current interest is apparently directed towards drugs targeting inflammation acting at different stages of the inflammatory cascade. In the recently published CANTOS study, canakinumab, a selective, high-affinity, fully human monoclonal antibody which inhibits IL-1β, has no consistent long-term benefits on HbA1c. Other selective inhibitors like anakinra (IL-1 receptor antagonist) and etanercept (TNF inhibitor) too have yielded modest effects on glycemic parameters and insulin sensitivity. However, hydroxychloroquine (HCQ), a broad anti-inflammatory agent has been shown to reduce HbA1c by 0.87%. Hydroxychloroquine (HCQ) is considered as one of the safest disease modifying anti-rheumatic drug, used widely for the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The effect of HCQ in preventing development of diabetes in patients with chronic inflammatory diseases was highlighted in a prospective observational study of 4905 adults with rheumatoid arthritis and no diabetes with 21.5 years of follow-up. Patients who took HCQ for more than 4 years had a significant 77% lower risk of diabetes compared with non users of HCQ (RR, 0.23; 95% CI, 0.11-0.50). Taking cue from this study highlighting the anti-diabetic effect of HCQ, pioneering research studies evaluating these effects of HCQ were conducted in India. In 2014, hydroxychloroquine 400 mg got DCGI approval as an adjunct to diet and exercise to improve glycemic control of patients on metformin, sulfonylurea combination in Type 2 diabetes.
2019A Novel Inextensible Endoscopic Tube Versus Traditional Extensible Retractor System in Single-Level Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Prospective Observation Study.Pain PhysicianCurrently, various retractor systems are widely used for access to the lumbar spine in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). Nevertheless, studies concerning the comparison of extensible retractor and inextensible tube systems are quite rare.This article was to compare perioperative characteristics, clinical outcomes, and multifidus muscle injury of obconic inextensible tube versus extensible retractor system for single-level MIS-TLIF.A prospective observational study on 91 patients with a mean follow-up of 20.0 ± 4.1 months.This study was conducted by a university-affiliated hospital in a major Chinese city.From April 2015 to May 2016, 91 consecutive patients who underwent MIS-TLIF procedure using an obconic inextensible endoscopic tube or extensible retractor system were enrolled in this study. Operation parameters such as incision length, blood loss, postoperative drainage volume, surgical time, analgesic use rate, time to ambulation, and postoperative hospitalization days were evaluated. The concentration of white blood cells, interleukin-6, interleukin-8, tumor necrosis factor alpha, and creatine phosphokinase (CPK)-MM of the enrolled patients were measured for postoperative traumatic stress and muscle injury. Multifidus muscle edema and atrophy were evaluated by T2-weighted magnetic resonance imaging (MRI) at 3 different time points (preoperative, postoperative, and 1-year follow-up). Clinical outcomes such as Visual Analog Scale (VAS) score, Japanese Orthopedic Association (JOA) score, Oswestry Disability Index (ODI) score, fusion rates, and MacNab criteria were assessed for patients' symptoms.In terms of baseline characteristics, the 2 groups were similar regarding sample size, gender, age, symptoms duration, operation level, body mass index, physical examination, and all the clinical outcomes measures (P > 0.05). Perioperative analysis showed that the inextensible group had comparative incision length, blood loss, operation time, time to ambulation, and postoperative hospitalization (P > 0.05). The inextensible tubular group had less postoperative drainage volume and analgesic use rate (P < 0.05). The concentration level of CPK-MM and c-reactive protein (CRP) was lower in the inextensible tubular group compared with the extensible retractor group.No significant difference was found between the 2 groups regarding MRI T2 signal intensity ratio of multifidus muscle at the immediate postoperative period. The MRI T2 signal intensity ratio of multifidus muscle was lower in the inextensible tubular group than the extensible retractor group at the 1-year follow-up period. The VAS scores for low back pain and leg pain improved significantly in both groups after surgery, as did the JOA and ODI scores. However, there were no significant differences between the 2 groups regarding the preoperative and final follow-up VAS, JOA, and ODI scores, fusion rates, and the distribution of the MacNab criteria.This was not a randomized controlled trail, which could provide more evidence-based medicine conclusions.The obconic inextensible endoscopic tube system via the transforaminal approach for lumbar interbody fusion is a safe and sufficient technique. When compared with the extensible retractor system, it has comparable clinical outcomes, with additional significant benefits of less postoperative drainage volume and analgesic use rate, less multifidus muscle injury in terms of lower CPK-MM levels at immediate postoperative period, less change in CRP, and less change in MRI T2 signal intensity ratio of multifidus muscles at 1-year follow-up.Minimally invasive, endoscopic, lumbar interbody fusion, tubular, multifidus muscle.
2019Trametes orientalis polysaccharide alleviates PM-induced lung injury in mice through its antioxidant and anti-inflammatory activities.Food FunctThis paper examined the molecular conformation of Trametes orientalis polysaccharide (TOP-2) and evaluated the ameliorative effects of TOP-2 on PM2.5-induced lung injury in mice. The Congo red test and transmission electron microscopy (TEM) showed that TOP-2 had a triple-helical structure. PM2.5-induced pulmonary edema was ameliorated by TOP-2 intervention. PM2.5 notably increased the number of inflammatory cells and percentages of neutrophils in bronchoalveolar lavage fluid (BALF), and notably reduced the percentages of macrophages in BALF, while TOP-2 abolished these effects. The increased levels of total protein, albumin, C-reactive protein (CRP), myeloperoxidase (MPO), lactate dehydrogenase (LDH), alkaline phosphatase (AKP), acid sphingomyelinase (ASM), TNF-α, IL-1β and IL-6 in BALF after PM2.5 exposure were inhibited by TOP-2. In addition, TOP-2 could not only remarkably promote the activities of antioxidant enzymes, but also reduce the levels of malondialdehyde (MDA), protein carbonyl group (PCG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Furthermore, TOP-2 up-regulated the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) and inhibited the activation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome in the lung tissue. These results hint that TOP-2 could alleviate PM2.5-induced lung injury in mice via its antioxidant and anti-inflammatory activities, and the underlying mechanisms, at least partly, depended on activation of the Nrf2/HO-1 pathway and inhibition of NLRP3 inflammasome.
2019[Orbital cellulitis in children: Report of 60 cases].J Fr OphtalmolThe goal of this study was to describe the epidemiological, etiological, clinical and therapeutic features and clinical course of orbital cellulitis in children, and to assess the risk factors for retroseptal involvement.This was a retrospective study including 60 children (67 eyes) diagnosed with orbital cellulitis. Two groups were defined according to the clinical form: pre- or retroseptal.We studied 29 cases (34 eyes) of preseptal cellulitis and 31 cases (33 eyes) of retroseptal cellulitis. The mean age was 4 years. The male: female ratio was 1.3. The prescription of anti-inflammatory drugs and antibiotics prior to hospitalization was noted in respectively four and 10 patients. Eyelid edema was the principal sign (100% of cases); exophthalmia was noted in 19 eyes, ptosis in 27 eyes and chemosis in 10 eyes. Oculomotor disorders were present in 4 eyes. The mean C-reactive protein level was 53.15±27mg/l in preseptal cellulitis and 92.09±21mg/l in the retro-septal cases. Orbital computed tomography was performed in 31 patients and MRI in 5 patients. The pathway of entry of the orbital infection was primarily from the sinuses (23 cases). All of our patients had received broad spectrum intravenous antibiotic therapy. Three children had a cavernous sinus thrombosis and had been treated with anticoagulant therapy. Surgical drainage was performed in five patients. The course was favorable and without sequelae for all the patients. Two independent risk factors for retroseptal involvement were identified: the prescription of anti-inflammatory drugs prior to hospitalization, and sinus involvement.Orbital cellulitis in children is a serious infection and requires close collaboration between the ophthalmologist, otolaryngologist, and pediatrician in order to be diagnosed and treated early so as to improve the prognosis for vision and life.
2019Anti-Inflammatory and Anti-Hyperuricemic Functions of Two Synthetic Hybrid Drugs with Dual Biological Active Sites.Int J Mol SciThe present study aimed to test the anti-inflammatory and xanthine oxidase inhibitory activities of two synthesized molecules and compare them to routinely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac and the serum urate-lowering drug, allopurinol. The anti-inflammatory effects of the designed compounds (A and B) were evaluated in carrageenan (CAR)-induced paw edema in mice. The levels of nitric oxide and myeloperoxidase activity were measured in paw skin using biochemical methods. Additionally, prostaglandin E2 (PGE2), C-reactive protein (CRP), cyclooxygenase-2 (Cox-2), tumor necrosis factor-α (TNFα), interleukin (IL)-1β, IL-2 and IL-10, and monocyte chemoattractant protein-1 (MCP1) were assessed by enzyme-linked immunosorbent assay (ELISA). The expression of inflammation-related genes was confirmed by real-time qPCR. The expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) were estimated using immunohistochemistry, and xanthine oxidase inhibitory activity was evaluated using an in vitro assay. The results revealed that compounds A and B decreased inflammation, as was observed by a reduction in the elevation of all the tested markers. In addition, the tested compounds markedly decreased paw swelling, mobilization of inflammatory cells, iNOS-, and NF-κB-immunoreactive cells in a mouse model of paw edema. Interestingly, both compounds were potent xanthine oxidase inhibitors as well as Cox inhibitors with higher activity in favor of compound B providing potential dual acting series of anti-hyperuricemic and anti-inflammatory therapeutic agents.
2019Osteomyelitis of the pubic symphysis caused by methicillin-resistant Staphylococcus aureus after vaginal delivery: a case report and literature review.BMC Infect DisOsteomyelitis of the pubic symphysis is a rare cause of pelvic pain after delivery, mainly caused by Staphylococcus aureus and Pseudomonas aeruginosa. The clinical context is the same as the more common diastasis of the pubic bone, but the presence of intense local pain in association with fever should prompt further clinical work-up based on blood chemistry, microbiology and diagnostic imaging. We report the first case of methicillin-resistant Staphylococcus aureus osteomyelitis of the pubic symphysis occuring after the delivery.A 39-year-old woman developed pain over the pubic bone 12 h after the delivery. After 72 h fever rose and laboratory examination showed elevation of C-reactive protein and procalcitonin levels. Pelvic x-rays and magnetic resonance showed pubic diastasis, joint effusion, tiny irregularities of articular surfaces and, severe bone edema. The patient was started on broad spectrum intravenous (IV) antibiotics (piperacillin-tazobactam) and then replaced to IV vancomycin and oral levofloxacin based on antibiogram result. She was then discharged with oral antibiotic therapy and fully recovered.Due to the rarity of this disease, we compared our experience with the other cases of osteomyelitis of pubic symphysis occurring in peri-postpartum reported in the literature. The course of osteomyelitis was favourable in all patients, and only in one case an additional orthopedic procedure for symphysis fixation was necessary. Knowledge of this rare condition is important to enable prompt diagnosis and treatment.
2020Clinical features and phylogenetic analysis of severe hand-foot-and-mouth disease caused by Coxsackievirus A6.Infect Genet EvolCoxsackievirus A6 (CA6) infection may lead to high hand-foot-and-mouth disease (HFMD) aggregation in children. We aimed to analyze the clinical and phylogenetic features of severe CA6-associated pediatric HFMD.The clinical and laboratory features of 206 and 55 children with mild and severe CA6-associated HFMD, respectively, were summarized. The CA6 phylogenetic tree was depicted using combinatorial analysis of the VP1-encoding regions and neighbor-joining method.CA6 was the major pathogen both in mild and severe HFMD in 2017. Most CA6-associated severe HFMD cases showed high fever, skin rash, age younger than 36 months, and elevated white blood cell and C-reactive protein levels, and there were no significant differences compared to the mild cases (p > 0.05). The severe cases were significantly more likely (p < 0.05) to show male sex, long fever duration, decreased oral intake, tonsil enlargement, diarrhea, vomiting, elevated levels of creatine kinase and blood glucose, and positive fecal occult-blood test results. Severe complications included aseptic meningitis (29/55, 52.7%) and pulmonary edema (6/55, 10.9%) were observed in severe cases. Furthermore, genetic analyses showed all CA6 isolates belonged to lineage E2, and two amino acid changes of V174I and T283A in VP1 may be associated with the severity of HFMD.CA6 has become a major cause of HFMD with severe systemic disorders. V174I and T283A of VP1 may be associated with the severity of CA6 infection. These findings could raise awareness of the clinical importance of CA6 infection among practitioners.
2020Favorable outcome of extended curettage for the treatment of unifocal chronic sclerosing osteomyelitis of clavicle: a case series.J Shoulder Elbow SurgChronic sclerosing osteomyelitis (CSO) of the clavicle, especially its unifocal subset, is scarcely reported, and little is known about its characteristic features and treatment. We aim to describe the characteristic features and outcome of treatment in a series of patients with unifocal CSO of the clavicle.In a retrospective study, we identified 6 patients with a diagnosis of unifocal CSO of the clavicle. All patients underwent a core needle biopsy, and histologic examination confirmed the diagnosis. Laboratory investigations included the white blood cell count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and bacteriologic culture. We used plain radiographs, computed tomography scanning, and magnetic resonance imaging for the radiologic evaluation.The median age of the patients was 16.5 years (range, 10-29 years). The ESR and CRP level were elevated in 5 cases. The bacterial culture results were negative in all cases. Sclerosis was the main radiologic symptom. Other radiologic features such as bone expansion, cystic change, periosteal reaction, cortex destruction, and soft-tissue edema could accompany sclerosis. Anti-inflammatory medications temporarily and slightly reduced the symptoms. Four patients underwent extended curettage, in whom the clinical, radiologic, and laboratory symptoms considerably subsided. In the 2 patients who did not agree to undergo surgical intervention, the clinical and radiologic symptoms fluctuated at the follow-up visits.Unifocal CSO of the clavicle is associated with negative bacterial culture results, but the ESR and CRP level are frequently elevated. The symptoms fluctuate if not adequately treated. Extended curettage could be regarded as the treatment of choice.
2019Antinociceptive and anti-inflammatory effects of N-acetylcysteine and verapamil in Wistar rats.Korean J PainAntinociceptive anti-inflammatory drugs have many adverse effects. The goal of this investigation is to study the probable anti-inflammatory and analgesic effects of verapamil and N-acetylcysteine (NAC) in experimental rats.Adult male Wistar rats were randomly divided into 4 groups in the antinociceptive study, each containing 6 rats; the normal control group, which received saline (1 mL/kg); the diclofenac group, which received diclofenac sodium (5 mg/kg); the NAC group, which received NAC (125 mg/kg); and the verapamil group, which received verapamil (8 mg/kg). In the anti-inflammatory study, 5 groups were used, the 4 previous groups with the addition of an edema control group, received saline and were subjected to formalin test. Hot plate latency time was recorded for antinociceptive evaluation. Paw edema thickness and biochemical parameters were recorded for anti-inflammatory evaluation.Administration of NAC showed significant prolongation of hot plate latency time at 1 hour when compared to the control group while verapamil showed a significant prolongation of hot plate latency time at 1 and 2 hours when compared to the control group and NAC group values. Administration of NAC and verapamil significantly decreased paw edema thickness at 2, 4, and 8 hours when compared to edema control values. Regarding biochemical markers, NAC and verapamil significantly decreased serum nitric oxide synthase, C-reactive protein, and cyclooxygenase- 2 levels compared to the edema control value. In accordance, a marked improvement of histopathological findings was observed with both drugs.NAC and verapamil have antinociceptive and anti-inflammatory effects comparable to diclofenac sodium.
2020Anti-arthritic activity of ferulic acid in complete Freund's adjuvant (CFA)-induced arthritis in rats: JAK2 inhibition.InflammopharmacologyFerulic acid (FA), a hydroxycinnamic acid, is an organic compound found in several plant species. Previous studies have shown that FA contains anti-inflammatory and anti-arthritic properties. This study aimed to investigate the anti-arthritic activity and possible mechanism(s) of action of FA in complete Freund's adjuvant (CFA)-induced arthritis. The progression of rheumatoid arthritis (RA) involves the activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway by proinflammatory cytokines. Molecular docking of FA showed promising Janus kinase 2 (JAK2) inhibition with a docking score of - 6.7, which is comparable with that of ruxolitinib, a standard inhibitor. However, in vitro JAK2 inhibition assay showed a half maximal inhibitory concentration (IC50) of 6.67 ± 0.88 µg/ml. Both doses of FA (25 and 50 mg/kg) significantly attenuated primary (volume of paw edema) and secondary lesions. CFA-induced arthritic rats showed a significant decrease in body weight, A/G ratio, and Hb but showed a greater arthritic index, ESR levels, and percentage of lymphocytes. These alterations were significantly reduced in rats treated with FA and prednisolone. FA also reversed changes to biochemical parameters and inflammatory markers, such as C-reactive protein (CRP) and rhematoid factor (RF). Additionally, we found CFA-induced arthritis triggered the secretion of TNF- α, increased JAK2 levels, and reduced TGF-β levels in tissue homogenates. However, in rats treated with FA, such alterations significantly improved. Thus, our results reveal that FA contains anti-arthritic activity, which is possibly mediated by the inhibition of the JAK/STAT pathway.
2020Malnutrition Predisposes to Endotoxin-Induced Edema and Impaired Inflammatory Response in Parenterally Fed Piglets.JPEN J Parenter Enteral NutrPoor nutrition status is common among hospitalized children and children in low-income countries and may be associated with increased susceptibility to edema and infections. We hypothesized that poor nutrition status, established with a suboptimal composition of parenteral nutrition (PN), predisposes to endotoxemia-induced edema, oxidative stress, and dysregulated immune responses.Using a 2 × 2 factorial design, 3-day-old piglets (n = 40) were given either optimal or suboptimal composition of PN for 7 days and then infused with either saline or lipopolysaccharide (LPS) for 9 hours to induce an acute-phase reaction. Abdominal tissue edema and blood markers of immunity, inflammation, and oxidative stress were assessed.Piglets receiving suboptimal nutrition showed signs of malnutrition with restricted growth, signs of inflammation (elevated C-reactive protein [CRP], interleukin-6, and serum amyloid A levels), oxidative stress (lower erythrocyte glutathione/hemoglobin and α-tocopherol/cholesterol ratios), and liver dysfunction (increased liver weight and blood bilirubin levels). Perirenal edema was more excessive in malnourished LPS-infused animals, relative to healthy LPS-infused control animals (P < .01). Malnutrition reduced the inflammatory response to LPS (lower CRP, tumor necrosis factor-α, haptoglobin, and neutrophil to lymphocyte ratio) but did not influence LPS-induced oxidative stress markers.We conclude that endotoxemia and malnutrition in combination lead to acute-phase hyporesponsiveness and perirenal edema in piglets. This finding may have implications for pediatric patients that suffer from malnutrition, as their response to bacterial infections may differ substantially from patients of normal nutrition status.
2019Inflammation in gastrointestinal disorders: prevalent socioeconomic factors.Clin Exp GastroenterolWestern populations harbor a chronic inflammation pattern that lacks organ cardinal signs (edema, increased temperature, pain, and impaired function), releases increased levels of C-reactive protein, and often runs a creeping clinical course with generalized debilitating disease superimposed on system-specific involvement, mostly including nervous tissue (multiple sclerosis, Parkinson's syndromes), joints (arthritis), and skin (psoriasis). A finalistic interpretation may apply to the consideration of the gut as the source of inflammation. In fact, these kind of local events as well as the remote manifestations named above, could be conditioned by the microbiome, the huge cell population indwelling the gut which is under growing scrutiny. The role of the gut as a barrier organ justifies lingering submucosal inflammation as a patrolling activity to maintain bodily integrity; the microbiome, launching inflammogenic signals in response to abrupt diet changes, confers to gut inflammation a socioeconomic vector calling for hitherto unrecognized multi-disciplinary interventions.
2019Renal Pathologic Findings in TAFRO Syndrome: Is There a Continuum Between Thrombotic Microangiopathy and Membranoproliferative Glomerulonephritis? A Case Report and Literature Review.Front ImmunolTAFRO syndrome is a clinical subtype of idiopathic multicentric Castleman disease (iMCD) that is characterized by thrombocytopenia, anasarca, fever and/or elevated serum C-reactive protein, renal dysfunction, and organomegaly. A 28-year-old woman with fever, weight gain of 13 kgs, lower extremity edema, hepatosplenomegaly, and multicentric peripheral lymphadenopathy was referred to our center. Laboratory investigations revealed anemia, thrombocytopenia, creatinine at 1.19 mg/dL and hypoalbuminemia at 33 g/L. Proteinuria was measured at 2 g/day including albuminuria at 1.5 g/day. Urinary sediment examination found leukocyturia at 44,000/mL and hematuria at 645,000/mL. Vascular endothelial growth factor (VEGF) level was elevated. A cervical lymph node biopsy found features consistent with the mixed histopathological subtype of iMCD. A renal biopsy revealed a membranoproliferative glomerulonephritis (MPGN) pattern. We initiated 3 days of methylprednisolone pulse-therapy at 1,000 mg per day, followed by prednisone 1 mg/kg/day and evolution was favorable. 19 iMCD patients with TAFRO syndrome had undergone a renal biopsy: 8 cases with author's diagnosis consistent with MPGN-like and 11 cases of thrombotic microangiopathy (TMA)-like glomerulopathy without fibrin thrombi in glomerular capillaries or arterioles and without typical biological signs. Clinical, biological, and outcome characteristics were similar between the cases described as having MPGN and TMA-like presentation. After a thorough review of histopathological descriptions for each case, MPGN lesions seems to be the consequences of chronic glomerular endothelial injury in persistent TMA. We suspect that VEGF and IL-6 play a key role in the physiopathology of the spectrum of renal involvement from TMA-like to MPGN observed in TAFRO syndrome. We present a Caucasian iMCD patient with TAFRO syndrome with renal insufficiency secondary to MPGN, which might be secondary to a chronic TMA-like disease. We suspect that there is a continuum between TMA and MPGN lesions in TAFRO syndrome favored by VEGF and IL-6.
2019Zinc Gluconate-Loaded Chitosan Nanoparticles Reduce Severity of Collagen-Induced Arthritis in Wistar Rats.ACS Biomater Sci EngRheumatoid arthritis (RA) is the most prevalent autoimmune disease affecting about 1% world population. Zinc (Zn) is necessary for the maintenance of bone homeostasis and the level of Zn was reported to be decreased in RA patients and collagen-induced arthritic rats. Effective delivery of Zn has been reported using zinc gluconate but oral absorption of Zn from zinc gluconate (ZG) is very low in humans. Zn supplementation reduces disease severity in patients suffering from chronic, refractory RA and exerts mild and transient side effects. The aim of this study was to synthesize and characterize zinc gluconate-loaded chitosan nanoparticles (ZG-Chit NPs) and to evaluate and compare therapeutic efficacy of ZG-Chit NPs and zinc gluconate against collagen-induced RA in Wistar rats. The nanoparticles were formulated by ionic gelation method and the hydrodynamic diameter was 106.5 ± 79.55 nm as measured using DLS. The particle size, shape, and surface morphology was further confirmed by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. These nanoparticles showed good cytocompatibility against foreskin fibroblasts (BJ) and L929 cells. Arthritic rats were treated with ZG (20 mg/kg body weight, intraperitoneally) and equivalent doses of ZG-Chit NPs. The treatment of both ZG and ZG-Chit NPs reduced the severity of arthritis as evidenced by reduced joint swelling, erythema, and edema but ZG-Chit NPs exhibited superior efficacy. Furthermore, it was found that ZG and ZG-Chit NPs attenuate biomarkers of inflammation (C-reactive protein, myeloperoxidase, nitric oxide, TNF-α, and IL-1β) and oxidative stress (articular elastase, lipid peroxidation, catalase, glutathione, and superoxide dismutase). The results of the histopathology further confirmed that ZG-Chit NPs markedly suppressed infiltration of inflammatory cells as compared to ZG at the ankle joint tissue. Immunohistochemical analysis also revealed that treatment with ZG-Chit NPs resulted in reduced pro-inflammatory marker (TNF-α, IL-6, and iNOS) expression and enhanced SOD1 expression. Overall, this study suggests that ZG and ZG-Chit NPs suppressed the severity of arthritis plausibly mediated by attenuation of inflammation and oxidative stress and more importantly ZG-Chit NPs exhibited superior efficacy as compared to ZG.
2019Induction of Chronic Subclinical Systemic Inflammation in Sprague-Dawley Rats Stimulated by Intermittent Bolus Injection of Lipopolysaccharide.Arch Immunol Ther Exp (Warsz)Chronic subclinical systemic inflammation has a key role in stimulating several chronic conditions associated with cardiovascular diseases, cancer, rheumatoid arthritis, diabetes, and neurodegenerative diseases. Hence, developing in vivo models of chronic subclinical systemic inflammation are essential to the study of the pathophysiology and to measure the immunomodulatory agents involved. Male Sprague-Dawley rats were subjected to intraperitoneal, intermittent injection with saline, or lipopolysaccharide (LPS) (0.5, 1, 2 mg/kg) thrice a week for 30 days. Hematological, biochemical, and inflammatory mediators were measured at different timepoints and at the end of the study. The hearts, lungs, kidneys, and livers were harvested for histological evaluation. Significant elevation in peripheral blood leukocyte includes neutrophils, monocytes, and lymphocytes, as well as the neutrophils-to-lymphocyte ratio. The pro-inflammatory mediator levels [C-reactive protein, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8] along with the biochemical profile (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, creatinine, and urea) were increased significantly (P < 0.05) and increased the expression of monocyte chemoattractant protein-1 and TNF-β. The histopathological changes of heart, lung, kidney, and liver tissues revealed degeneration, cellular infiltration of leukocyte in the inflammatory foci and interstitial space, edema, early signs of fibrosis, apoptosis, and necrosis. In conclusion, these results indicate that intermittent exposure to LPS produces chronic subclinical systemic inflammation in multiple organs leading to chronic conditions and supports this model to be a useful preclinical tool for developing immunotherapeutic agents that could prevent, or reduce, chronic inflammatory diseases associated with, or without, bacterial translocation.
2019Characterization of the Obese Phenotype of Heart Failure With Preserved Ejection Fraction: A RELAX Trial Ancillary Study.Mayo Clin ProcTo characterize the obese heart failure with preserved ejection fraction (HFpEF) phenotype in a multicenter cohort.This was a secondary analysis of the randomized clinical trial RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) performed between October 1, 2008, and February 1, 2012. Patients with HFpEF were classified by body mass index (BMI) as obese (BMI≥35 kg/m) and nonobese (BMI<30 kg/m) for comparison.Obese patients with HFpEF (n=81) were younger (median age, 64 [interquartile range (IQR), 67-79] years vs 73 [IQR, 56-70] years; P<.001) but had greater peripheral edema (31% [25] vs 9% [6]; P<.001), more orthopnea (76% [56] vs 53% [35]; P=.005), worse New York Heart Association class (P=.006), and more impaired quality of life (P<.001) as compared with nonobese patients with HFpEF (n=70). Despite more severe signs and symptoms, obese patients with HFpEF had lower N-terminal pro B-type natriuretic peptide level (median, 481 [IQR, 176-1183] pg/mL vs 825 [IQR, 380-1679] pg/mL [to convert to pmol/L, multiply by 0.118]; P=.007) and lower left atrial volume index (median, 38 [IQR, 31-47] mL/m vs 54 [IQR, 41-63] mL/m; P<.001). Serum C-reactive protein (median, 5.0 [IQR, 2.4-9.9] mg/dL vs 2.7 [IQR, 1.6-5.4] mg/dL [to convert to mg/L, multiply by 10]; P<.001) and uric acid (median, 7.8 [IQR, 6.1-8.7] mg/dL vs 6.8 [IQR, 5.5-8.3] mg/dL; P=.03) levels were higher in obese HFpEF, indicating greater systemic inflammation, than in nonobese HFpEF. Peak oxygen consumption was impaired in obese HFpEF (median, 11.1 [IQR, 9.6-14.4] mL/kg per minute vs 13.1 [IQR, 11.3-14.7] mL/kg per minute; P=.008), as was submaximal exercise capacity (6-minute walk distance, 272 [IQR, 200-332] m vs 355 [IQR, 290-415] m; P<.0001).Obese HFpEF is associated with decreased quality of life, worse symptoms of heart failure, greater systemic inflammation, worse exercise capacity, and higher metabolic cost of exertion as compared with nonobese HFpEF. Further study is required to understand the pathophysiology and potential distinct treatments for patients with the obese phenotype of HFpEF.clinicaltrials.gov Identifier: NCT00763867.
2019Clinical manifestations of respiratory syncytial virus-associated encephalopathy in Fukushima, Japan.Pediatr IntWe investigated the epidemiology and clinical course of children with respiratory syncytial virus (RSV)-associated encephalopathy.We retrospectively collected data for 280 patients from a questionnaire survey of acute encephalitis/encephalopathy (AE/E) in Fukushima Prefecture. We enrolled six patients diagnosed with RSV-associated encephalopathy from these 280 patients, and retrospectively investigated the clinical features and prognosis.Six (2.1%) of the 280 patients with AE/E were found to have RSV-associated encephalopathy. The age at onset and male-to-female ratio were 1.3 ± 0.5 years and 2:4, respectively. The mean duration of fever and the duration of loss of consciousness were 3.7 ± 1.5 days (range, 2-6 days), and 3.3 ± 2.3 days (range, 2-8 days), respectively. Four patients had leukocytosis and two patients had high serum C-reactive protein. On admission, one child presented with normal renal and hepatic function, but, high serum ferritin, renal and hepatic dysfunction, and disseminated intravascular coagulation were observed along with progressive multiple organ failure, with the patient dying on the second day of hospitalization. On computed tomography of the brain, five patients had brain edema and one patient had a low-density area. Two of the six children had sequelae while three children had no sequelae.The incidence of RSV-associated encephalopathy in all AE/E patients was 2.1% Given that half of the children with RSV-associated encephalopathy had sequelae or death, the prognosis for RSV-associated encephalopathy is not particularly good and it is necessary to pay careful attention to patients with RSV-associated encephalopathy.
2019Correlates of Gut Function in Children Hospitalized for Severe Acute Malnutrition, a Cross-sectional Study in Uganda.J Pediatr Gastroenterol NutrChildren with severe acute malnutrition (SAM) may have impaired intestinal function, which can result in malabsorption, diarrhoea, and poor growth. This study evaluated the gut function of children with SAM using fecal and blood biomarkers and assessed their correlates.A cross-sectional study, nested in a randomized trial (www.isrctn.com, ISRCTN 16454889), was conducted at Mulago hospital, Uganda among subgroups of 400 children with complicated SAM and 30 community controls. Gut function was evaluated by 5 biomarkers: plasma citrulline, fecal myeloperoxidase and fecal neopterin, bacterially derived 16S rRNA gene and internal transcribed Spacer region (ITS) specific for Candida spp. in blood.Compared with controls, children with SAM had lower median plasma citrulline (5.14 vs 27.4 μmol/L, P < 0.001), higher median fecal myeloperoxidase (18083 vs 7482 ng/mL, P = 0.001), and fecal neopterin (541 vs 210 nmol/L, P < 0.001). A higher blood concentration of 16S rRNA gene copy numbers was observed among children with SAM (95 vs 28 copies/μl, P = 0.05), whereas there was no difference in the blood concentration of Candida-specific ITS fragment.Among those with SAM, plasma citrulline was lower in children with edema, diarrhoea, dermatosis, and plasma C-reactive protein (CRP) >10 mg/L. Fecal neopterin was positively correlated with symptoms of fever and cough whereas it was negatively correlated with mid-upper arm circumference (MUAC), weight-for-height z score (WHZ), edema, and dermatosis.Children with complicated SAM seem to have impaired gut function characterized by reduced enterocyte mass, intestinal inflammation, and increased bacterial translocation.
2019Effect of Dexketoprofene Trometamol on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.J Coll Physicians Surg PakTo evaluate the efficacy of dexketoprofene trometamol solution following the administration of contrast agent for Endoscopic Retrograde Cholangiopancreatography (ERCP) in decreasing the rate of pancreatitis, in experimental rat model.Experimental study.Faculty of Medicine, Research and Animal Laboratory of Bezmialem University, Istanbul, Turkey in January 2018.Forty Wistar-Albino® male rats of 250-300g were divided into 4 equal groups. Group I underwent cannulation; group II had cannulation with saline; group III had cannulation and contrast agent; group IV had cannulation with contrast agent and dexketoprofene trometamol intra-muscular (IM). Twenty four hours following the procedure, the rats were sacrified and pancreatic tissues were examined histopathologically, with evaluation of blood levels of leukocyte, glucose, SGOT, LDH, amylase, and C-reactive protein (CRP) level. Histopathological grading of acute pancreatitis was performed using haematoxylin and eosin staining.Mean levels of amylase and leukocyte were found to be significantly higher in groups II, III, IV when compared to group I (p=0.001). CRP level was found to be highest in group III (p=0.001). Histopathological grade of pancreatitis was found to be significantly higher in groups II, III, IV than group I (p: 0.001, 0.001, 0.028, and 0.001, respectively). Scores of edema, acinar necrosis, inflammation and perivascular infiltration of group III were higher than in group IV (p=0.001).Intra-muscular administration of dexketoprofen trometamol during ERCP procedure may be beneficial in decreasing the rate of post-ERCP pancreatitis, as shown by histopathological and laboratory profile.
2019[Clinical value of early liquid resuscitation guided by passive leg-raising test combined with transthoracic echocardiography in patients with septic shock].Zhonghua Wei Zhong Bing Ji Jiu Yi XueTo explore the clinical value of early fluid resuscitation guided by passive leg-raising test (PLR) combined with transthoracic echocardiography (TTE) in patients with septic shock.A prospective randomized controlled trial (RCT) was conducted. Seventy-four patients with septic shock admitted to China-Japan Friendship Hospital from January 2017 to October 2018 were enrolled. The patients were randomly divided into control group and experimental group with 37 patients in each group. Both groups of patients were treated with broad-spectrum antibiotics empirically, while received fluid resuscitation via the subclavian vein catheter. The patients of control group were given rapid fluid replacement, and those of experimental group received fluid replacement according to result of PLR combined with TTE. The stroke volume (SV) was measured by TTE before and after PLR, volumetric response of patients was judged by stroke volume variation (SVV). If the SVV ≥ 15%, it was considered that there was a volume responsiveness, and fluid loading was given. If SVV < 15%, it was considered that there was no volume shortage, and the restrictive fluid replacement was given. The goal of fluid resuscitation in both groups were to simultaneously meet the central venous pressure (CVP) of 8-12 mmHg (1 mmHg = 0.133 kPa), mean arterial pressure (MAP) ≥ 65 mmHg, urine volume ≥ 0.5 mL×kg×h, and central venous blood oxygen saturation (ScvO) ≥ 0.70 within 6 hours. Vasoactive drugs were used when the patients could not achieve the treatment goals. The MAP, lactic acid (Lac), oxygenation index (PaO/FiO) and ScvO of the patients were determined at 6 hours of treatment, and serum C-reactive protein (CRP) and chest CT were reviewed at 48 hours of treatment, and compared with those before treatment. The total hospital stay and the mortality were recorded.There was no significant difference in gender, age, body weight and etiological structure between the two groups, which indicated that the baseline data were generally balanced. There was no statistical difference in MAP, Lac, PaO/FiO, ScvO and CRP before infusion between the two groups. After 6 hours of treatment, the MAP, Lac, PaO/FiO and ScvO of the two groups were all better than those before infusion. Except for the difference in MAP between the experimental group and the control group (mmHg: 78.76±5.22 vs. 76.35±6.66, P > 0.05), the other three parameters in the experimental group were significantly better than those in the control group [Lac (mmol/L): 2.52±1.15 vs. 3.89±1.42, PaO/FiO (mmHg): 338.14±27.47 vs. 303.35±22.52, ScvO: 0.70±0.04 vs. 0.63±0.05, all P < 0.01]. After 48 hours of treatment, CRP levels of both groups were lower than those before infusion, and the experimental group was better than the control group (mg/L: 110.12±39.80 vs. 137.98±31.23, P < 0.01). Chest CT showed that the incidence of pulmonary edema in the experimental group was significantly lower than that in the control group [13.5% (5/37) vs. 37.8% (14/37), P < 0.01]. The hospital stay of the experimental group was shorter than that of the control group (days: 21.47±5.58 vs. 28.33±4.93, P < 0.01), but no significant difference in mortality was found between the two groups [18.9% (7/37) vs. 18.9% (7/37), P > 0.05].Compared with the traditional rapid fluid replacement, early fluid resuscitation treatment strategies guided by the PLR combined with TTE, could better improve perfusion and oxygenation level of tissues and organs, avoid pulmonary edema caused by rapid fluid replacement, shorten the hospital stay in patients with septic shock, but had no significant effect on hospital mortality.
2019Myeloid-Related Protein 8/14 Participates in the Progression of Experimental Pneumococcal Meningitis by Augmentation of Inflammation.J Mol NeurosciIt has been reported that myeloid-related protein 8/14 (MRP8/14) participates in the progression of inflammation after release from neutrophils and monocytes. This study aimed to clarify the mechanism(s) of the MRP8/14-augmented inflammatory response in mice with pneumococcal meningitis. Streptococcus pneumoniae (SP) meningitis was established by intracerebral injection of SP suspension. Balb/c mice were randomly divided into four groups and received the following injections: phosphate-buffer saline (PBS), MRP8/14 alone, SP alone, and SP plus MRP8/14. At 6 h, 24 h and 48 h postinfection, the clinical disease status was measured by the modified neurological severity score test, body weight loss and degree of cerebral edema; mice were anaesthetized, blood samples and brain samples were collected and brain inflammation was detected by haematoxylin and eosin (HE) staining; tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) levels in serum and brain homogenates were assessed by an enzyme-linked immunosorbent assay (ELISA), and the mRNA levels of the above cytokines in brain homogenates were measured by polymerase chain reaction (PCR); and the expression of nuclear factor-kappa B (NF-κB) p65 in brain tissues was determined by immunohistochemical assay. In this study, we identified that MRP8/14 substantially augmented the SP-stimulated inflammatory response, aggravated clinical disease status and exacerbated SP-induced brain edema in a murine model of pneumococcal meningitis. Exogenous administration of MRP8/14 significantly enhanced mRNA and protein expression of the proinflammatory cytokines and chemokines TNF-α, CRP, IL-6 and MCP-1 in brain homogenates and serum from mice with pneumococcal meningitis, which may be related to the NF-κB signalling pathway. We further found that MRP8/14 strongly augmented SP-induced phosphorylation of NF-κB p65 in brain tissue slices from the same model. In conclusion, our results indicated that MRP8/14 augmented the inflammatory response in mice with pneumococcal meningitis and contributed to the development of disease, which was probably through NF-κB signalling pathway activation.
2019Biomarkers of Cerebral Damage in Fatal Hypothermia: Preliminary Results.Am J Forensic Med PatholThe identification of hypothermia as the cause of death remains challenging in forensic pathology because of unspecific radiological, morphological, and biochemical results. Hyperemia, edema, and petechial hemorrhages within the cerebral parenchyma were described in cases of death by hypothermia. On the other hand, the effect of low temperatures in the brain has been speculated to cause local injuries on a cellular level with potential occurrences of necrosis and inflammation. In the study herein described, endocan, alkaline phosphatase, neuron-specific enolase, S100 protein subunit B, glial fibrillary acidic protein, and C-reactive protein were measured in postmortem serum from femoral blood and cerebrospinal fluid in a series of hypothermia fatalities and control cases. The combination of data collected failed to identify a specific biochemical profile for death by hypothermia in postmortem serum and/or the cerebrospinal fluid, thus suggesting that an alternative panel of brain damage biomarkers indicative of diffuse hypoxic brain injury needs to be defined in hypothermia fatalities.
2019Protective Effects of Erythropoietin towards Acute Lung Injuries in Rats with Sepsis and Its Related Mechanisms.Ann Clin Lab SciThe aim of this study was to explore the effects of erythropoietin (EPO) in acute lung injuries in rats with sepsis. 127 male SD rats were divided into 3 groups (n=8): group Sham, group ALI (sepsis-caused lung injury), group EPO (EPO intervention). The blood gas analysis, C-reactive protein level (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10 were detected and compared. The water content fraction and myeloperoxidase (MPO) activities, apoptosis, and expression level of nuclear factor -κB (NF-κB p65) in lung tissues were also detected. Compared to group Sham, the oxygenation index of group ALI was decreased (140.66±12.82 vs. 194.7±16.36), CRP (peak value: 2.31±0.33 mg/L vs. 1.00±0.16 mg/L), IL-10 (peak value: 711.26±84.97 ng/L vs. 51.21±11.45 ng/L), TNF-a (63.69±6.85 ng/L vs. 12.92±0.91 ng/L), and IL-6 (peak value: 1768.93±195.11 ng/L vs. 68.71±11.48 ng/L) increased (<0.01), and the lung cell apoptosis and expression of NF-κB p65 (302.75±51.38 vs. 121.46±11.79) were also increased (<0.01), and there was a recovery of EPO group (<0.01). Group ALI exhibited pulmonary interstitial and alveolar edema, hemorrhage, and lung collapse, but the EPO intervention significantly reduced the above lung pathological changes (the water content was 70.36±1.24% in Sham group, 84.26±3.07% in ALI group and 75.72±1.96% in EPO group, <0.01; MPO: 2.23±0.67, 7.56±1.02, 5.73±0.86, <0.01; apoptotic index: 3.73±0.39, 25.69±4.54, 9.59±2.59, <0.01). EPO could inhibit the expression of NF-κB in lung tissues, inhibit the levels of proinflammatory cytokines TNF-a and IL-6, but improve the level of anti-inflammatory cytokine IL-10, thus reducing the pathological changes of lung tissues and producing protective effects towards lung tissues.
2019Serum fetuin-A, tumor necrosis factor alpha and C-reactive protein concentrations in patients with hereditary angioedema with C1-inhibitor deficiency.Orphanet J Rare DisHereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is characterized by localized, non-pitting, and transient swelling of submucosal or subcutaneous region. Human fetuin-A is a multifunctional glycoprotein that belongs to the proteinase inhibitor cystatin superfamily and has structural similarities to the high molecular weight kininogen. Fetuin-A is also known a negative acute phase reactant with anti-inflammatory characteristics. In this study we aimed to determine serum fetuin-A, C-reactive protein (CRP) and tumor necrosis factor alpha (TNFα) concentrations in patients with C1-INH-HAE during symptom-free period and during attacks and compare them to those of healthy controls. Further we analyzed possible relationship among these parameters as well as D-dimer levels which was known as marker of HAE attacks.Serum samples of 25 C1-INH-HAE patients (8 men, 17 women, age: 33.1 ± 6.9 years, mean ± SD) were compared to 25 healthy controls (15 men, 10 women, age: 32.5 ± 7.8 years). Serum fetuin-A and TNFα concentrations were determined by ELISA, CRP and D-dimer by turbidimetry.Compared to healthy controls patients with C1-INH-HAE in the symptom-free period had significantly decreased serum fetuin-A 258 μg/ml (224-285) vs. 293 μg/ml (263-329), (median (25-75% percentiles, p = 0.035) and TNFα 2.53 ng/ml (1.70-2.83) vs. 3.47 ng/ml (2.92-4.18, p = 0.0008) concentrations. During HAE attacks fetuin-A levels increased from 258 (224-285) μg/ml to 287 (261-317) μg/ml (p = 0.021). TNFα and CRP levels did not change significantly. We found no significant correlation among fetuin-A CRP, TNFα and D-dimer levels in any of these three groups.Patients with C1-INH-HAE have decreased serum fetuin-A concentrations during the symptom-free period. Given the anti-inflammatory properties of fetuin-A, the increase of its levels may contribute to the counter-regulation of edema formation during C1-INH-HAE attacks.
2019ERAMRS: a new MR scoring system for early rheumatoid arthritis of the wrist.Eur RadiolTo (i) devise a new semi-quantitative scoring system known as Early Rheumatoid Arthritis Magnetic Resonance Score (ERAMRS) to assess inflammation of the wrist on magnetic resonance imaging in early rheumatoid arthritis and to (ii) test ERAMRS and other MR scoring systems against everyday used clinical scorings.One hundred six treatment-naïve patients (81 females, 25 males, mean age 53 ± 12 years) with early rheumatoid arthritis (ERA) underwent clinical/serological testing as well as 3-T MRI examination of the most symptomatic wrist. Clinical assessment included Disease Activity Score-28 and Health Assessment Questionnaire; erythrocyte sedimentation rate and C-reactive protein were measured. MR imaging data was scored in all patients using three devised MR semi-quantitative scoring systems, namely, the (a) ERAMRS system, (b) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) system, and the (c) McQueen Score system.Synovitis was present in 106 (100%), tenosynovitis in 98 (92%), and bone marrow edema in 84 (79%) of 106 ERA wrists. ERAMRS had the highest correlation with clinical disease activity scores (r = 0.476, p < 0.001) and serological parameters (r = 0.562, p < 0.001). RAMRIS system had the lowest correlation (r = 0.369, p < 0.001 for clinical disease activity; r = 0.436, p < 0.001 for serological parameters). RAMRIS synovitis subscore had a lower correlation than ERAMRS for clinical disease activity (r = 0.410, p < 0.001) and for serological parameters (r = 0.456, p < 0.001).The ERAMRS system, designed to grade inflammation on wrist MRI in ERA, provided the best correlation with all clinical scoring systems and serological parameters, indicating its improved clinical relevance over other MR scoring systems.• We devised a clinically relevant, easy-to-use semi-quantitative scoring system for scoring inflammation on MRI of the wrist in patients with early rheumatoid arthritis. • ERAMRS system showed better correlation with all clinical and serological assessment of inflammation in patients with early rheumatoid arthritis indicating its improved clinical relevance over other MR scoring systems.
2019Separating Acute Rheumatic Fever from Nonrheumatic Streptococcal Myocarditis.Case Rep MedStreptococcal pharyngitis has been historically complicated with systemic involvement manifesting as acute rheumatic fever, which is a serious condition that can lead to permanent damage to heart valves. A recent association between streptococcal pharyngitis and nonrheumatic heart disease is emerging in literature. We present a case of nonrheumatic streptococcal myocarditis diagnosed using cardiac MRI.A 25-year-old male, presented with complaints of sore throat, nonproductive cough, fever, pleuritic chest pain, and progressive dyspnea for four days. The patient had elevated troponins at presentation of 0.47 (ng/L) that peaked at 4.0 (ng/L). ECG showed sinus rhythm and ST elevations in leads V2, V3, V4, and V5. NT-Pro-BNP was 1740. Transthoracic echocardiogram (TTE) showed reduced ejection fraction (EF) of 37% and global hypokinesis. The rapid strep test was positive for group A streptococcus and C-reactive protein was elevated at 161. Cardiac MRI demonstrated an EF of 53% and edema in the anterior wall without delayed gadolinium enhancement. Cardiac catheterization showed normal coronaries.According to modified Jones criteria, the patient did not meet the full major or minor criteria to be diagnosed with acute rheumatic fever. The course of the nonrheumatic myocarditis is favorable and includes a full recovery of cardiac function, no involvement of cardiac valves, or long-term use of antibiotics.It is crucial to make a separate distinction between acute rheumatic fever and nonrheumatic myocarditis because this will have huge implications on management and long-term use of antibiotics. Cardiac imaging modalities can aid in distinction between the two disease entities.
2020Early Peritoneal Dialysis Ameliorates Blast Lung Injury by Alleviating Pulmonary Edema and Inflammation.ShockBlast lung injury is a high-energy trauma with high mortality for explosion victims. A treatment for blast lung injury is still lacking. The aim of this study was to observe the efficacy and mechanism of peritoneal dialysis combined with glucocorticoids (GC) in the treatment of blast lung injury in rats.Rats were randomly divided into five groups: control, sham, GC, peritoneal dialysis (dialysis for short), and dialysis + GC groups. All rats were injured by a biological shock tube-I.The lung water levels in the dialysis group and dialysis + GC group were significantly lower than that in the control group at 6 and 24 h after blast injury. The oxygenation index, forced vital capacity, maximum midexpiratory flow, and functional residual capacity of rats in the dialysis and dialysis + GC groups were significantly higher than those in the control group. The serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor- α, monocyte chemoattractant protein-1, C-reactive protein, and IL-10 in the dialysis and dialysis + GC groups were significantly lower than those in the control group. Genome-wide mRNA microarray results showed that the aquaporin 1 level in the lung tissue of the dialysis group was 6.67 times higher than that in the control group.Early peritoneal dialysis can attenuate pulmonary edema and inflammation, and protect acute lung injury after blast injury.
2019Effect of Magnetic Resonance Imaging vs Conventional Treat-to-Target Strategies on Disease Activity Remission and Radiographic Progression in Rheumatoid Arthritis: The IMAGINE-RA Randomized Clinical Trial.JAMAWhether using magnetic resonance imaging (MRI) to guide treatment in patients with rheumatoid arthritis (RA) improves disease activity and slows joint damage progression is unknown.To determine whether an MRI-guided treat-to-target strategy vs a conventional clinical treat-to-target strategy improves outcomes in patients with RA in clinical remission.Two-year, randomized, multicenter trial conducted at 9 hospitals in Denmark. Two hundred patients with RA in clinical remission (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] <3.2 and no swollen joints) were enrolled between April 2012 and June 2015. The final follow-up visit was April 2017.Patients were randomly allocated (1:1) to an MRI-guided vs a conventional treat-to-target strategy. In the MRI-guided group, the treatment goal was absence of MRI bone marrow edema combined with clinical remission, defined as DAS28-CRP of 3.2 or less and no swollen joints. In the conventional group, the treatment goal was clinical remission.Co-primary outcomes were proportions of patients achieving DAS28-CRP remission (DAS28-CRP <2.6) and with no radiographic progression (no increase in total van der Heijde-modified Sharp score) at 24 months. Significance testing for the primary outcome was based on 1-sided testing. Secondary outcomes were clinical and MRI measures of disease activity, physical function, and quality of life.Of 200 patients randomized (133 women [67%]; mean [SD] age, 61.6 [10.5] years; median baseline DAS28-CRP, 1.9 [interquartile range, 1.7-2.2]; van der Heijde-modified Sharp score, 18.0 [interquartile range, 7.0-42.5]), 76 patients (76%) in the MRI-guided group and 95 (95%) in the conventional group completed the study. Of these, 64 (85%) vs 83 (88%), respectively, reached the primary clinical end point (risk difference, -4.8% [1-sided 95% CI, -13.6% to + ∞; 1-sided P = .19]) and 49 (66%) vs 58 (62%), respectively, reached the primary radiographic end point (risk difference, 4.7% [1-sided 95% CI, -7.0% to + ∞; 1-sided P = .25). Of 10 key secondary end points, 8 were null and 2 showed statistically significant benefit for the MRI treat-to-target group. Seventeen patients (17%) in the MRI-guided treat-to-target group and 6 patients (6%) in the conventional treat-to-target group experienced serious adverse events.Among patients with RA in clinical remission, an MRI-guided treat-to-target strategy compared with a conventional treat-to-target strategy did not result in improved disease activity remission rates or reduce radiographic progression. These findings do not support the use of an MRI-guided strategy for treating patients with RA.ClinicalTrials.gov Identifier: NCT01656278.
2019The value of the simplified RAMRIS-5 in early RA patients under methotrexate therapy using high-field MRI.Arthritis Res TherThe aim of the study was to evaluate a simplified version of the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) for five joints of the hand (RAMRIS-5) in patients with early rheumatoid arthritis (RA) before and after the initiation of methotrexate (MTX) therapy using high-resolution, 3-T magnetic resonance imaging (MRI).Twenty-eight patients with a seropositive, early RA (disease duration of less than 6 months (range 2-23 weeks)) according to 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria (mean age 56.8 years, range 39-74) were prospectively assessed with a baseline investigation including clinical assessment (disease activity score of 28 joints (DAS-28) and C-reactive protein (CRP)) and 3-T MRI of the clinically dominant hand. Follow-up visits were performed 3 and 6 months after initiation of a MTX therapy at baseline. MRI scans were analyzed in accordance with RAMRIS and the simplified RAMRIS-5.DAS-28 and CRP decreased significantly after initiation of MTX therapy. Even though erosion scores increased over time, RAMRIS and RAMRIS-5 also decreased significantly after the start of therapy. There was a strong correlation between the total RAMRIS-5 and RAMRIS at baseline (r = 0.838; P <0.001) and follow-up (3 months: r = 0.876; P <0.001; 6 months: r = 0.897; P <0.001). In the short term (3-month follow-up), RAMRIS and RAMRIS-5 demonstrated similar ability to detect changes for all subgroups (bone edema, erosion, and synovitis). In the long-term comparison (6-month follow-up), RAMRIS-5 also showed similar effectiveness when detecting changes in bone edema and erosion compared with RAMRIS. Deviations occurred regarding only synovitis, where change was slightly higher in RAMRIS-5: SRM (RAMRIS) = 0.07 ± 0.14; SRM (RAMRIS-5) = 0.34 ± 0.06.Three-Tesla MRI-based RAMRIS-5 is a simplified and resource-saving RAMRIS score which compares favorably with the RAMRIS when detecting changes in early RA. Even though there is a slight abbreviation between RAMRIS-5 and the original score regarding the change of synovitis, it may be used for diagnosis and therapy monitoring in follow-up evaluations.
2018Increased serum levels of MIC1/GDF15 correlated with bone erosion in spondyloarthritis: A pilot study.Medicine (Baltimore)To assess the association between growth differentiation factor-15 (GDF15) and radiographic features including bone marrow edema and bone erosion in Spondyloarthritis (SpA).Patients with SpA (n = 120) receiving treatment in the Guangdong General Hospital, China, between August 2012 and December 2016 were retrospectively included. Serum of patients and healthy controls (n = 30) were collected and GDF15 levels were measured using ELISA. Inflammation was assessed by C-reactive protein (CRP), and magnetic resonance imaging (MRI) of the sacroiliac joint using Spondyloarthritis Research Consortium of Canada score and a method of dichotomy to assess fat metaplasia, bone erosion, and ankylosis. Radiographs of the pelvis were scored using the modified New York (mNY) score.Serum GDF15 levels were higher in SpA patients compared to controls (503.52 ± 222.92 vs. 190.86 ± 104.18 pg/mL, P < .0001). Patients who suffered from bone erosion on MRI had higher levels of GDF15 (525.72 [186.33, 801.62]vs. 428.06 [255.15, 670.98] pg/mL, P = .0375). There was a positive correlation between serum GDF15 and CRP (r = 0.5442, P < .0001). Moreover, GDF15 levels were related to CRP levels (r = 0.5658, P < .0001) in those X-ray scores were III, according to 1984mNY criteria. Receiver operating characteristic (ROC) analysis showed that GDF15 levels above 501.98pg/mL could predict presence of bone erosion on MRI.The present study suggested that serum GDF15 levels are higher in SpA patients than in healthy controls. The GDF15 level was correlated with CRP and may be a surrogate biomarker in bone erosion.
2018[Progressive pseudorheumatoid dysplasia misdiagnosed as ankylosing spondylitis: a case report].Beijing Da Xue Xue Bao Yi Xue BanIn this study, we reported a case of progressive pseudorheumatoid dysplasia in Peking University Third Hospital. A 56-year-old male patient presented with hip joint pain for more than 40 years and multiple joints pain with limitation of movements of these joints for 28 years. This patient suffered from joint pain and impaired range of motion of the hip, knee, elbow and shoulder gradually, associated with difficulty in walking and inability to take care of himself. He was diagnosed with "femoral head necrosis" or "ankylosing spondylitis" in local hospitals, but the treatment of nonsteroidal antiinflammatory drugs (NSAIDs) and sulfasalazine was not effective. Up to the age of 14, the patient displayed normal physical development, with the highest height was about 158 cm, according to the patient recall. However, his height was 153 cm at present. There was no history of similar illness in any family member. Physical examinations descried limitation of movement of almost all joints. Enlargement and flexion deformity of the proximal interphalangeal (PIP) joints of the hands resulted in the claw hand appearance. Limited abduction and internal and external rotation of the shoulder and hip could be find. He had normal laboratory findings for blood routine test, biochemical indexes and acute phase reactants such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Furthermore, HLA-B27 and autoimmune antibodies such as rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody and antinuclear antibody (ANA) were all negative. X-ray of the hip showed loss of the joint space and irregularities of the femoral head, both femoral head were flattened, it could be see hyperplasia, osteophytes, bilateral femoral neck thicken, neck dry angle turned smaller. The radiological findings of the spinal vertebra indicated kyphosis deformity, narrowing of the intervertebral discs, vertebral syndesmophytes and flattening of the vertebra. However, there was no clues of bone marrow edema in the lumbar MRI. At last, genetic testing for the Wnt1-inducible signaling pathway protein 3 (WISP3) gene was done and indicated compound heterozygous mutations: 756C>G and c.866dupA. These two mutations were derived from the patient's mother and father (the patient's parents each had a heterozygous mutation). Two exons of the WISP3 gene had nucleotide changes leading to amino acid mutations. According to the patient's history, symptoms, physical examinations, radiological findings and genetic testing, the final definitive diagnosis was progressive pseudorheumatic dysplasia.
2018Systemic involvement in ACS: Using CMR imaging to compare the aortic wall in patients with and without acute coronary syndrome.PLoS OnePrevious studies have demonstrated that in acute coronary syndrome (ACS), plaque destabilization and vessel inflammation, represented by vessel edema, often occur simultaneously in multiple coronaries, as well as extend to the cerebrovascular system. Our aim was to determine whether the inflammatory vascular processes occurring within the coronaries during ACS extend simultaneously to the descending aorta.We prospectively enrolled 111 patients (56 ACS patients and 55 non-ACS patients with known coronary artery disease) to undergo cardiac magnetic resonance of the thoracic aortic wall at presentation and at three-month follow-up. The primary outcome was change in aortic wall area (AWA) and maximal aortic wall thickness (AWT) from baseline to three-month follow-up. Secondary outcomes were baseline and follow-up differences in AWA and AWT, and changes in C-reactive protein (CRP).There was a significant reduction in mean AWA (p = 0.01) and AWT (p = 0.01) between index and follow up scans in ACS group, with no significant changes in non ACS group (both p>0.1) and no difference between ACS and non-ACS groups (p = 0.22). There was no significant difference in AWA and AWT at baseline (p>0.36) and follow-up (p>0.2) between groups. There was a significant reduction in CRP in both groups (p<0.01), with higher reduction in ACS patients (p<0.01).There was a reduction in aortic wall size, aortic wall area, and aortic wall thickness in patients presenting with ACS, and no change in non-ACS patients. There were no interval between-group differences in these measurements. We observed a reduction in C-reactive protein in both groups, with higher reduction noted in ACS patients.
2019The Epidemiology of Micro-arteriovenous Fistulas in the Lower Legs.Ann Vasc SurgPatients presenting with edema, skin redness, pain, and itching in their lower legs are common and encountered often in daily practice. However, although commonly recognized diseases such as deep venous thrombosis, stasis dermatitis due to varicose veins, lymphedema, and cellulitis are diagnosed correctly in most cases, micro-arteriovenous fistulas (AVFs) may often be overlooked due to low awareness and rarity. This study was carried out to evaluate the prevalence of micro-AVF in patients presenting with foot skin symptoms.A total of 134 patients (184 limbs) visited the Department of Vascular Surgery at Kesennuma City Hospital with edema, skin redness, pain, and itching in their lower legs from January to September 2017 and were enrolled and followed up until November 2017. All patients received ultrasonic inspection of their symptomatic limb, and a blood test (white blood cell count, C-reactive protein, and d-dimer) was performed if needed. When micro-AVF was detected in one limb, the other limb was routinely inspected by ultrasonography. A computed tomography scan was performed with the patient's consent. Patients diagnosed with micro-AVF started compression therapy immediately and were followed up for at least 2 months. A surgical procedure was considered if the symptoms worsened.Micro-AVFs were detected in 24 limbs (13%, 24/184) of 14 patients (7 males and 7 females; age 70 ± 11.7 years). Four patients had unilateral skin symptoms with unilateral micro-AVFs and 7 patients had unilateral skin symptoms and bilateral micro-AVFs. Three patients had bilateral skin symptoms and bilateral micro-AVFs. Asymptomatic micro-AVFs were detected in 7 limbs. Subjective symptoms disappeared and skin appearance normalized in 14 limbs of 12 patients during the first 2 months with compression therapy only. Compression therapy was not effective in 3 limbs of 2 patients and they underwent vein ligation surgery. None of the patients had a surgical history or history of trauma in their lower legs.Among the lower legs presenting with skin symptoms, we detected micro-AVFs in 13% of limbs; therefore, micro-AVF of the lower leg is not as rare as previously thought. In addition, 10 of 14 patients (71%) had micro-AVFs of the lower leg bilaterally.
2018The role of serum procalcitonin in the differential diagnosis of pneumonia from pulmonary edema among the patients with pulmonary infiltrates on chest radiography.Medicine (Baltimore)The aim of this study is to evaluate the usefulness of serum procalcitonin (PCT) as a diagnostic biomarker for distinguishing pneumonia from pulmonary edema in patients presenting with pulmonary infiltrates on chest radiography.A comparative study was performed retrospectively in a university-affiliated hospital, from May, 2013 to April, 2015. Adult patients (≥18 years) who showed pulmonary infiltrates on chest radiography and had blood tests with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), PCT, and N-terminal pro-b-type natriuretic peptide (NT-proBNP) on admission were included in the study. Clinical parameters collected on admission were compared between the case group (n = 143) with pneumonia and the control group (n = 88) with pulmonary edema alone.During the study period, a total of 1217 patients were identified. Of them, a total of 231 patients were included in analyses based on exclusion criteria. In the multivariate logistic regression analysis, PCT ≥0.25 ng/mL, ESR ≥35 mm/h, CRP ≥18 mg/L, NT-proBNP ≤200 pg/mL, underlying neurologic diseases, fever, sputum, absence of cardiomegaly, and a low Charlson comorbidity index were independently associated with pneumonia. For this model, the sensitivity, specificity, positive predictive value, and negative predictive value in distinguishing between the 2 groups were 90.2%, 79.6%, 87.8%, and 83.3%, respectively, with an area under the curve of 0.93.This study suggests that the practical use of PCT in conjunction with clinical data can be valuable in the differential diagnosis of pulmonary infiltrates and guidance for clinicians to prevent antibiotic misuse.
2019Cold water immersion or LED therapy after training sessions: effects on exercise-induced muscle damage and performance in rats.Lasers Med SciCryotherapy and phototherapy have been suggested as recovery methods due to their anti-inflammatory effects. They may also induce mitochondrial biogenesis, thus favoring endurance training adaptation. The aim of this study was to evaluate the anti-inflammatory and ergogenic effects of phototherapy or cold water immersion (CWI) applied daily after exercise in rats. Thirty-five rats were divided into five groups: control (CO), non-exercised (CE), passive recovery (PR), cold water immersion (CWI), and LED therapy (LED). The CO and CE groups were not submitted to training; however, the CE were submitted to an exhaustion test after the training period. Low-intensity swimming training (21 sessions, 45 min) was performed followed by passive recovery (PR), CWI (10 °C, 5 min), or infrared irradiation (940 nm, 4 J/cm). Forty-eight hours after the final training session, the CE, PR, CWI, and LED animals were submitted to an exhaustion test. The animals were euthanized 24 h later and submitted to hematological, creatine kinase (CK), and C-reactive protein (PCR) analysis. Gastrocnemius and soleus muscles were submitted to histological analysis. No differences in blood cell counts, CK, and PCR were detected between groups. The CE group presented an increased number of areas with necrosis in the gastrocnemius and soleus muscles. The PR group presented the highest frequency of areas with edema and inflammation followed by CWI and LED groups. None of the recovery methods improved the performance in the exhaustion test. Successive applications of recovery methods do not improve exercise performance, but downmodulate the inflammation and prevent muscle necrosis.
2018Incidental F-FDG Uptake of the Pubic Ramus and Abdominal Muscles due to Athletic Pubalgia During Acute ProstatitisMol Imaging Radionucl TherA 23-year-old African native male patient presented with fever, lumbalgia and dysuria after returning from a trip to Togo. His physical examination revealed pain over the pubic symphysis and rectal tenderness on digital exam. The C-reactive protein (CRP) level was elevated along with positive blood and urinary cultures for methicillin-resistant . An magnetic resonance imaging that has been performed to rule out arthritis/osteomyelitis in the pubis revealed edema of the symphysis. An F-FDG positron emission tomography/computed tomography supported the diagnosis of prostate infection and showed a focal uptake of the pubic symphysis, with diffuse hyper-metabolism of the insertions of the rectus abdominis and longus adductor muscles, corresponding to athletic pubalgia. Fever and CRP responded rapidly to antibiotherapy.
2018The first case of thrombocytopenia, anasarca, fever, renal impairment or reticulin fibrosis, and organomegaly (TAFRO) syndrome with unilateral adrenal necrosis: a case report.J Med Case RepTAFRO syndrome, which was first reported in 2010 in Japan, is a relatively rare disease characterized by thrombocytopenia, anasarca, fever, renal impairment, reticulin fibrosis, and organomegaly. Although this disease is considered similar to multicentric Castleman disease, some of the clinical features, such as thrombocytopenia, are different from typical cases of multicentric Castleman disease. In addition, the etiology of TAFRO syndrome remains unknown and controversial. There have only been a few cases of TAFRO syndrome complicated with adrenal gland lesions, and all of them have had hemorrhagic involvement.This report describes the case of a 46-year-old Asian man who presented with fever, epigastric pain, and back pain for 1 month. A computed tomographic scan revealed ascites, mild lymphadenopathy, and left adrenal necrosis without hemorrhage. A blood test showed thrombocytopenia, anemia, and elevated C-reactive protein, alkaline phosphatase, and creatinine levels. Based on the edema, severe thrombocytopenia, fever, reticulin myelofibrosis shown by bone marrow biopsy, mild lymphadenopathy, and progressive renal insufficiency, we diagnosed this patient as having TAFRO syndrome. He was successfully treated by immediate administration of glucocorticoids and tocilizumab.There have been no previous reports of a case of TAFRO syndrome complicated with adrenal necrosis. Because the biopsy of the left adrenal gland revealed necrosis without any evidence of hemorrhage, we concluded that the unilateral adrenal necrosis in this case was caused by either ischemia from infarction or organomegaly itself under severe hypercytokinemia. This unusual clinical course is useful for further analysis of the etiology of TAFRO syndrome.
2018A Risk Stratification Model for Cardiovascular Complications during the 3-Month Period after Major Elective Vascular Surgery.Biomed Res IntThe Revised Cardiac Risk Index (RCRI) is an extensively used simple risk stratification tool advocated by the European Society of Cardiology and European Society of Anesthesiology (ESC/ESA).The aim of this study was to find the best model for predicting 3-month cardiovascular complications in elective major vascular surgical patients using preoperative clinical assessment, calculation of the RCRI and Vascular Physiological and Operative Severity Score for the enumeration of mortality and morbidity (V-POSSUM) scores, and the preoperative levels of N-terminal brain natriuretic peptide (NT pro-BNP), high-sensitivity troponin I (hs TnI), and high-sensitivity C-reactive protein (hs CRP).We included 122 participants in a prospective, single-center, observational study. The levels of NT pro-BNP, hs CRP, and hs TnI were measured 48 hours prior to surgery. During the perioperative period and 90 days after surgery the following adverse cardiac events were recorded: myocardial infarction, arrhythmias, pulmonary edema, acute decompensated heart failure, and cardiac arrest.During the first 3 months after surgery 29 participants (23.8%) had 50 cardiac complications. There was a statistically significant difference in the RCRI score between participants with and without cardiac complications. ROC analysis showed that a combination of RCRI with hs TnI has good discriminatory power (AUC 0.909, p<0,001). By adding NT pro-BNP concentrations to the RCRI+hs TnI+V-POSSSUM combination we obtained the model with the best predictive power for 3-month cardiac complications (AUC 0.963, p<0,001).We need to improve preoperative risk assessment in participants scheduled for major vascular surgery by combining their clinical scores with biomarkers. Therefore, it is possible to identify patients at risk of cardiovascular complications who need adequate preoperative diagnosis and treatment.
2018The efficacy and safety of Hanslim for obese patients: Study protocol for a multicenter, randomized, double-blind, multi-dose, placebo-controlled, phase IIb clinical trial.Medicine (Baltimore)This study aims to evaluate the efficacy, safety, and appropriate dose of Hanslim, a Korean traditional herbal medicine, for obese patients, when compared to a placebo.This study is a randomized, double-blinded, multicenter, multidose, placebo-controlled, phase IIb clinical trial. A total of 165 obese patients with a body mass index (BMI) of more than 30 kg/m or obese patients with a BMI of 27 to 29.9 kg/m and one or more risk factors such as hypertension, diabetes, or hyperlipidemia will be enrolled. Participants will be randomly assigned to 1 of 3 groups (high-dose, low-dose, or placebo) with a 1:1:1 allocation ratio and will have 4 scheduled visits during the 12-week treatment period. The participants will be administered 2 tablets of Hanslim or placebo, 2 times per day. The difference in the proportion of participants who lost weight by more than 5% from their baseline at 12 weeks compared to the placebo group will be examined as the primary efficacy outcome. Secondary efficacy outcomes include differences in body weight, BMI, body-fat percentage, fat mass, skeletal-muscle mass, edema index, waist circumference, hip circumference, waist-hip ratio, serum lipid, blood glucose, C-reactive protein, and total score of Korean version of obesity-related quality of life after 12 weeks of treatment. Adverse events, laboratory test results, vital sings, and electrocardiography will be recorded to evaluate safety.This is the first prospective clinical trial to explore the efficacy and safety of Hanslim for obese patients. If the results provide the appropriate dosage of Hanslim, this study would contribute to the confirmatory evidence for the use of Hanslim as a treatment for obesity needed to conduct a large-scale, phase III clinical trial. The results will be published in a peer-reviewed journal.Clinical Research Information Service, ID: KCT0002193. Registered on January 6, 2017. https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=7468.
2018A case of Graves' disease associated with membranoproliferative glomerulonephritis and leukocytoclastic vasculitis.J Pediatr Endocrinol MetabBackground The association of hyperthyroidism with renal disease is very rare and the importance of timely clinical recognition cannot be overemphasized. Case presentation An 11-year-old girl presented with gastrointestinal symptoms while hypertension, edema and abdominal pain were noticed on clinical examination. Laboratory investigation revealed: hemoglobin 9.4 (11.5-15.5) g/dL, total white cell count 16 (4.5-12)×109/L, platelets 247 (150-450)×109/L, C-reactive protein (CRP) 31.8 (<5) mg/L, blood urea nitrogen (BUN) 126 (13-43) mg/dL, creatinine 0.98 (0.53-0.79) mg/dL, albumin 25 (35-52) g/dL, complement factor C3 0.7 (0.9-1.8) g/L, complement factor C4 0.1 (0.1-0.4) g/L, tri-iodothyronine 6.5 (2.5-5.2) pg/mL, free thyroxine 2.4 (1-1.7) ng/dL, thyroid stimulating hormone (TSH) <0.02 (0.5-4.3) mU/L. Urinalysis showed nephrotic range proteinuria. Renal function deteriorated necessitating hemodialysis (HD). A renal biopsy revealed an immune complex-mediated membranoproliferative glomerulonephritis (MPGN). Elevated thyroid hormones and suppressed TSH levels with elevated thyroperoxidase antibodies and thyroid stimulating immunoglobulins confirmed the diagnosis of Graves' disease. Corticosteroids were commenced and eventually thiamazole was added with gradual improvement of renal function, cessation of HD and discharge from the hospital. Conclusions Graves' disease complicated by MPGN is extremely rare, but can cause life-threatening complications.
2019Correlation between magnetic resonance imaging (MRI) findings and the new bone formation factor Dkk-1 in patients with spondyloarthritis.Clin RheumatolIn recent years, MRI has been regarded as a major diagnostic tool for spondyloarthritis (SpA), and anti-TNF therapy has been widely confirmed as an effective treatment strategy. This study was designed to investigate the correlation between the secreted protein dickkopf-1 (Dkk-1) and abnormal findings on magnetic resonance imaging (MRI) through a prospective study of 30 cases of SpA. Thirty patients with active SpA were included, all treated with recombinant human tumor necrosis factor (TNF) receptor-antibody fusion protein (YiSaiPu) injection at 50 mg/week for 6 months. All patients were also examined for their clinical, serological, and imaging manifestations of the condition before and after treatment. In patients receiving TNF inhibitor treatment, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and clinical activity indices BASDAI, BASFI, BASMI, ASDAS-CRP were significantly decreased (p < 0.01). Serum Dkk-1 concentration was also significantly decreased (p < 0.05), as were the scores of bone marrow edema of the sacroiliac joints and the spine (p < 0.05). The score of sacroiliac joint backfill was significantly increased (p < 0.05), and the baseline and changes in the serum Dkk-1 concentration were significantly correlated with the baseline and changes in spinal bone marrow edema levels. Inhibition of the level of serum Dkk-1 by TNF inhibitors may be the molecular basis for inhibiting the formation of new bone in SpA patients. In addition, spinal marrow edema may have significance for predicting new bone formation.
2018Levocetirizine Pretreatment Mitigates Lipopolysaccharide-Induced Lung Inflammation in Rats.Biomed Res IntThis research was conducted to investigate possible protective influences of levocetirizine, a nonsedating H antihistamine, against lipopolysaccharide (LPS)-induced lung injury in rats. Male Sprague Dawley rats received either levocetirizine (1 mg/kg/day, orally) or the vehicle of the drug (2 ml/kg/day, orally) for 1 week before a single IP injection of LPS (7.5 mg/kg). A group of normal rats served as control. The experiments were terminated 18 h after the LPS challenge. Serum C-reactive protein levels were determined. Moreover, total cell count, lactate dehydrogenase (LDH) activity, protein levels, and total NOx were evaluated in bronchoalveolar lavage fluid (BALF). Pulmonary edema was evaluated as the wet/dry lung weight ratio. Lung tissue homogenate was assessed for antioxidant/pro-oxidant status. BALF and lung tissue levels of tumor necrosis factor- (TNF-) were assessed. Lungs were examined for histological alterations. LPS-mediated lung injury was manifested by pulmonary edema, leukocyte infiltration, oxidative stress, and inflammation. Levocetirizine attenuated lung edema and mitigated the increases in BALF protein levels, LDH activity, and lung leukocyte recruitment in LPS-challenged rats. Additionally, TNF- protein levels in BALF and lung tissue were diminished by levocetirizine administration. Levocetirizine also exhibited a potent antioxidant activity as indicated by a decrease in lung tissue levels of malondialdehyde and an enhancement of superoxide dismutase activity. Histological examination of lung tissues confirmed the beneficial effect of levocetirizine against LPS-induced histopathological alterations. In conclusion, levocetirizine may offer protection against lung tissue damage and inflammation in LPS-challenged rats.
2018Characterization of Skeletal Muscle Strain Lesion Induced by Stretching in Rats: Effects of Laser Photobiomodulation.Photomed Laser SurgUnusual and exhaustive physical exercise can lead to muscle lesions depending on the type of contraction, intensity, duration, age, and level of conditioning. Different therapies have been proposed to prevent or reduce exercise-induced muscle damage.In this study, we investigate the effects of low-level laser therapy on skeletal muscle strain in an experimental model in rats.Male Wistar rats (200 g) were used. The animals were randomized into groups of six animals. We performed tibialis muscle elongation using a previously described protocol. The animals were anesthetized and submitted to passive stretching of the anterior tibial muscle attached to a weight corresponding to 150% of the body mass of the animal for 20 min, rested for 3 min, and received a second traction for 20 min. The cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10, edema, and C-reactive protein (CRP) levels were determined in the tibialis anterior muscle.Plasma extravasation of groups treated with different doses of laser energy, lesion +1 J (2.61 ± 0.46), lesion +3 J (2.33 ± 0.13), lesion +6 J (2.92 ± 0.91), and lesion +9 J (2.80 ± 0.55), shows a significant reduction of extravasation when compared with the injury group (5.46 ± 1.09). Laser therapy was able to significantly reduce CRP and cytokine levels (TNF-α, IL-1β, IL-6, and IL-10).Laser photobiomodulation reduced skeletal muscle edema as well as cytokines and CRP, leading to a significant reduction in inflammatory markers.
2018Effects of oat protein supplementation on skeletal muscle damage, inflammation and performance recovery following downhill running in untrained collegiate men.Food FunctThe positive influence of animal-based protein supplementation during muscle-damaging exercise has been widely studied. However, the effects of plant-based proteins remain unclear and require further clarification. This study investigated the protective role of oat protein against exercise induced muscle damage (EIMD), subsequent inflammation, and loss of performance induced by downhill running. Subjects consumed either oat protein (25 g protein) or a placebo for 14 days prior to a downhill running test and then for 4 days thereafter. Treatments with oat protein for 19 days markedly alleviated eccentric exercise induced skeletal muscle soreness, and reduced the elevation of plasma IL-6 concentrations and serum creatine kinase, myoglobin and C reactive protein contents. In addition, oat protein supplementation significantly inhibited limb edema following damaging exercise, and the adverse effects on muscle strength, knee-joint range of motion, and vertical jump performance were lessened. Furthermore, the administration of oat protein facilitated recovery from exhaustive downhill running in this study. These findings demonstrated that oat protein supplementation has the potential to alleviate the negative effects of eccentric exercise in untrained young males.
Assessment of factors affecting the spontaneous passage of lower ureteric calculus on the basis of lower ureteric calculus diameter, density, and plasma C- reactive protein level.Urol AnnThe study aimed to evaluate the factors which affect the spontaneous passage of lower ureteric calculus on the basis of noncontrast computed tomography kidneys, ureters, and bladder (NCCT KUB) stone diameter, stone density, and plasma C-reactive protein (CRP) level.We conducted a prospective study of 200 patients with lower ureteric calculus 5-10 mm in size, from October 2015 to December 2016. All patients underwent NCCT KUB region with a 5 mm axial and reformatted coronal section. Edema just above the calculus and rim sign at the level of calculus and density of calculus is evaluated. Only scan with isolated, unilateral, solitary ureteric calculus was included in the final analysis and monitored up to 4 weeks, and plasma CRP is estimated in all patients to determine the clinical outcome.A total of 200 patients (145 males, 55 females; mean age ± standard deviation, 34.73 ± 10.29) were included in the study. Lower ureteric calculus between 5-7 mm passed in 70% and 7-10 mm passed in 40%. There was 18% underestimation of maximum stone diameter in axial plane as compared to coronal plane. For spontaneous passage of calculus, craniocaudal (CC) diameter is more reliable then axial in NCCT. Rim sign and edema is absent in 64% of those passed spontaneous calculus. CRP level more than 2.45 mg/dl has low spontaneous expulsion rate. The stone with different HU passes through the ureter with same rate.Plasma CRP level and CC diameter and absence of rim sign on NCCT KUB are more reliable factors then density for spontaneous passage of ureteric calculus.
2018C-reactive protein may be useful to differentiate idiopathic orbital inflammation and orbital cellulitis in cases with acute eyelid erythema and edema.Clin OphthalmolIdiopathic orbital inflammation (IOI) and orbital cellulitis can present similar clinical features, and the diagnoses of these two disorders are sometimes confused. The purpose of the present study was to determine whether or not inflammatory markers in the blood can be useful to differentiate between IOI and orbital cellulitis in cases with acute eyelid erythema and edema.In this retrospective single-institute study, we reviewed the medical records spanning the past 10 years at the Department of Ophthalmology, Osaka Medical College Hospital, Takatsuki, Osaka, Japan, and found 45 cases, with patients >15 years of age, with presumed IOI. Their blood samples were obtained within 5 days after the onset of IOI. Of those cases, 15 patients (10 males, 5 females, mean age of 56.9 years; range 38-76 years) presented acute eyelid erythema and edema, and were initially misdiagnosed as orbital cellulitis. Thus, inflammatory markers in the blood (ie, white blood cells [WBCs] and C-reactive protein [CRP]) of those 15 patients were analyzed with 17 patients (10 males, 7 females) having orbital cellulitis. The receiver operating characteristic curve analysis was performed to determine the optimal cut-off values.The mean ± standard error (SE) levels of the WBC were 6.80±0.70×10/μL in the IOI patients, and 8.54±0.91×10/μL in the orbital cellulitis patients, and no significant differences were observed (=0.15, Student's -test). However, the mean ± SE levels of CRP were 1.04±0.43 mg/dL in the IOI patients, yet were significantly increased to 4.65±1.21 mg/dL in the orbital cellulitis patients (=0.01, Student's -test). The area under the curve value was 0.80 and the optimal cut-off value was 0.43 for orbital cellulitis, with sensitivity and specificity being 82% and 73%, respectively.The findings of this study indicate that CRP may be useful in distinguishing patients with idiopathic orbital inflammation from those with orbital cellulitis.
2019MRI findings for unilateral sternoclavicular arthritis: differentiation between infectious arthritis and spondyloarthritis.Skeletal RadiolTo analyze and identify magnetic resonance imaging (MRI) and clinical findings for the differentiation between infectious arthritis and spondyloarthritis in patients with unilateral sternoclavicular arthritis.We retrospectively collected and evaluated the magnetic resonance (MR) images of 21 patients diagnosed with unilateral sternoclavicular arthritis, including 12 with infection and nine with spondyloarthritis, between 2004 and 2017. Capsular distension, extracapsular fluid collection, periarticular muscle edema, the prevalence and distribution of bone marrow edema, and the prevalence and size of bone erosions were assessed on the MR images. Clinical data were also reviewed.Capsular distension was more prominent in patients with infectious arthritis than those with spondyloarthritis (p = 0.002); extracapsular fluid collection and periarticular muscle edema were also more common in infectious arthritis than spondyloarthritis (p < 0.001, respectively); moreover, bone erosions were larger in infectious arthritis than spondyloarthritis (p = 0.023). Other findings significantly associated with infectious arthritis included advanced age (p = 0.007), an elevated C-reactive protein (CRP) level (p = 0.001), and erythrocyte sedimentation rate (ESR) (p < 0.001). The prevalence and distribution of bone marrow edema and the prevalence of bone erosions on MRI, the white blood cell count, and sex showed no significant differences between the two groups.Capsular distension, extracapsular fluid collection, periarticular muscle edema, and the size of bone erosions on MRI, as well as the age, CRP level, and ESR of patients, could be helpful for differentiating infectious arthritis from spondyloarthritis involving the sternoclavicular joint.
2018Heart Failure After Ischemic Stroke or Transient Ischemic Attack in Insulin-Resistant Patients Without Diabetes Mellitus Treated With Pioglitazone.CirculationThe IRIS trial (Insulin Resistance Intervention After Stroke) demonstrated that pioglitazone reduced the risk for both cardiovascular events and diabetes mellitus in insulin-resistant patients. However, concern remains that pioglitazone may increase the risk for heart failure (HF) in susceptible individuals.In IRIS, patients with insulin resistance but without diabetes mellitus were randomized to pioglitazone or placebo (1:1) within 180 days of an ischemic stroke or transient ischemic attack and followed for ≤5 years. To identify patients at higher HF risk with pioglitazone, we performed a secondary analysis of IRIS participants without HF history at entry. HF episodes were adjudicated by an external review, and treatment effects were analyzed using time-to-event methods. A baseline HF risk score was constructed from a Cox model estimated using stepwise selection. Baseline patient features (individually and summarized in risk score) and postrandomization events were examined as possible modifiers of the effect of pioglitazone. Net cardiovascular benefit was estimated for the composite of stroke, myocardial infarction, and hospitalized HF.Among 3851 patients, the mean age was 63 years, and 65% were male. The 5-year HF risk did not differ by treatment (4.1% pioglitazone, 4.2% placebo). Risk for hospitalized HF was low and not significantly greater in pioglitazone compared with placebo groups (2.9% versus 2.3%, P=0.36). Older age, atrial fibrillation, hypertension, obesity, edema, high C-reactive protein, and smoking were risk factors for HF. However, the effect of pioglitazone did not differ across levels of baseline HF risk (hazard ratio [95% CI] for pioglitazone versus placebo for patients at low, moderate, and high risk: 1.03 [0.61-1.73], 1.10 [0.56-2.15], and 1.08 [0.58-2.01]; interaction P value=0.98). HF risk was increased in patients with versus those without incident myocardial infarction in both groups (pioglitazone: 31.4% versus 2.7%; placebo: 25.7% versus 2.4%; P<0.0001). Edema, dyspnea, and weight gain in the trial did not predict HF hospitalization but led to more study drug dose reduction with a lower mean dose of pioglitazone versus placebo (29±17 mg versus 33±15 mg, P<0.0001). Pioglitazone reduced the composite outcome of stroke, myocardial infarction, or hospitalized HF (hazard ratio, 0.78; P=0.007).In IRIS, with surveillance and dose adjustments, pioglitazone did not increase the risk of HF and conferred net cardiovascular benefit in patients with insulin resistance and cerebrovascular disease. The risk of HF with pioglitazone was not modified by baseline HF risk. The IRIS experience may be instructive for maximizing the net benefit of this therapy.URL: https://www.clinicaltrials.gov . Unique identifier: NCT00091949.
2018Serological inflammatory factors as biomarkers for anatomic response in diabetic macular edema treated with anti-VEGF.J Diabetes ComplicationsTo study the relationship between systemic pro-inflammatory factors and macular structural response to intravitreal bevacizumab for diabetic macular edema (DME).Prospective study including 30 cases with DME, treated with bevacizumab and a minimum follow-up of 6 months. All cases underwent baseline laboratory testing for cardiovascular risk (high sensitivity C-reactive protein (hsCRP), homocystein), dyslipidemia, renal dysfunction and glucose control. Serum levels of VEGF, soluble ICAM-1, MCP-1 and TNF-α were assessed by enzyme-linked immunosorbent assay kits. Significant associations between systemic factors and quantitative and qualitative spectral-domain optical coherence macular features were analyzed.A mean of 4.82 ± 0.56 intravitreal injections was performed, resulting in significant improvement of central foveal thickness (CFT) (p < 0.001). A significant association with third month CFT decrease <10% was found for hsCRP (3.33 ± 2.01 vs 1.39 ± 1.15 mg/l, p = 0.007) and ICAM1 (975.54 ± 265.49 vs 727.07 ± 336.09 pg/ml, p = 0.012). ROC curve analysis indicated hsCRP and ICAM1 as significant biomarkers for 3rd month reduced anatomic response (area under the curve (AUC) = 0.807, p = 0.009 for hsCRP; AUC = 0.788, p = 0.014 for ICAM1). ROC curve analysis revealed hsCRP as a significant biomarker for 6th month CFT decrease <10% (AUC = 0.903, p < 0.001, cutoff value = 1.81 mg/l). A significant association with 6th month CFT decrease ≥25% was found for serum MCP1 (244.69 ± 49.34 pg/ml vs 319.24 ± 94.88 pg/ml, p = 0.017) and serum VEGF (90.84 ± 37.33 vs 58.28 ± 25.19 pg/ml, p = 0.027). The combined model of serum VEGF and LDL-cholesterol was found to be predictive of 6th month hard exudate severity (p = 0.001, r2 = 0.463).Increased levels of hsCRP and ICAM1 were found to be significant biomarkers for early reduced anatomic response to anti-VEGF treatment. Cases with higher serum levels of such factors had increased CFT values, despite treatment, suggesting inner blood-retinal barrier breakdown that is not adequately responsive to anti-VEGF monotherapy.
2019Preinterventional hydrocortisone sustains the endothelial glycocalyx in cardiac surgery.Clin Hemorheol MicrocircPatients undergoing cardiac surgery commonly develop systemic inflammation associated with tissue edema, which impairs outcome. One main pathomechanism leading to the edema is the deterioration of the endothelial glycocalyx, a key component of the vascular barrier. In animal models hydrocortisone has proved to be protective for the glycocalyx.This trial evaluates the effect of hydrocortisone on glycocalyx integrity in patients undergoing cardiac surgery with cardiopulmonary bypass.In a prospective, randomized interventional pilot trial, 30 patients received either hydrocortisone (100 mg over 10 min) or placebo (saline control) before surgery. Plasma concentrations of glycocalyx constituents (syndecan-1, heparan sulfate) and various clinical parameters (respiratory and renal function, inflammatory markers, use of vasopressors, length of stay at the intensive care unit) were measured. Primary endpoint was a significant difference of glycocalyx constituents in plasma. Comparisons were made with Friedman's and Wilcoxon tests (paired data), or the Kruskal-Wallis and Mann-Whitney U tests (unpaired data). Holm-Bonferroni method was used for post-hoc corrections.Heparan sulfate and syndecan-1 increased significantly during and after cardiac surgery with cardiopulmonary bypass in both groups. Whereas the maximum increase of heparan sulfate was 12.3-fold in the control vs. 3.8-fold in the pretreated group (p < 0.05), syndecan-1 values showed no significant difference between the groups (maximal increase 3-fold). The inflammatory markers C-reactive protein and interleukin-6 were also higher in the control than in the hydrocortisone group, but there was no difference in patient mortality (zero), or in any clinical parameters.Pretreatment with hydrocortisone ameliorated shedding of heparan sulfate, a major constituent of the endothelial glycocalyx, in patients undergoing cardiac surgery with cardiopulmonary bypass, but had no relevant influence on various clinical parameters or patient mortality. The relatively small number of patients in this pilot study probably precluded detection of positive outcome differences.
2019Clinical Profile and Therapeutic Response of Scrub Typhus in Children: A Recent Trend from Eastern India.J Trop PediatrThe aim of this study was to assess the clinico-laboratory parameters, complications and therapeutic responses in children with scrub typhus in Eastern India.In this prospective, observational study, all children (age, <12 years) with suspected scrub typhus with a compatible clinical scenario were enrolled consecutively over six months. Cases confirmed by means of a positive IgM serology or a positive Weil-Felix reaction (OXK = 1/80 or above) were administered enteral doxycycline (4.5 mg/kg/day).Out of 94 recruited children, 61 had confirmed scrub typhus (mean age = 6.1 years, M:F = 1.1:1) with or without complications and having a considerably higher incidence of neurological presentation (meningoencephalistis n = 21, 34.4%). The most frequent manifestations included vomiting (n = 39, 63.9%), abdominal pain (n = 33, 54.1%), lymphadenopathy (n = 36, 59%), hepatosplenomegaly (n = 32, 52.5%), pedal edema (n = 32, 52.5%) and eschar formation (n = 30, 49.2%). Low hemoglobin levels, leukocytosis, thrombocytopenia, hypoalbuminemia, hyponatremia, increased liver enzymes and increased C-reactive protein were associated with delayed defervescence (>48 h).Scrub meningoencephalitis, with a notably higher incidence, showed favorable therapeutic response. Prompt and empiric doxycycline therapy could be lifesaving.
2018Pediatric post-streptococcal glomerulonephritis: Clinical and laboratory data.Pediatr IntAcute post-streptococcal glomerulonephritis (APSGN) is the most common post-infectious glomerulonephritis in childhood. The aim of this study was therefore to identify the possible risk factor(s) responsible for decreased glomerular filtration rate (GFR) in APSGN.The data of patients followed up with a diagnosis of APSGN in the Pediatric Nephrology Clinic of Gaziantep University Hospital between October 2014 and October 2016 were retrospectively evaluated.The total number of subjects was 75 (male/female, 42/33) with a mean age of 8.20 ± 3.25 years. The most common presentations were edema (86.7%), macroscopic hematuria (82.7%) and hypertension (73.3%, n = 55). On laboratory examination, 28 children (37.3%) had hypoalbuminemia, 58 (77.3%) had proteinuria, 20 (26.7%) had increased C-reactive protein (CRP), while 74 (98.7%) and 12 (16%) had decreased complement (C)3 and C4, respectively. The number of children with GFR <90 mL/min/1.73 m was 22 (29.3%). The risk of decreased GFR was significantly higher in patients with increased CRP (P = 0.001; OR, 3.58), hypoalbuminemia (P = 0.006; OR, 4.83), and decreased C4 (P = 0.010; OR, 11.53). Additionally, white blood cell (WBC) count, neutrophil count, and neutrophil/lymphocyte ratio (NLR) were significantly higher (P = 0.02, P = 0.006, P = 0.004, respectively) in patients with low GFR.Although the prognosis of APSGN in children is good, severe systemic complications and renal failure may develop during the follow-up period. Decreased C4, presence of hypoalbuminemia, and increased inflammatory markers (WBC, CRP, neutrophil count and NLR) might be possible risk factors for severity of renal involvement. Decreased C4, in particular, may be a risk factor for decreased GFR in those children.
2017Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome associated with cefotaxime and clindamycin use in a 6 year-old boy: a case report.Pan Afr Med JDrug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially life-threatening idiosyncratic drug reaction. It presents with extensive rash, fever, lymphadenopathy, hematologic abnormalities (eosinophilia and/or atypical lymphocytosis) and internal organ involvement. It has been described in association with more than 50 drugs. To the best of our knowledge neither cefotaxime nor clindamycin has been previously reported to induce DRESS syndrome in children. Clindamycin was reported only in adults as a cause of DRESS syndrome in the literature. In this report, we aimed to present a child with DRESS syndrome that developed after cefotaxime and clindamycin treatment. A 6-year-old boy was diagnosed with the left lower lobe pneumonia and pleural effusion. Parenteral cefotaxime and clindamycin were then started, after which the patient improved clinically and was discharged 7 days later with oral amoxicillin clavulanate treatment. After four days he was readmitted to the hospital with fever and cough. Chest X-ray revealed left lower lobe pneumonia and pleural effusion. We considered that the pneumonia was unresponsive to oral antibiotic treatment, and therefore parenteral cefotaxime and clindamycin were re-administered. As a result, his clinical and radiological findings were improved within 10 days. On the 12 of day of hospitalization, the body temperature has risen to 39°C, which we considered to be caused by antibiotics and stopped antibiotic treatment. At the same day he developed generalized maculopapular erythematous rash, which was considered an allergic reaction secondary to antibiotics. Despite the antihistaminic drug administration, the clinical status quickly deteriorated with generalized edema, lymphadenopathies and hepatosplenomegaly. Laboratory tests revealed a white blood cell count of 4300/μl, a lymphocyte count of 1300/μl, a hemoglobin level of 11.2 gr/dl, a platelet count of 120.000/μl, an eosinophilia ratio of 10% on peripheral blood smear, a C-reactive protein level of 20 mg/dl, a procalcitonin level of 23.94 ng/ml and an erythrocyte sedimentation rate of 48 mm/h. Anti nuclear antibody, anti-double stranded DNA, the serologic tests for Epstein Bar virus, herpes simplex virus, parvovirus, mycoplasma, toxoplasmosis, rubella, cytomegalovirus were all found negative. Bone marrow aspiration was consistent with an autoimmune reaction. An echocardiographic examination was normal. Thoracic tomography revealed multiple enlarged axillary, supraclavicular and anterior mediastinal lymph nodes. As the patient met 8 out of 9 RegiSCAR criteria for the diagnosis of DRESS, we started pulse methyl prednisolone (30 mg/kg/day) for three days followed by 2 mg/kg/day. On the 2nd day fever resolved and cutaneous rash and edema improved. Ten days after developing eruptions the patient was discharged. To our knowledge, we report the first pediatric case of DRESS syndrome following treatment with cefotaxime and clindamycin. Pediatricians should be aware of this potential complication associated with these commonly prescribed antibiotics.
2018Oxymatrine attenuates lipopolysaccharide-induced acute lung injury by activating the epithelial sodium channel and suppressing the JNK signaling pathway.Exp AnimThe epithelial sodium channel (ENaC) and mitogen-activated protein kinase (MAPK) pathway have been reported to be associated with the progression of acute lung injury (ALI). Oxymatrine (OMT) alone or combined with other drugs can ameliorate paraquat- or oleic acid-induced lung injury. However, the effect of OMT on lipopolysaccharide (LPS)-induced ALI remains unknown. The aim of the present study was to evaluate whether OMT can attenuate LPS-induced ALI through regulation of the ENaC and MAPK pathway using an ALI mouse model. Histological assessment of the lung and inflammatory cell counts in bronchoalveolar lavage fluid (BALF) were performed by H&E and Wright-Giemsa staining. The lung wet/dry (W/D) weight ratio and the levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), ENaC subunits, and the MAPK pathway members were determined. Isolated type II rat alveolar epithelial cells were incubated with OMT 30 min before LPS stimulation to investigate the activation of ENaC and the MAPK pathway. The results showed that OMT remarkably alleviated histopathologic changes in lung and pulmonary edema, reduced inflammatory cell counts in BALF, and decreased TNF-α and CRP levels in a dose-dependent manner. OMT significantly increased the three subunits of ENaC proteins in vivo and in vitro, while it decreased p-ERK/ERK, p-p38/p38, and p-JNK/JNK ratios in vivo. However, only the JNK pathway was markedly inhibited in vitro following pretreatment with OMT. Collectively, the results suggested that OMT might alleviate LPS-induced ALI by elevating ENaC proteins and inhibiting the JNK signaling pathway.
2018Central Sleep Apnea with Cheyne-Stokes Breathing in Heart Failure - From Research to Clinical Practice and Beyond.Adv Exp Med BiolCharacterized by periodic crescendo-decrescendo pattern of breathing alternating with central apneas, Central sleep apnea (CSA) with Cheyne-Stokes Breathing represents a highly prevalent, yet underdiagnosed comorbidity in chronic heart failure (CHF). A diverse body of evidence demonstrates increased morbidity and mortality in the presence of CSB. CSB has been described in both CHF patients with preserved and reduced ejection fraction, regardless of drug treatment. Risk factors for CSB are older age, male gender, high BMI, atrial fibrillation and hypocapnia.The pathophysiology of CSB has been explained by the loop gain theory, where a controller (the respiratory center) and a plant (the lungs) are operating in a reciprocal relationship (negative feedback) to regulate a key parameter (partial pressure of carbon dioxide (pCO)). The temporal interaction between these elements is dependent on the circulatory delay. Increased chemosensitivity/chemoresponsiveness of the respiratory center and/or augmented ascending non- CO stimuli from the C-fibers in the lungs (interstitial pulmonary edema), overly efficient ventilation when breathing at low volumes and prolonged circulation time are involved. An alternative hypothesis of CSB being an adaptive response of the failing heart has its merits as well. The clinical manifestation of CSB is usually poor, lacking striking symptoms and complaints. Witnessed apneas and snoring are infrequently reported by the sleep partner. Sometimes patients may report poor sleep quality with frequent awakenings, paroxysmal nocturnal dyspnea and frequent urination at night. Standard instrumental and laboratory studies, performed in CHF patients, may present clues to the presence of CSB. Concentric remodeling of the left ventricle and dilated left atrium (echocardiography), high BNP and C-reactive protein levels, increased ventilation-carbon dioxide output (VEVCO) and lower end-tidal CO (cardiopulmonary exercise testing), reduced diffusion capacity (pulmonary function testing) and hypocapnia (blood-gas analysis) may indicate the presence of CSB.CSB and cardiovascular disease are probably linked through bidirectional causality. Cyclic variations in heart rate, blood pressure, respiratory volume, partial pressure of arterial oxygen (pO) and pCO lead to sympathetic-adrenal activation. The latter worsens ventricular energetism and survival of cardiomyocytes and exerts antiarhythmogenic effects. It causes cardiac remodeling, potentiating the progression and the lethal outcome in CHF patients. Several treatment modalities have been proposed in CSB. The most commonly used are continuous positive airway pressure (CPAP), adaptive servoventilation (ASV) and nocturnal home oxygen therapy (HOT). Novel therapies like nocturnal supplemental CO and phrenic nerve stimulation are being tested recently. The current treatment recommendations (by the American Academy of Sleep Medicine) are for CPAP and HOT as standard therapies, while ASV is an option only in patients with EF > 45%. BPAP (bilevel device) remains an option only when there is no adequate response to previous modes of treatment. Acetazolamide and theophylline are options only after failing the above modalities and if accompanied by a close follow-up.
2017Sjögren's syndrome manifesting as clinicopathological features of TAFRO syndrome: A case report.Medicine (Baltimore)TAFRO syndrome is a newly proposed disorder that manifests as thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. In this report, we describe the development of severe TAFRO syndrome-like systemic symptoms during the clinical course of juvenile-onset Sjögren's syndrome in a 32-year-old woman.The patient was admitted due to dyspnea, fever, polyarthralgia, and generalized edema. She had been diagnosed with Sjögren's syndrome at the age of 14 years, based on histopathological examination of a biopsy of the minor salivary glands and the development of Raynaud's phenomenon, with no follow-up treatment required. On admission, she presented with anemia, elevated C-reactive protein levels, anasarca, and hepato-splenomegaly. A bone marrow examination revealed increased megakaryocytes with reticulin fibrosis, and the histopathology of an axillary lymph node was consistent with mixed-type Castleman disease. Eventually, she developed thrombocytopenia.Her symptoms fulfilled all of the major and minor categories of the diagnostic criteria for TAFRO syndrome. However, considering her prior diagnosis, we assumed that the clinical presentation was consistent with an acute exacerbation of Sjögren's syndrome. Unlike typical cases of TAFRO syndrome, the administration of relatively low-dose prednisolone relieved her symptoms.Differentiation between TAFRO syndrome and exacerbation of an autoimmune disease is clinically important, although this can be challenging. Identification of specific biomarkers for TAFRO syndrome would be clinically beneficial.
2018Phenotyping COPD exacerbations using imaging and blood-based biomarkers.Int J Chron Obstruct Pulmon DisAcute exacerbations of chronic obstructive pulmonary disease (AECOPD) are caused by a variety of different etiologic agents. Our aim was to phenotype COPD exacerbations using imaging (chest X-ray [CXR] and computed tomography [CT]) and to determine the possible role of the blood tests (C-reactive protein [CRP], the N-terminal prohormone brain natriuretic peptide [NT-proBNP]) as diagnostic biomarkers.Subjects who were hospitalized with a primary diagnosis of AECOPD and who had had CXRs, CT scans, and blood collection for CRP and NT-proBNP were assessed in this study. Radiologist blinded to the clinical and laboratory characteristics of the subjects interpreted their CXRs and CT images. ANOVA and Spearman's correlation were performed to test for associations between these imaging parameters and the blood-based biomarkers NT-proBNP and CRP; logistic regression models were used to assess the performance of these biomarkers in predicting the radiological parameters.A total of 309 subjects were examined for this study. Subjects had a mean age of 65.6±11.1 years, 66.7% of them were males, and 62.4% were current smokers, with a mean FEV 54.4%±21.5% of predicted. Blood NT-proBNP concentrations were associated with cardiac enlargement (area under the curve [AUC] =0.72, <0.001), pulmonary edema (AUC =0.63, =0.009), and pleural effusion on CXR (AUC =0.64, =0.01); whereas on CT images, NT-proBNP concentrations were associated with pleural effusion (AUC =0.71, =0.002). Serum CRP concentrations, on the other hand, were associated with consolidation on CT images (AUC =0.75, <0.001), ground glass opacities (AUC =0.64, =0.028), and pleural effusion (AUC =0.72, <0.001) on CT images. A serum CRP sensitivity-oriented cutoff point of 11.5 mg/L was selected for the presence of consolidation on CT images in subjects admitted as cases of AECOPD, which has a sensitivity of 91% and a specificity of 53% (<0.001).Elevated CRP may indicate the presence of pneumonia, while elevated NT-proBNP may indicate cardiac dysfunction. These readily available blood-based biomarkers may provide more accurate phenotyping of AECOPD and enable the discovery of more precise therapies.
2017[Risk factors and impacts on prognosis of ultrasound lung comets in patients undergoing hemodialysis].Zhonghua Yi Xue Za ZhiTo investigate the risk factors of ultrasound lung comets and its impact on the survivals of patients undergoing hemodialysis. One hundred and forty-two patients on hemodialysis (Male 76, female 66) were divided into three groups according to the score of lung comets (mild: ≤14 comets; moderate: 15 to 30 comets; severe: >30 comets). Seventy-two healthy subjects examined by lung ultrasound serve as a control. Pulmonary artery systolic pressure and left ventricular ejection fraction (LVEF) were assessed by Doppler ultrasonography. High-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor (TNF)-α were measured by the automatic analyzer and enzyme-linked immunosorbent assay. With the increasing age of the patients, lung comets scores increased (<0.05). There were significant differences in TNF-α (<0.05), interdialytic weight gain (IDWG) (<0.05), pulmonary artery systolic pressure and LVEF (<0.05) among three groups. In multivariate linear regression, the lung comets score was positively related to multiple clinical variables including New York Heart Association (NYHA) classification (=0.023), hsCRP (=0.042), TNF-α (<0.001), IDWG (=0.031), and pulmonary artery systolic pressure (<0.001). In the multivariate Cox proportional hazards models, lung comets score was independent risk factor for death (=0.001). In Kaplan-Meier survival analysis, the risk of all-cause mortality increased in parallel with lung comets score, and patients with lung comets score (>30 comets) were at highest risk of death among all three groups (log-rank test χ(2)=12.73, =0.001). Lung comets is associated with inflammation, pulmonary artery systolic pressure/volume overload and heart function. Lung comets score represents the alterations of heart function and it may serve as a powerful predictor of all-cause mortality for hemodialysis patients.
2018Anti-Osteoarthritic and Anti-Inflammatory Activities of Diazine: In Vitro and In Vivo Studies.Med Sci MonitBACKGROUND The present study evaluated the effects of diazine (DZN) on collagenase-induced osteoarthritis (OA) in rats. MATERIAL AND METHODS OA was produced via intra-articular injections of collagenase type II into the knee joint. The rats were then treated with DZN (25, 50, or 100 mg/kg, p.o.) for three weeks. At the end of the protocol, all rats were evaluated for paw latency, paw edema, and knee swelling. Additionally, serum concentrations of glycosaminoglycan (GAG), alkaline phosphatase (ALP), and C-reactive protein (CRP) were determined. X-rays were performed to estimate radiological and histopathological changes in the knee joint. The expressions of antioxidant enzymes, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were estimated in the synovial tissues. RESULTS DZN treatment attenuated inflammation in osteoarthritic rats, as evidenced by decreases in paw edema and knee swelling and enhanced paw latency compared to the negative control group. Additionally, there were significant decreases in the serum levels of CRP and GAG and increases in ALP in the DZN-treated groups compared to the negative control group. The radiological and histopathological results showed that DZN protected against cartilage damage in the knee joint. Additionally, MMP levels decreased and there were significant reductions in the expressions of antioxidant enzymes and TIPMs in the DZN-treated groups compared to the negative control group. CONCLUSIONS The present findings demonstrated the chondroprotective effects of DZN via its modulation of the expressions of TIMP-1 and MMPs in the synovial tissues of osteoarthritic rats.
2018Levels of Interleukin-1β, Interleukin-18, and Tumor Necrosis Factor-α in Cerebrospinal Fluid of Aneurysmal Subarachnoid Hemorrhage Patients May Be Predictors of Early Brain Injury and Clinical Prognosis.World NeurosurgAneurysmal subarachnoid hemorrhage (aSAH) is a severe cerebrovascular accident with high morbidity and mortality. The aim of this study is to investigate the relationship between level of inflammatory cytokines in cerebrospinal fluid (CSF) of aSAH patients, the severity of aSAH, and the outcome of aSAH patients.aSAH patients were prospectively included and followed-up for 6 months. CSF samples were collected at 1-3, 4-6, and 7-9 days after aSAH onset. Levels of interleukin (IL)-1β, IL-18, and tumor necrosis factor-α (TNF-α) in the CSF of aSAH patients were measured by enzyme-linked immunosorbent assay.Eighty-one aSAH patients were enrolled. The levels of IL-1β, IL-18 and TNF-α in the CSF were especially higher in the group of aSAH patients with cerebral edema, cerebral vasospasm, and a high grade on Hunt-Hess scale, the high World Federation of Neurological Surgeons grades, and Fisher grade (P < 0.01). Higher levels of plasma C-reactive protein in the blood were correlated with poor outcome. The areas under the receiver operating characteristic curves for the levels of inflammatory cytokines in CSF were 0.85, 0.84, and 0.95, respectively. Clinical features (age, Hunt-Hess grade, etc.) were positively correlated with poor outcomes (P < 0.05).The levels of IL-1β, IL-18, and TNF-α in CSF were elevated in aSAH patients and were positively associated with cerebral edema and acute hydrocephalus. Our findings suggest that CSF inflammatory cytokines might be biomarkers to assess severity and predict outcomes.
2017Combined treatment of diabetic nephropathy with alprostadil and calcium dobesilate.Exp Ther MedThis study investigated the effects of alprostadil combined with calcium dobesilate on the treatment of diabetic nephropathy. We recruited 80 patients with diabetic nephropathy, who were randomly divided into experimental (n=40) and control (n=40) groups. Patients received high-quality low-protein diabetic diet intervention and subcutaneous injection of insulin to adjust blood glucose, combined with antihypertensive, antiplatelet drugs, and other comprehensive treatments. The control group received alprostadil and the experimental group received alprostadil combined with calcium dobesilate. Both groups were treated for 12 weeks as one treatment cycle. The time to remission of clinical symptoms such as mental fatigue and weakness, limb edema, soreness and swelling of waist and knee, cold limbs and limb numbness and pain was significantly shorter in the experimental group than that in the control group (p<0.05). After intervention, the blood levels of small molecular weight proteins, such as β2-microglobulin (β2-MG), cystatin C (CysC), and retinol binding protein (RBP), were significantly lower in the experimental group than those in the control group (p<0.05). The levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) were significantly lower in the experimental group than those in the control group (p<0.05). The levels of 25-hydroxyvitamin D and parathyroid hormone were significantly higher in the experimental group than those in the control group (p<0.05). The level of angiotensin II was lower in the experimental group than that in the control group (p<0.05) and the level of fasting serum insulin was significantly higher in the experimental group than that in the control group (p<0.05). The homeostasis model assessment of insulin resistance (HOMA-IR) index was lower in the experimental group than that in the control group (p<0.05). The levels of renal function indexes, blood urea nitrogen, creatinine and uric acid, in experimental group were lower than those in control group (p<0.05). The levels of brain derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) were significantly higher in both groups after the intervention than those before the intervention (p<0.05). The levels of BDNF and IGF-1 were higher in the experimental group than that in control group after intervention (p<0.05). The application of alprostadil combined with calcium dobesilate in patients with diabetic nephropathy can effectively relieve clinical symptoms, improve renal functions, reduce blood levels small proteins, alleviate the inflammatory response, and regulate the levels of BDNF and IGF-1, thus improving the clinical treatment effect.
2018Effect of blood pressure on reversible posterior leukoencephalopathy syndrome in pre-eclampsia or eclampsia.Hypertens ResReversible posterior leukoencephalopathy syndrome (RPLS) is a critical maternal complication in some pre-eclampsia (PE) and nearly all eclampsia patients; RPLS is associated with high blood pressure (BP). However, the effect of BP on RPLS and the different characteristics of RPLS in PE or eclampsia are largely unknown. We consecutively collected data from 69 patients who were diagnosed with RPLS in PE or eclampsia between 2013 and 2017. The BP and biochemical indicators at onset and post onset of RPLS were examined to explore their likely correlation with RPLS. We grouped patients into PE (n=40) and eclampsia (n=29) groups according to whether a seizure had occurred. Information regarding BP, clinical symptoms and imaging features was collected retrospectively to explore the differences between groups. BP measurements (moderate and severe hypertension, systolic pressure (SBP), diastolic pressure (DBP) and mean arterial pressure (MAP) levels) and biochemical indicators (uric acid, lactate dehydrogenase (LDH), C-reactive protein and WBC) were higher at the onset of RPLS than post-onset of RPLS (P<0.001), whereas normal BP and serum albumin levels were lower (P<0.001). Moreover, the BP values (SBP, DBP and MAP) and LDH levels were significantly correlated with the degree of edema (Spearman's correlation, P<0.01). These results suggest that hypertension and LDH are likely factors in the development of RPLS in PE or eclampsia. Moreover, BP and LDH were closely related to the degree of brain edema, However, no significant differences were found between the PE and eclampsia groups with the exception of age and consciousness impairment.
2017Early Continuous Veno-Venous Hemofiltration Is Effective in Decreasing Intra-Abdominal Pressure and Serum Interleukin-8 Level in Severe Acute Pancreatitis Patients with Abdominal Compartment Syndrome.Blood PurifThe aim of this study was to evaluate the efficacy of early continuous veno-venous hemofiltration (CVVH) in decreasing the intra-abdominal pressure (IAP) and serum interleukin-8 (IL-8) level in severe acute pancreatitis (SAP) patients with abdominal compartment syndrome (ACS).Twenty-five ACS patients of SAP were enrolled in a prospective study conducted according to the standard management protocol. They were treated in the intensive care unit (ICU) of Affiliated Yidu Central Hospital of Weifang Medical College and underwent CVVH. Eleven patients were set up as the control group that received no hemofiltration and surgical treatment due to economic or other reasons but solely conventional treatment. Serum amylase, liver and kidney function, and C reactive protein were investigated before and after treatment. IAP and blood level of IL-8 were measured daily to investigate their time course of changes and the correlation between the 2 parameters.Serum amylase levels, C-reactive protein and IAP were significantly lower and liver and kidney function was significantly better than those of the control group (p < 0.05). IAP on admission to the ICU was high, at 22.9 ± 2.1 mm Hg. The IAP was significantly lower to 17.2 ± 2.2 mm Hg (p < 0.01) 24 h after the initiation of CVVH, and thereafter decreased rapidly. The average blood level of IL-8 was high at 88.2 ± 25.1 ng/L on admission. However, it significantly decreased to 63.2 ± 18.7 ng/L (p < 0.01) 24 h after the initiation of CVVH, and subsequently decreased. There was a significant positive correlation between the blood level of IL-8 and IAP(r = 0.62, p < 0.01).CVVH is effective to decrease the IAP and the blood level of IL-8 in ACS patients of SAP. The blood level of IL-8 was significantly correlated with IAP, suggesting that IL-8 might play an important role in the pathogenesis of ACS. Early CVVH appeared to be effective in the treatment of ACS in patients with SAP through the removal of causative cytokines such as IL-8, and it thereby decreased interstitial edema to lower IAP and should be applied in the early stage of ACS. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=480223.
2017Fever, rash, and leukopenia in a 32-year-old man · Dx?J Fam PractA 32-year-old man was admitted to our hospital with fever, chills, malaise, leukopenia, and a rash. About 3 weeks earlier, he'd had oral maxillofacial surgery and started a 10-day course of prophylactic amoxicillin/clavulanic acid. Fifteen days after the surgery, he developed a fever (temperature, 103° F), chills, arthralgia, myalgia, cough, diarrhea, and malaise. He was seen by his physician, who obtained a chest x-ray showing a lingular infiltrate. The physician diagnosed influenza and pneumonia in this patient, and prescribed oseltamivir, azithromycin, and an additional course of amoxicillin/clavulanic acid. Upon admission to the hospital, laboratory tests revealed a white blood cell count (WBC) of 3.1 k/mcL (normal: 3.2-10.8 k/mcL). The patient's physical examination was notable for lip edema, white mucous membrane plaques, submandibular and inguinal lymphadenopathy, and a morbilliform rash across his chest. Broad-spectrum antibiotics were initiated for presumed sepsis. On hospital day (HD) 1, tests revealed a WBC count of 1.8 k/mcL, an erythrocyte sedimentation rate of 53 mm/hr (normal: 20-30 mm/hr for women, 15-20 mm/hr for men), and a C-reactive protein level of 6.7 mg/dL (normal: <0.5 mg/dL). A repeat chest x-ray and orofacial computerized tomography scan were normal. By HD 3, all bacterial cultures were negative, but the patient was positive for human herpesvirus-6 on viral cultures. His leukopenia persisted and he had elevated levels of alanine transaminase ranging from 40 to 73 U/L (normal: 6-43 U/L) and aspartate aminotransferase ranging from 66 to 108 U/L (normal range: 10-40 U/L), both downtrending during his hospitalization. He also had elevated levels of antinuclear antibodies and anti-Smith antibody titers. A posterior-auricular biopsy was consistent with lymphocytic perivasculitis. The rash continued to progress, involving his chest, abdomen, and face. Bacterial and viral cultures remained negative and on HD 4, broad-spectrum antibiotics were discontinued.
2017The role of biomarkers in dilated cardiomyopathy: Assessment of clinical severity and reverse remodeling.Rev Port CardiolBiomarkers in dilated cardiomyopathy (DCM) reflect various pathobiological processes, including neurohormonal activation, oxidative stress, matrix remodeling, myocyte injury and myocyte stretch. We assessed the role of biomarkers in clinical and echocardiographic parameters and in left ventricular (LV) reverse remodeling (LVRR).In this prospective study of 50 DCM patients (28 men, aged 59±10 years) with LV ejection fraction (LVEF) <40%, LVRR was defined as an increase of >10 U in LVEF after optimal medical therapy.Baseline LVEF was 25.4±9.8% and LV end-diastolic diameter (LVEDD)/body surface area (BSA) was 34.2±4.5 mm/m. LVRR occurred in 34% of patients within 17.6±15.6 months. No correlation was found between B-type natriuretic peptide (BNP), 25-hydroxyvitamin D (25(OH)D), CA-125, high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a) [Lp(a)], noradrenaline, adrenaline, renin or aldosterone and LVRR. Patients in NYHA class III or IV, with pulmonary congestion or ankle edema, had higher CA-125, cystatin C, BNP and hs-CRP levels (p<0.05). CA-125 was correlated with BNP (r=0.61), hs-CRP (r=0.56) and uric acid (r=0.52) (all p=0.01). BNP correlated directly with LVEDD (r=0.49), LV volumes (r=0.51), pulmonary artery systolic pressure (PASP) (r=0.43) and E/e' (r=0.31), and was inversely correlated with LVEF (r=-0.50) and e' velocity (r=-0.32) (p<0.05). CA-125 was positively correlated with left atrial volume/BSA (r=0.46), E/A ratio (r=0.60) and PASP (r=0.49) (p<0.05).No correlation was found between biomarkers and LVRR, but CA-125, BNP and hs-CRP were predictors of clinical severity and congestion. BNP correlated with parameters of systolic and diastolic dysfunction, while CA-125 correlated with measures of diastolic dysfunction.
2018Increased serum C-reactive protein and decreased urinary aquaporin 2 levels are predictive of the efficacy of tolvaptan in patients with liver cirrhosis.Hepatol ResWater retention, hepatic ascites, and peripheral edema are significant problems in patients with liver cirrhosis (LC). Although furosemide and spironolactone are commonly used as treatment, they are often insufficient to treat hyponatremia and renal insufficiency in patients with LC. Tolvaptan (TVP) could provide an effective treatment alternative. However, predictive factors of a therapeutic response to TVP are unclear. Our aim was to examine clinical predictors of the response to TVP in patients with LC and water retention.Fifty-two patients were treated with TVP, with therapeutic effects judged by a decrease in body weight (≥2 kg) and increase in urinary volume (≥500 mL) within 7 days. Blood biochemical tests were carried out at baseline and post-treatment, including serum soluble CD14 (sCD14) and urinary aquaporin 2 (AQP2) levels. Clinical and laboratory predictive factors of a TVP response were evaluated by univariate and multivariate analyses.The overall response to TVP was 55.8%. On univariate analyses, serum C-reactive protein (CRP) level, the neutrophil-to-lymphocyte ratio, urinary blood urea nitrogen, and urinary AQP2 were predictors of the TVP response, with only serum CRP retained on multivariate analysis. A higher serum sCD14 level was strongly associated with a non-response to TVP. A decrease in urinary AQP2 to undetectable level was associated with a response.Tolvaptan provides a rapid and strong effect to improve water retention in patients with LC. Baseline serum sCD14 and CRP levels are useful predictors of a response to TVP, with a decrease in urinary AQP2 during treatment indicating an early response.
2017Importance of Clinical and Laboratory Findings in the Diagnosis and Surgical Prognosis of Patients with Constrictive Pericarditis.Arq Bras CardiolInternational studies have reported the value of the clinical profile and laboratory findings in the diagnosis of constrictive pericarditis. However, Brazilian population data are scarce.To assess the clinical characteristics, sensitivity of imaging tests and factors related to the death of patients with constrictive pericarditis undergoing pericardiectomy.Patients with constrictive pericarditis surgically confirmed were retrospectively assessed regarding their clinical and laboratory variables. Two methods were used: transthoracic echocardiography and cardiac magnetic resonance imaging. Mortality predictors were determined by use of univariate analysis with Cox proportional hazards model and hazard ratio. All tests were two-tailed, and an alpha error ≤ 5% was considered statically significant.We studied 84 patients (mean age, 44 ± 17.9 years; 67% male). Signs and symptoms of predominantly right heart failure were present with jugular venous distention, edema and ascites in 89%, 89% and 62% of the cases, respectively. Idiopathic etiology was present in 69.1%, followed by tuberculosis (21%). Despite the advanced heart failure degree, low BNP levels (median, 157 pg/mL) were found. The diagnostic sensitivities for constriction of echocardiography and magnetic resonance imaging were 53.6% and 95.9%, respectively. There were 9 deaths (10.7%), and the risk factors were: anemia, BNP and C reactive protein levels, pulmonary hypertension >55 mm Hg, and atrial fibrillation.Magnetic resonance imaging had better diagnostic sensitivity. Clinical, laboratory and imaging markers were associated with death.
2017Hemorrhage enhances cytokine, complement component 3, and caspase-3, and regulates microRNAs associated with intestinal damage after whole-body gamma-irradiation in combined injury.PLoS OneHemorrhage following whole-body γ-irradiation in a combined injury (CI) model increases mortality compared to whole-body γ-irradiation alone (RI). The decreased survival in CI is accompanied by increased bone marrow injury, decreased hematocrit, and alterations of miRNA in the kidney. In this study, our aim was to examine cytokine homeostasis, susceptibility to systemic bacterial infection, and intestinal injury. More specifically, we evaluated the interleukin-6 (IL-6)-induced stress proteins including C-reactive protein (CRP), complement 3 (C3), Flt-3 ligand, and corticosterone. CD2F1 male mice received 8.75 Gy 60Co gamma photons (0.6 Gy/min, bilateral) which was followed by a hemorrhage of 20% of the blood volume. In serum, RI caused an increase of IL-1, IL-2, IL-3, IL-5, IL-6, IL-12, IL-13, IL-15, IL-17A, IL-18, G-CSF, CM-CSF, eotaxin, IFN-γ, MCP-1, MIP, RANTES, and TNF-α, which were all increased by hemorrhage alone, except IL-9, IL-17A, and MCP-1. Nevertheless, CI further elevated RI-induced increases of these cytokines except for G-CSF, IFN- γ and RANTES in serum. In the ileum, hemorrhage in the CI model significantly enhanced RI-induced IL-1β, IL-3, IL-6, IL-10, IL-12p70, IL-13, IL-18, and TNF-α concentrations. In addition, Proteus mirabilis Gram(-) was found in only 1 of 6 surviving RI mice on Day 15, whereas Streptococcus sanguinis Gram(+) and Sphingomonas paucimobilis Gram(-) were detected in 2 of 3 surviving CI mice (with 3 CI mice diseased due to inflammation and infection before day 15) at the same time point. Hemorrhage in the CI model enhanced the RI-induced increases in C3 and decreases in CRP concentrations. However, hemorrhage alone did not alter the basal levels, but hemorrhage in the CI model displayed similar increases in Flt-3 ligand levels as RI did. Hemorrhage alone altered the basal levels of corticosterone early after injury, which then returned to the baseline, but in RI mice and CI mice the increased corticosterone concentration remained elevated throughout the 15 day study. CI increased 8 miRNAs and decreased 10 miRNAs in serum, and increased 16 miRNA and decreased 6 miRNAs in ileum tissue. Among the altered miRNAs, CI increased miR-34 in the serum and ileum which targeted an increased phosphorylation of ERK, p38, and increased NF-κB, thereby leading to increased iNOS expression and activation of caspase-3 in the ileum. Further, let-7g/miR-98 targeted the increased phosphorylation of STAT3 in the ileum, which is known to bind to the iNOS gene. These changes may correlate with cell death in the ileum of CI mice. The histopathology displayed blunted villi and villus edema in RI and CI mice. Based on the in silico analysis, miR-15, miR-99, and miR-100 were predicted to regulate IL-6 and TNF. These results suggest that CI-induced alterations of cytokines/chemokines, CRP, and C3 cause a homeostatic imbalance and may contribute to the pathophysiology of the gastrointestinal injury. Inhibitory intervention in these responses may prove therapeutic for CI and improve recovery of the ileal morphologic damage.
2017Assessment of histopathological features of maculopapular viral exanthem and drug-induced exanthem.J Cutan PatholViral infections and drug reactions are the commonest causes of exanthems in clinical practice. Clinically, their overlapping features may pose a diagnostic challenge. Hematologic, in vitro, and drug provocation tests are either unreliable or impractical.This was a descriptive, prospective study to assess and compare histopathological features of maculopapular viral and drug exanthem. Subjects fulfilling case definition of exanthems were included. Serum C-reactive protein (CRP) and absolute eosinophil count (AEC) were also studied.Skin biopsy slides of 48 cases were evaluated and AEC and CRP were performed. Both median AEC and CRP were lower in viral exanthem compared with drug exanthem. On histopathological evaluation, features such as lymphocytic exocytosis, and dermal infiltrate of eosinophils, lymphocytes and histiocytes were seen in a significantly greater number of drug exanthems. Other findings such as focal spongiosis, acanthosis, keratinocyte necrosis, basal cell damage, papillary dermal edema and atypical lymphocytes in the dermis were also observed in higher though not statistically significant number of drug exanthem biopsies.Certain histopathological features can help to differentiate between the two exanthems and this modality may be used in situations when there is clinical overlap and when drug rechallenge cannot be undertaken.
2017[Clinical analysis of 34 cases with sepsis and systemic capillary leak syndrome].Zhonghua Wai Ke Za ZhiTo study the clinical characteristics of sepsis with systemic capillary leak syndrome(SCLS) and to evaluate the therapeutic effect and clinical significance of fluid therapy adjusted timely in these patients. The clinical data of 34 patients with sepsis and SCLS in the Department of Hepatobiliary Surgery ICU of General Hospital of People's Liberation Army General Hospital from July 2014 to January 2016 were retrospectively analyzed.There were 21 males and 13 females, aged from 21 to 74 years, with an average age of 56.3 years.Primary disease as follows: 18 cases with severe acute pancreatitis, 7 postoperative cases of subtotal hepatectomy, 5 postoperative cases of pancreatoduodenectomy, 4 postoperative cases of cholelithiasis.These patients were divided into survival group and death group according to their 28-day survival status.The clinical data including C-reactive protein(CRP), platelets (PLT), brain natriuretic peptide (BNP), the level of arterial blood lactic acid(LAC), oxygenation index(PaO/FiO, OI), net fluid balance(NFB) and norepinephrine dosage(NE) were collected and compared between two groups at three different intervals(day 1-3, day 4-6, day 7-9). The measurement data and numeration data were statistically analyzed with test and χ test respectively to explore the inherent characteristics of the disease evolution and its clinical significance. The survival group (=23)and the death group(=11)had no significant difference in the characteristics of basic clinical characters.The condition of the survival group and the death group were both in progress in 1-3 days period manifested as increased CRP(=-0.473, =0.640) and BNP levels(=0.140, =0.895), decreased PLT counts(=-0.505, =0.620) in the inflammatory response, decreased LAC(=-1.008, =0.320) and OI level (=-2.379, =0.020)in tissue perfusion index, and positive fluid balance(NFB: =0.910, =0.370), required NE(=-0.853, =0.400) to maintain effective perfusion pressure with systemic edema in both groups.There was no significant difference of all these clinical parameters between the two groups.The patients' condition of the survival group reached a plateau phase, whereas all relative indicators of the death group implied significant aggravation and deterioration of systemic infection(CRP: =-3.438, =0.000; PLT: =1.649, =0.110; BNP: =-10.612, =0.000), tissue perfusion (LAC: =-11.305, =0.000; OI: =2.743, =0.010)and tissue edema NFB(=-4.257, =0.000) and NE(=-7.956, =0.000) in 4-6 days period.In the last 7-9 days period the patients' condition of the survival group took a turn for improvement, yet the condition of the death group continued to deteriorate, refractory septic shock developed and multiple organ dysfunction syndrome followed afterwards inevitably(CRP: =-10.036, =0.000; PLT: =6.061, =0.000; BNP: =-10.119, =0.000; LAC: =-24.466, =0.000; OI: =13.443, =0.010; NFB: =-8.345, =0.000; NE: =-7.121, =0.000). The condition of patient with sepsis and SCLS would be improved markedly at the critical turning point around 7-9 days period since the effective systemic treatment began.If the infection does not be significantly constrolled and SCLS still remains in a sustained extravasation period in 7-9 days, the prognosis of these patients may be worse and the mortality may be higher than that of the patients mentioned before.
2017Anti-exudation effects of sodium ferulate and oxymatrine combination via modulation of aquaporin 1.Exp Ther MedThe present study aimed to investigate the anti-exudative effects of sodium ferulate combined with oxymatrine in a mouse model of acetic acid-induced peritonitis. Furthermore, the underlying mechanisms were explored by determining the effects of these drugs on the volume and aquaporin 1 (AQP1) expression in vascular endothelial cells on omentum majus and human umbilical vein endothelial cells (HUVEC). Treatment with sodium ferulate combined with oxymatrine was shown to significantly inhibit acetic acid-induced vascular permeability in the peritonitis model mice and furthermore to significantly decrease the optical density of Evans blue, the leukocyte number and the levels of interleukin-6, C-reactive protein and interferon-γ in peritoneal lavage fluid. Pathological analysis of the omentum majus revealed that sodium ferulate and oxymatrine combination treatment significantly alleviated vascular endothelial cell edema and capillary loss. , flow cytometry revealed that the volume of HUVECs was significantly reduced in the drug treatment groups, as reflected in the forward scatter value. The optical density of AQP1 on the membrane of the vascular endothelial cells on omentum majus and HUVECs were significantly increased in the drug treatment groups compared with the model group. These results indicated that sodium ferulate and oxymatrine combination treatment possessed prominent anti-exudative effects and that the underlying mechanisms are likely to include the improvement of vascular endothelial cellular edema, possibly by upregulation of AQP1 expression on their membrane, which requires further exploration.
2017Concentration of acute phase factors in vitreous fluid in diabetic macular edema.Jpn J OphthalmolDiabetic retinal maculopathy is associated with acute and chronic local inflammation. We measured the concentrations of acute phase factors in vitreous fluid of patients with diabetic macular edema (DME) and examined their relations to visual acuity and central retinal thickness (CRT) both before and after vitrectomy.Retrospective.Vitreous fluid was collected during vitreoretinal surgery from 19 patients with DME and 12 control subjects with epiretinal membrane. The concentrations of acute phase factors (α2-macroglobulin, haptoglobin, C-reactive protein, serum amyloid P and A, procalcitonin, ferritin, tissue plasminogen activator, fibrinogen) and vascular endothelial growth factor (VEGF) were measured with multiplex assays. CRT of macular edema was measured by optical coherence tomography (OCT).The levels of serum amyloid P, procalcitonin, ferritin, and fibrinogen in vitreous fluid were increased in DME patients compared with control subjects. The levels of procalcitonin and fibrinogen in DME patients were inversely correlated with visual acuity both before and 3 months after vitrectomy but not 6 months postsurgery. The concentrations of these four factors were not correlated with either CRT or the vitreous levels of VEGF in DME patients.Acute phase factors may contribute to local inflammation in DME and may therefore influence disease progression.
2017Crescentic glomerular nephritis associated with rheumatoid arthritis: a case report.J Med Case RepRheumatoid arthritis is a systemic disorder where clinically significant renal involvement is relatively common. However, crescentic glomerular nephritis is a rarely described entity among the rheumatoid nephropathies. We report a case of a patient with rheumatoid arthritis presenting with antineutrophil cytoplasmic antibody-negative crescentic glomerular nephritis.A 54-year-old Sri Lankan woman who had recently been diagnosed with rheumatoid arthritis was being treated with methotrexate 10 mg weekly and infrequent nonsteroidal anti-inflammatory drugs. She presented to our hospital with worsening generalized body swelling and oliguria of 1 month's duration. Her physical examination revealed that she had bilateral pitting leg edema and periorbital edema. She was not pale or icteric. She had evidence of mild synovitis of the small joints of the hand bilaterally with no deformities. No evidence of systemic vasculitis was seen. Her blood pressure was 170/100 mmHg, and her jugular venous pressure was elevated to 7 cm with an undisplaced cardiac apex. Her urine full report revealed 2+ proteinuria with active sediment (dysmorphic red blood cells [17%] and granular casts). Her 24-hour urinary protein excretion was 2 g. Her serum creatinine level was 388 μmol/L. Abdominal ultrasound revealed normal-sized kidneys with acute parenchymal changes and mild ascites. Her renal biopsy showed renal parenchyma containing 20 glomeruli showing diffuse proliferative glomerular nephritis, with 14 of 20 glomeruli showing cellular crescents, and the result of Congo red staining was negative. Her rheumatoid factor was positive with a high titer (120 IU/ml), but results for antinuclear antibody, double-stranded deoxyribonucleic acid, and antineutrophil cytoplasmic antibody (perinuclear and cytoplasmic) were negative. Antistreptolysin O titer <200 U/ml and cryoglobulins were not detected. The results of her hepatitis serology, retroviral screening, and malignancy screening were negative. Her erythrocyte sedimentation rate was 110 mm in the first hour, and her C-reactive protein level was 45 mg/dl. Her liver profile showed hypoalbuminemia of 28 g/dl. She was treated with immunomodulators and had a good recovery of her renal function.This case illustrates a rare presentation of antineutrophil cytoplasmic antibody-negative crescentic glomerular nephritis in a patient with rheumatoid arthritis, awareness of which would facilitate early appropriate investigations and treatment.
2016A case of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome complicated by IgA nephropathy with nephrotic syndrome.CEN Case RepA 62-year-old man visited our hospital with a mild sore throat, high-grade fever, and clavicular pain. Seven years earlier, he had been diagnosed with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. His clavicles were tender and remarkably swollen. Also noted was marked pitting edema in the lower extremities and pustulosis on the palms and soles of the feet. Laboratory studies on admission showed an elevated white cell count (23,400/μl) and serum C-reactive protein level (24.4 mg/dl). Urinalysis revealed proteinuria (2+) and occult blood (3+) with numerous dysmorphic red blood cells and hyalin casts. The patient was diagnosed with recurrence of his SAPHO syndrome and started on oral glucocorticoid therapy. By day 9 after admission, he had gained 16 kg in body weight, and his proteinuria (6.4 g/day) and serum creatinine level (2.3 mg/dl) were elevated. Renal biopsy revealed mesangial proliferative glomerulonephritis with deposition of IgA and C3 in the mesangial area and along the capillary walls. The patient was diagnosed with IgA nephropathy accompanied by nephrotic syndrome. With oral prednisolone therapy, his fever, clavicular pain, and proteinuria were gradually relieved. The clinical course in this case suggests the onset of nephrotic syndrome with IgA nephropathy was associated with the recurrence of the patient's SAPHO. To our knowledge, this is the first reported case of SAPHO-associated IgA nephropathy.
2017Adult acute supraglottitis: Analysis of 358 patients for predictors of airway intervention.LaryngoscopeAcute supraglottitis is a potentially life-threatening condition due to rapid onset upper airway obstruction. The study aimed to characterize adult acute supraglottitis patients and to recognize factors associated with an aggressive disease course.Retrospective chart review.All adult acute supraglottitis patients admitted to a single academic medical center between 2000 and 2014 were included and their medical charts reviewed. The main outcome measures were airway intervention and mortality.Three hundred fifty-eight patients were enrolled. Mean age was 53 years (range, 16-92 years), with 62.8% males. Sore throat (79%) and dysphagia (70.9%) were the most common symptoms. Stridor (3.6%), tachypnea (5.7%), and dyspnea (6.4%) were uncommon but significantly associated with airway intervention. The epiglottis was most commonly involved (67%). Involvement of the epiglottis and aryepiglottic folds showed a trend of correlation to airway intervention. Blood glucose levels, C-reactive protein (CRP) levels, and relative neutrophilia were significantly higher in patients admitted to the intensive care unit or requiring airway intervention. Thirty-four patients (9.5%) required intensive care unit admission. Sixteen patients (4.4%) required airway intervention. Recurrent episodes of supraglottitis, seen in 19 patients, were more common in males (P = .048), and tended to have a more severe clinical course, requiring more airway interventions (P = .005) and intensive care unit admissions (P = .016).The typical high risk patient-a male, with dyspnea and stridor, presenting with edema of the epiglottis and aryepiglottic folds, elevated CRP, hyperglycemia, and a history of recurrent episodes-should warrant more aggressive treatment and closer observation.4 Laryngoscope, 127:2106-2112, 2017.
2017[Marcato aumento delle concentrazioni di procalcitonina dopo idroclorotiazide-edema polmonare indotta.]Recenti Prog MedIn the Medline database there are approximately 60 cases reporting toxic pulmonary edema, a life-threatening event, induced after consumption of hydrochlorothiazide, one of the most common antihypertensive drugs. Moreover, increased procalcitonin concentrations have been reported after cardiogenic pulmonary edema. We report the rare case of a hydrochlorothiazide-induced pulmonary edema, which was followed by a marked increase of the procalcitonin concentrations.A middle-aged woman was admitted to the Emergency Department for severe dyspnea and chills. Such symptoms began 30 minutes after consumption of hydrochlorothiazide. Her physical examination and chest-X-ray were compatible with pulmonary edema, however her brain natriuretic peptide levels and echocardiogram were almost normal. Interestingly she had extremely elevated procalcitonin concentrations with normal white blood cells count and C-reactive protein levels only mildly increased. We hypothesized toxic pulmonary edema and started treatment with non-invasive mechanical ventilation, with the patient presenting rapid clinical improvement.Even if extremely rare, hydrochlorothiazide may induce pulmonary edema; significant increase of procalcitonin concentrations may occur in this condition and perhaps in other cases of toxic pulmonary edema. Practitioners should be aware of this condition in order to spare expensive and useless, in this case, investigations such as blood cultures and treatments (antibiotics) if other signs of infection are absent.
2017Tanshinone inhibits neuronal cell apoptosis and inflammatory response in cerebral infarction rat model.Int J Immunopathol PharmacolWe aimed to investigate the effect and mechanisms of tanshinone (TSN) IIA in cerebral infarction. The cerebral infarction rat model was established by middle cerebral artery occlusion (MCAO). After pretreatment with TSN, cerebral infarct volume, cerebral edema, and neurological deficits score were evaluated, as well as cell apoptosis in hippocampus and cortex of the brain was examined with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were determined by Enzyme-Linked Immunosorbent Assay (ELISA). In addition, rat primary neuronal cells were isolated and cultured in oxygen-glucose deprivation (OGD) conditions. After pretreatment with TSN, cell viability and apoptosis were observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. The expressions of Bax and B-cell lymphoma 2 (Bcl-2) were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. Compared with untreated cerebral infarction rat, TSN treatment significantly reduced cerebral infarct volume, cerebral edema, and neurological deficits score ( P < 0.05). Cell apoptosis as well as the levels of IL-6, TNF-α, and CRP in hippocampus and cortex of cerebral infarction rat were inhibited after pretreatment with TSN ( P < 0.05). Furthermore, TSN remarkably increased cell viability and inhibited cell apoptosis ratio ( P < 0.05) in OGD-induced rat neuronal cells. Besides, TSN significantly downregulated the expression of Bax and upregulated Bcl-2 ( P < 0.05). TSN IIA has a preventive effect on cerebral infarction by inhibiting neuronal cell apoptosis and inflammatory response in vitro and in vivo.
2017A Rare Clinical Entity: Staphylococcus-Related Glomerulonephritis.Exp Clin TransplantStaphylococcus aureus is a rare cause of postinfectious glomerulonephritis, and Staphylococcus-related glomerulonephritis primarily occurs in middle-aged or elderly patients. Patients with Staphylococcus-related glomerulonephritis also present with hematuria, proteinuria of varying degrees, rising serum creatinine levels, and/or edema. The severity of renal insufficiency is proportional to the degree of proliferation and crescent formation. Here, we present a diabetic patient admitted with a history of 1 week of left elbow pain. Laboratory results revealed that erythrocyte sedimentation rate was 110 mm/hour, serum creatinine level was 1 mg/dL, C-reactive protein level was 150 mg/L, and magnetic resonance imaging showed signal changes in favor of osteomyelitis at the olecranon level, with diffuse edematous appearance in the elbow skin tissue and increased intra-articular effusion. After diagnosis of osteomyelitis, ampicillin/sulbactam and teicoplanin were administered. After day 7 of admission, the patient developed acute kidney injury requiring hemodialysis under antibiotic treatment. Kidney biopsy was performed to determine the underlying cause, which showed Staphylococcus-related glomerulonephritis. Recovery of renal functions was observed after antibiotic and supportive treatment.
2017Sarcopenia and sarcopenic obesity in comparison: prevalence, metabolic profile, and key differences. A cross-sectional study in Italian hospitalized elderly.Aging Clin Exp ResThe aim of this study is to identify the prevalence, assess the metabolic profile, and key differences (versus healthy) in a cohort of subjects with sarcopenia (S) and in sarcopenic obesity (SO) hospitalized elderly.A standardized comprehensive geriatric assessment was performed. We enrolled 639 elderly subjects (196 men, 443 women) with a mean age of 80.90 ± 7.77 years. Analysis of variance and a multinomial logistic regression analysis adjusting for covariates were used to assess the differences between groups.The prevalence of (S) was 12.42% in women and 23.47% in men. (SO) was 8.13% in women and 22.45% in men. Data showed that either groups had a functional impairment (Barthel index < 50 points). (S) had the mean value of erythrocyte sedimentation rate (ESR) (>15 mm/h), CPR (>0.50 mg/dl) homocysteine (>12 micromol/l), and hemoglobin (<12 g/dl). Ferritin level over the range (>145 mcg/dl) was detected in either cohort (due to inflammation). (SO) had glycemia (>110 mg/dl). Key differences in (S) cohort (versus healthy) were a reduction in functional impairment (p < 0.001), an increase in white blood cell (p < 0.01), a decrease in iron level (p < 0.05), in electrolytes balance (Na: p < 0.01 and Cl: p < 0.01), and tyroid function (TSH: p < 0.001). In addition, (S) had higher state of inflammation (erythrocyte sedimentation rate: p < 0.05 and C-reactive protein: p < 0.01), and an increase of risk of fractures (FRAX: OR 1.07; p < 0.001), risk of malnutrition (mini nutritional assessment: p < 0.001), and risk of edema (extra cellular water: p < 0.001). In (SO) cohort, an increase in white blood cell (p < 0.001) and erythrocyte sedimentation rate (p < 0.05) was observed.(S) subjects appears more vulnerable than (SO). Sarcopenia is closely linked to an increase in the risk of hip-femur fractures, inflammation, edema, and malnutrition. The (SO) subjects seem to benefit from the "obesity paradox."
2017Intravenous Dexamethasone Administration Before Orthognathic Surgery Reduces the Postoperative Edema of the Masseter Muscle: A Randomized Controlled Trial.J Oral Maxillofac SurgDexamethasone seems to suppress postoperative swelling. However, the standard administration dose of dexamethasone for bilateral sagittal split osteotomy (BSSO) has not been reported. This study focused on clarifying the most effective dose of dexamethasone for BSSO.This research was planned as a prospective, randomized controlled, double-blind study. Patients undergoing BSSO were randomly assigned to receive intravenous preoperative dexamethasone under 3 different dose conditions: 16 mg, 8 mg, and 0 mg (control). The endpoints of this study were 1) postoperative changes in masseter muscle thickness and buccal soft tissue thickness; 2) postoperative changes in maximum incisal opening; 3) postoperative changes in sensation of the chin and lower lip region; 4) postoperative changes in blood examination findings (white blood cell count, neutrophil count, C-reactive protein level, and lymphocyte count); and 5) types of complications. Data were recorded at 2 to 4 time intervals: before surgery, postoperative day 1, postoperative day 2, and postoperative day 3. Average age, gender, average body mass index, average surgery time, and average blood loss also were examined. Data were analyzed by 1-way analysis of variance (Bonferroni multiple-comparisons test) after the Bartlett test.We enrolled 24 patients, including 5 men and 19 women, in this study. The rate of increase in the thickness of the masseter muscle 24 hours after BSSO was 38.4% in the 16-mg group (n = 8), 57.7% in the 8-mg group (n = 8), and 56.1% in the 0-mg group (n = 8). The rate of increase in masseter muscle thickness in the 16-mg group was significantly lower than that in the 0-mg group (P < .05). Regarding the number of lymphocytes after surgery, the 16-mg and 8-mg groups maintained preoperative levels whereas there was a reduced number of lymphocytes in the control group. No statistically significant results were obtained for the following study endpoints: postoperative changes in maximum incisal opening and postoperative changes in sensation of the chin and lower lip region.This investigation showed that the most effective dose of dexamethasone for BSSO is 16 mg.
2016Extreme Mountain Ultra-Marathon Leads to Acute but Transient Increase in Cerebral Water Diffusivity and Plasma Biomarkers Levels Changes.Front PhysiolPioneer studies demonstrate the impact of extreme sport load on the human brain, leading to threatening conditions for athlete's health such as cerebral edema. The investigation of brain water diffusivity, allowing the measurement of the intercellular water and the assessment of cerebral edema, can give a great contribution to the investigation of the effects of extreme sports on the brain. We therefore assessed the effect of supra-physiological effort (extreme distance and elevation changes) in mountain ultra-marathons (MUMs) athletes combining for the first time brain magnetic resonance imaging (MRI) and blood parameters. This longitudinal study included 19 volunteers (44.2 ± 9.5 years) finishing a MUM (330 km, elevation + 24000 m). Quantitative measurements of brain diffusion-weighted images (DWI) were performed at 3 time-points: Before the race, upon arrival and after 48 h. Multiple blood biomarkers were simultaneously investigated. Data analyses included brain apparent diffusion coefficient (ADC) and physiological data comparisons between three time-points. The whole brain ADC significantly increased from baseline to arrival ( = 0.005) and then significantly decreased at recovery ( = 0.005) to lower values than at baseline ( = 0.005). While sodium, potassium, calcium, and chloride as well as hematocrit (HCT) changed over time, the serum osmolality remained constant. Significant correlations were found between whole brain ADC changes and osmolality ( = 0.01), cholesterol ( = 0.009), c-reactive protein ( = 0.04), sodium ( = 0.01), and chloride ( = 0.002) plasma level variations. These results suggest the relative increase of the inter-cellular volume upon arrival, and subsequently its reduction to lower values than at baseline, indicating that even after 48 h the brain has not fully recovered to its equilibrium state. Even though serum electrolytes may only indirectly indicate modifications at the brain level due to the blood brain barrier, the results concerning osmolality suggest that body water might directly influence the change in cerebral ADC. These findings establish therefore a direct link between general brain inter-cellular water content and physiological biomarkers modifications produced by extreme sport.
2017International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease.BloodHuman herpesvirus-8 (HHV-8)-negative, idiopathic multicentric Castleman disease (iMCD) is a rare and life-threatening disorder involving systemic inflammatory symptoms, polyclonal lymphoproliferation, cytopenias, and multiple organ system dysfunction caused by a cytokine storm often including interleukin-6. iMCD accounts for one third to one half of all cases of MCD and can occur in individuals of any age. Accurate diagnosis is challenging, because no standard diagnostic criteria or diagnostic biomarkers currently exist, and there is significant overlap with malignant, autoimmune, and infectious disorders. An international working group comprising 34 pediatric and adult pathology and clinical experts in iMCD and related disorders from 8 countries, including 2 physicians that are also iMCD patients, was convened to establish iMCD diagnostic criteria. The working group reviewed data from 244 cases, met twice, and refined criteria over 15 months (June 2015 to September 2016). The proposed consensus criteria require both Major Criteria (characteristic lymph node histopathology and multicentric lymphadenopathy), at least 2 of 11 Minor Criteria with at least 1 laboratory abnormality, and exclusion of infectious, malignant, and autoimmune disorders that can mimic iMCD. Characteristic histopathologic features may include a constellation of regressed or hyperplastic germinal centers, follicular dendritic cell prominence, hypervascularization, and polytypic plasmacytosis. Laboratory and clinical Minor Criteria include elevated C-reactive protein or erythrocyte sedimentation rate, anemia, thrombocytopenia or thrombocytosis, hypoalbuminemia, renal dysfunction or proteinuria, polyclonal hypergammaglobulinemia, constitutional symptoms, hepatosplenomegaly, effusions or edema, eruptive cherry hemangiomatosis or violaceous papules, and lymphocytic interstitial pneumonitis. iMCD consensus diagnostic criteria will facilitate consistent diagnosis, appropriate treatment, and collaborative research.
2017Noninfectious prevertebral soft-tissue inflammation and hematoma eliciting swelling after anterior cervical discectomy and fusion.J Neurosurg SpineOBJECTIVE Anterior cervical discectomy and fusion (ACDF) procedures are performed to treat patients with cervical myelopathy or radiculopathy. Dysphagia is a post-ACDF complication. When it coincides with prevertebral space enlargement and inflammation, surgical site infection and pharyngoesophageal perforation must be considered. The association between dysphagia and prevertebral inflammation has not been reported. The authors investigated factors eliciting severe dysphagia and its relationship with prevertebral inflammation in patients who had undergone ACDF. MATERIALS The clinical data of 299 patients who underwent 307 ACDF procedures for cervical radiculopathy or myelopathy at Kushiro Kojinkai Memorial Hospital and Kushiro Neurosurgical Hospital between December 2007 and August 2014 were reviewed. RESULTS After 7 ACDF procedures (2.3%), 7 patients suffered severe prolonged and/or delayed dysphagia and odynophagia that prevented ingestion. In all 7 patients the prevertebral space was enlarged. In 5 (1.6%) the symptom was thought to be associated with prevertebral soft-tissue edema; in all 5 an inflammatory response, hyperthermia, and an increase in the white blood cell count and in C-reactive protein level was observed. After 2 procedures (0.7%), we noted prevertebral hematoma without an inflammatory response. None of the patients who had undergone 307 ACDF procedures manifested pharyngoesophageal perforation or surgical site infection. CONCLUSIONS Severe dysphagia and odynophagia are post-ACDF complications. In most instances they are attributable to prevertebral soft-tissue edema accompanied by inflammatory responses such as fever and an increase in the white blood cell count and in C-reactive protein. In other cases these anomalies are elicited by hematoma not associated with inflammation.
2017Anti-rheumatoid Arthritis Effect of Kaejadan via Analgesic and Antiinflammatory Activity in vivo and in vitro.Phytother ResAlthough Kaejadan (KJD), an herbal cocktail of three medicinal plants (Lithospermum erythrorhizon, Cinnamomum loureirii, and Salvia miltiorrhiza), has been traditionally used for the treatment of rheumatoid arthritis, its scientific evidence is not fully understood. Hence, we investigated antiinflammatory and analgesic mechanism of KJD in vivo and in vitro. Kaejadan suppressed the number of writhing responses in mice treated by acetic acid and showed antinociceptive effect by tail-flick test. Kaejadan abrogated serotonin or carrageenan or Freund's complete adjuvant (FCA)-induced paw edema and also reduced the level of Evans Blue for vascular permeability. Furthermore, KJD effectively reduced the positive responses for C-reactive protein and rheumatoid arthritis test in FCA-treated rats. Of note, KJD inhibited the level of lipid peroxide malondialdehyde and enhanced the level of superoxide dismutase in the hepatic tissues of FCA-treated rats. Additionally, KJD abrogated the levels of IL-1β and IL-6 in lipopolysaccharide and IFN-γ-exposed RAW 264.7 cells. Also, KJD reduced the expression of cyclooxygenase 2 or inducible nitric oxide synthase at protein and mRNA levels in IFN-γ and lipopolysaccharide-exposed RAW 264.7 cells. Overall, our findings demonstrate that KJD exerts antiinflammatory and analgesic effects via enhancement of antioxidant activity and inhibition of proinflammatory cytokines. Copyright © 2017 John Wiley & Sons, Ltd.
2017Brain Abscesses Associated with Asymptomatic Pulmonary Arteriovenous Fistulas.J Korean Neurosurg SocBrain abscess commonly occurs secondary to an adjacent infection (mostly in the middle ear or paranasal sinuses) or due to hematogenous spread from a distant infection or trauma. Pulmonary arteriovenous fistulas (AVFs) are abnormal direct communications between the pulmonary artery and vein. We present two cases of brain abscess associated with asymptomatic pulmonary AVF. A 65-year-old woman was admitted with a headache and cognitive impairment that aggravated 10 days prior. An magnetic resonance (MR) imaging revealed a brain abscess with severe edema in the right frontal lobe. We performed a craniotomy and abscess removal. Bacteriological culture proved negative. Her chest computed tomography (CT) showed multiple AVFs. Therapeutic embolization of multiple pulmonary AVFs was performed and antibiotics were administered for 8 weeks. A 45-year-old woman presented with a 7-day history of progressive left hemiparesis. She had no remarkable past medical history or family history. On admission, blood examination showed a white blood cell count of 6290 cells/uL and a high sensitive C-reactive protein of 2.62 mg/L. CT and MR imaging with MR spectroscopy revealed an enhancing lesion involving the right motor and sensory cortex with marked perilesional edema that suggested a brain abscess. A chest CT revealed a pulmonary AVF in the right upper lung. The pulmonary AVF was obliterated with embolization. There needs to consider pulmonary AVF as an etiology of cerebral abscess when routine investigations fail to detect a source.
2017Prognostic impact of intestinal wall thickening in hospitalized patients with heart failure.Int J CardiolIntestine-cardiovascular relationship has been increasingly recognized as a key factor in patients with heart disease. We aimed to identify the relationships among intestinal wall edema, cardiac function, and adverse clinical events in hospitalized heart failure (HF) patients.Abdominal computed tomographic images of 168 hospitalized HF patients were retrospectively investigated for identification of average colon wall thickness (CWT) from the ascending to sigmoid colon. Relationships between average CWT and echocardiographic parameters, blood sampling data, and primary outcomes including readmission for deteriorated HF and all-cause mortality were evaluated. Among the echocardiographic parameters, lower left ventricular diastolic function was correlated with higher average CWT. In multivariate analysis, higher logarithmic C-reactive protein level, lower estimated glomerular filtration rate, lower peripheral blood lymphocyte count, higher E/E' ratio, and extremely higher/lower defecation frequency were independently correlated with higher average CWT. Multivariate Cox-hazard analysis demonstrated that higher average CWT was independently related to higher incidence of primary outcomes.In hospitalized HF patients, increased CWT was associated with lower cardiac performance, and predicted poorer long-term clinical outcomes.
2017Risk factors for death in children during inpatient treatment of severe acute malnutrition: a prospective cohort study.Am J Clin NutrChildren who receive in-hospital treatment of severe acute malnutrition often have high mortality rates, and the reasons are not well understood.We assessed risk factors for death in children who were treated for malnutrition in a hospital.In a prospective observational study of 120 children who were receiving in-hospital treatment of severe acute malnutrition in Uganda with therapeutic formulas F-75 and F-100, we collected data on symptoms, clinical findings, plasma markers of refeeding syndrome (electrolytes and phosphate), and acute phase reactants, and recorded the nutritional therapy given in hospital.Seventeen children (14%) died. Clinical risk factors for death were the presence of oral thrush (HR: 5.0; 95% CI: 1.6, 15.2), a caretaker-reported severity of illness on a visual analog scale (HR: 1.7; 95% CI: 1.1, 2.6), impaired consciousness (HR: 16.7; 95% CI: 3.1, 90.4), and a capillary refill time >2 s (HR: 3.9; 95% CI: 1.4, 11.3). HIV infection was not associated with mortality (HR: 3.0; 95% CI: 0.7, 12.4), which was most likely due to low power. Biochemical risk factors were a plasma C-reactive protein concentration >15 mg/L on admission and low plasma phosphate that was measured on day 2 (HR: 8.7; 95% CI: 2.5, 30.1), particularly in edematous children. The replacement of F-75 with unfortified rice porridge to ameliorate diarrhea was associated with a higher risk of death, particularly if given during the first 2 d (HR: 5.0; 95% CI: 1.9, 13.3), which was an association that remained after adjustment for potential confounders (HR: 69.5; 95% CI: 7.0, 694.6).Refeeding syndrome may occur in children who are treated for malnutrition, even with moderately low plasma phosphate, and, in particular, in children with edematous malnutrition. The replacement of F-75 with unfortified rice porridge is associated with increased risk of death, which is possibly mediated by lowering plasma phosphate. The identified clinical risk factors may potentially improve the triage of children with malnutrition. This trial was registered at www.isrctn.com as ISRCTN55092738.
Nonarteritic anterior ischemic optic neuropathy following pars plana vitrectomy for macular hole treatment: case report.Arq Bras OftalmolHerein, we report a case of nonarteritic anterior ischemic optic neuropathy (NAION) following uneventful pars plana vitrectomy for macular hole treatment. A 56-year-old previously healthy woman presented with a full-thickness macular hole in right eye (OD) and small cup-to-disc ratios in both eyes. Five days after surgery, she noticed sudden painless loss of vision in OD and was found to have an afferent pupillary defect and intraocular pressure of 29 mmHg. Fundus examination showed right optic disc edema and the resolution of a macular hole with an inferior altitudinal visual field defect. Erythrocyte sedimentation rate, C-reactive protein levels, and general physical examination findings were normal. She was treated with hypotensive eyedrops and oral prednisone, resulting in mild visual improvement and a pale optic disc. A combination of face-down position and increased intraocular pressure due to a small optic disc cup were considered as potential mechanisms underlying NAION in the present case. Vitreoretinal surgeons should be aware of NAION as a potentially serious complication and be able to recognize associated risk factors and clinical findings.
2016Cytokine Elevation in Sudden Death With Respiratory Syncytial Virus: A Case Report of 2 Children.PediatricsRespiratory syncytial virus (RSV) is the most common viral cause of bronchiolitis and pneumonia in young children worldwide. Premature birth, bronchopulmonary dysplasia, congenital heart disease, and Down syndrome are risk factors for high mortality and prolonged morbidity after RSV infection. Conversely, many previously healthy, full-term children are also admitted to the hospital because of RSV, and some of them experience severe sequelae or die due to the virus. Various complications of RSV infection have been reported, such as encephalopathy, encephalitis, and cardiomyopathy. However, the pathogenesis of serious cases in children without an underlying disease has not been elucidated. In this report, we present 2 RSV-related deaths of children who were born at full-term and developed normally up to the age of 19 months. Their cardiopulmonary arrests occurred within half a day after the onset of symptoms, such as cough and high fever. Many postmortem examinations were performed to investigate their unexpected deaths. Histopathological examinations revealed extensive bronchiolitis and mild pneumonia accompanying airway obstruction. Immunostaining revealed the presence of the virus mainly in bronchial epithelia, but not in alveoli. Complete brain edema was prominent, and encephalopathy was developing. Blood tests revealed that the IL-6 level was elevated more than >200-fold above normal, despite a normal C-reactive protein level. Because IL-6 may reflect the severity of bronchial epithelial damage and contribute to brain edema, an extreme elevation of IL-6 may predict the risk for sudden death in children with RSV infection.
2017Corticosteroid transdermal delivery significantly improves arthritis pain and functional disability.Drug Deliv Transl ResArthritis is characterized by pain and functional limitation affecting the patients' quality of life. We performed a clinical study to investigate the efficacy of a betamethasone valerate medicated plaster (Betesil) in improving pain and functional disability in patients with arthritis and osteoarthritis. We enrolled 104 patients affected by osteoarthritis (n = 40) or arthritis (n = 64) in different joints. Patients received diclofenac sodium cream (2 g, four times a day) or a 2.25-mg dose of Betesil applied to the painful joint every night before bedtime for 10 days. Pain and functional disability were assessed, by the Visual Analogue Scale (VAS) and Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) scores. Redness was assessed by clinical inspection, and edema by the "fovea sign" method. C-reactive protein (CRP) was also measured; CRP can be used to cost-effectively monitor the pharmacological treatment efficacy and is increased during the acute-phase response, returning to physiological values after tissue recovery and functional restoration. All measurements were at baseline and at 10-day follow-up. At 10-day follow-up, a greater improvement in VAS and WOMAC pain and WOMAC stiffness and functional limitation scores from baseline was observed in patients treated with Betesil compared with diclofenac (all p < 0.01). At 10-day follow-up, improvement in redness, edema, and CRP levels from baseline was also greater in patients treated with Betesil compared with diclofenac (all p < 0.01). This study demonstrates the safety and efficacy of transdermal delivery of betamethasone valerate in patients affected by arthritis and osteoarthritis.
2016Autologous bone marrow stem cell transplantation for the treatment of ulcerative colitis complicated with herpes zoster: a case report.Front MedUlcerative colitis (UC) is a chronic inflammatory bowel disease with continuous or recurrent symptoms. A 42-year-old male patient with intermittent diarrhea accompanied by bloody mucopurulent stools was admitted to our hospital. The diagnosis of UC was confirmed by a combination of laboratory examination, colonoscopy, and histological assay. The patient developed herpes zoster in the hospital, which challenged traditional treatments. Therefore, we performed an autologous bone marrow cells to modulate the immune system with his permission. Autologous bone marrow mononuclear cells were collected and injected locally into the bowel mucosa, and subsequently injected systemically through a peripheral vein. After the patient underwent auto bone marrow mononuclear cells transplantations twice, the patient's symptoms were alleviated. Furthermore, he recovered from hematochezia, and his hypersensitive C reactive protein decreased. Colonoscopy results showed reduced lesions and decreased areas with bleeding and edema in the sigmoid colon and rectum. No recurrence occurred in the subsequent two years, but long-time monitoring is still necessary for the prophylaxis of colorectal cancer.
Limited diagnostic value of procalcitonin in early diagnosis of adult onset Still's disease.ReumatologiaA 17-year-old female patient was referred to the Infectious Diseases Ward because of fever lasting for 14 days. On admission to the hospital the patient was in a generally good state, without any abnormalities on physical examination. Laboratory investigation revealed elevated inflammatory markers. Diagnostic imaging comprising chest X-ray, abdominal ultrasonography, and echocardiography showed no abnormalities. During the hospitalization, there occurred episodes of fever with skin rash and musculoskeletal pain of the lower limbs. Procalcitonin concentrations continued to increase. C-reactive protein concentrations decreased during therapy, starting from 191 mg/l. On the 23 day of the disease, edema of the feet, ankles, and knees appeared. On the basis of the clinical picture and after excluding other possible causes of fever, the patient was diagnosed with adult onset Still's disease. The procalcitonin concentration was normalized after 5 days of steroid therapy. The patient was discharged under ambulatory rheumatologic supervision.
[Acute generalized exanthematous pustulosis induced by piroxicam].Rev Alerg MexBetween 62 and 90% of cases of acute generalized exanthematous pustulosis are caused by drugs. Its onset is rapid with generalized pustules, fever, and blood neutrophil count over 7000; pustules resolve spontaneously in less than 15 days. A case associated with piroxicam described.A 36-year-old with initial erythema of the thorax and abdomen, accompanied by burning, without fever, which later spread to his forearms, upper arms, and thighs, with face edema. A week earlier he had taken piroxicam for low back pain; at the time of hospitalization he received antihistamines, and topical and systemic steroids. Full blood count showed leukocytes at 8920, eosinophils at 600, neutrophils at 6600, total serum IgE at 188 UI, C-reactive protein at 2.9 mg/L, and no liver, kidney, or lung involvement. Treatment was initiated with intravenous antihistamines and ranitidine, saline, topical Vaseline plus topical mupirocin, and systemic steroids. On the second day of hospitalization neutrophils increased to 9000 and PCR to 3.3. The score to evaluate acute exanthematous pustulosis in the patient was 8, giving a definitive diagnosis.The differential diagnosis should be established primarily with pustular psoriasis. The prognosis is generally good, as reported.
2016Quantification of Bone Marrow Edema by Magnetic Resonance Imaging Only Marginally Reflects Clinical Neck Pain Evaluation in Rheumatoid Arthritis and Ankylosing Spondylitis.J RheumatolNeck pain is common in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). We investigated the correlation of bone marrow edema (BME) on magnetic resonance imaging (MRI) in RA and AS and its association with clinical complaints of neck pain.Cervical spine short-tau inversion recovery-MRI and T1w-MRI of 34 patients with RA and 6 patients with AS complaining about neck pain were obtained. Clinical and laboratory data were available. BME was scored by 2 blinded readers using a modification of a published score, including various cervical sites. Degenerative changes were also quantified.Patients were predominantly women (82.5%), and mean ± SD age was 57.5 ± 11.8 years, C-reactive protein (CRP) was 0.8 ± 1.3 mg/dl, and pain score was 46.0 ± 17.5. BME was detected in 24/40 patients (60%) involving the atlantoaxial region (21%), vertebral bodies (75%), facet joints (29%), and spinous processes (46%). Degenerative changes were identified in 21/40 patients (52.5%), 13 (62%) of whom also had BME in vertebral bodies. No differences were found between patients with versus without cervical BME for clinical assessments: numeric rating scale pain (median ± interquartile range) 5.5 ± 3.0 vs 6.0 ± 4.0 (p = 0.69), Funktionsfragebogen Hannover 68.2 ± 41.0 vs 42.0 ± 55.5 (p = 0.19), Northwick pain score 44.4 ± 21.8 vs 47.2 ± 27.0 (p = 0.83), or CRP 0.40 ± 0.80 vs 0.60 ± 0.66 (p = 0.94). For patients with degenerative changes, symptom duration was longer than for patients without (10 ± 12.5 vs 5.0 ± 18.0 yrs, p = 0.73).In this small study of patients with RA and AS complaining about neck pain, BME was found in many different cervical sites, including the facet joints and the spinous processes. However, the occurrence and severity of BME did not correlate with the severity of neck pain.
2016Elucidating the role of oxidative stress in the therapeutic effect of rutin on experimental acute pancreatitis.Free Radic ResAcute pancreatitis (AP) may be severe and cause hospitalization or death, and the available treatment is insufficient to control pancreatic inflammation and pain. Rutin is a natural flavonoid with the potential to treat AP via anti-inflammatory, antinociceptive, and antioxidant activities.This study investigated the beneficial effects of rutin on experimental AP induced by l-arginine administration in mice.The l-arginine-induced AP model was used in Swiss mice (n = 6-8). Mice submitted to AP induction were treated with rutin (37.5, 75, or 150 mg kg, p.o.) or vehicle (saline) after 24, 36, 48, and 60 h of AP induction. Abdominal hyperalgesia, serum enzymes, interleukin (IL)-6 levels, pancreatic inflammatory parameters, malondialdehyde (MDA) levels, antioxidant enzyme activities, and 3-nitrotyrosine contents were measured 72 h after induction.Mice submitted to l-arginine injections developed abdominal hyperalgesia and increased serum amylase, lipase, C-reactive protein and IL-6 concentrations; and increased pancreatic myeloperoxidase activity, edema index, MDA, and 3-nitrotyrosine contents. A marked decrease in catalase activity was observed in the pancreas without alterations of superoxide dismutase (SOD) activity compared with the control group. Rutin treatment significantly impaired all the parameters that were altered by AP induction, but increased catalase and SOD activities in the pancreas compared with the vehicle-treated group.Rutin treatment exerted a protective effect on l-arginine-induced AP by mechanisms involving the reduction of oxidative stress, which suggests that this flavonoid has a potential for future approaches designed for the management of AP.
2016Clinical significance of combined liver function and high-sensitivity C-reactive protein measurement in children with hand-foot-mouth disease.Genet Mol ResHand-foot-mouth disease (HFMD) is a common pediatric disease responsible for the development of rashes or herpes on the hand, foot, and mouth. Severe complications of HFMD include myocarditis, pulmonary edema, aseptic meningoencephalitis, and even death. Therefore, early diagnosis of HFMD is of particular importance. In this study, we determined the clinical value of the combined detection of liver function and high-sensitivity C-reactive protein (hs-CRP) expression in children with HFMD. Three hundred children with HFMD were recruited to this study between July 2013 and July 2015 and divided into the mild and severe HFMD groups (N = 150 per group). The liver function [aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels] and hs-CRP expression were evaluated using standardized tests, and the clinical value of combined detection of these indices (in parallel and serially) was determined. Patients in the severe HFMD group showed significantly higher levels of ALT, AST, ALP, and hs-CRP compared to those in the mild HFMD group (P < 0.05). The hs-CRP and liver function tests had low specificity and sensitivity, respectively. However, parallel combined detection improved the sensitivity and negative predicted value of these indices, whereas serial combined detection improved the specificity and positive predicted value. In conclusion, hs-CRP and liver function play a major role in the diagnosis of HFMD (and identifying its severity), and serial combined detection of these indices enhances the positive predicted value, and could be employed to diagnose severe HFMD at an earlier stage.
2017Remitting seronegative symmetrical synovitis with pitting edema syndrome complicated with primary lung cancer.Int Cancer Conf JRemitting seronegative symmetrical synovitis with pitting edema syndrome has been reported to be associated with malignant tumors. However, few cases occurring with lung cancer have been reported. We here report a case of remitting seronegative symmetrical synovitis with pitting edema syndrome complicated with lung cancer. A 77-year-old man presented with poly arthritis (both shoulders, knees, and hands), swelling of the hands, and an elevated C-reactive protein level. As the patient's rheumatoid factor was negative, he was diagnosed with remitting seronegative symmetrical synovitis with pitting edema syndrome. At the same time, computed tomography revealed a nodule suspicious of lung carcinoma in the right lower lobe. Right lower lobe lobectomy was performed, and the nodule was diagnosed as adenocarcinoma. Pathologically, pleural invasion and visceral pleural dissemination were detected, and the tumor was diagnosed as a primary lung carcinoma, p-T2aN0M1a, stage IV. During the preoperative interval, the remitting seronegative symmetrical synovitis with pitting edema syndrome had been successfully treated with prednisolone 20 mg/day, which was later reduced to 6 mg/day. Eighteen months after surgery, the patient's carcinoembryonic antigen levels increased, and the same symptoms recurred, this time more severely. We performed cranial magnetic resonance imaging and whole body positron emission tomography, but we did not detect any cancer recurrence. To treat the recurred remitting seronegative symmetrical synovitis with pitting edema syndrome, the patient has required not only prednisolone, but also azathioprine; however, the symptoms have not been controlled effectively. In our case, matrix metalloproteinase-3 levels were elevated, as shown in the tumor cells by immunohistochemistry. If higher matrix metalloproteinase-3 levels cause the symptoms, in our case, then remitting seronegative symmetrical synovitis syndrome might be considered a paraneoplastic syndrome. However, we could not conclusively determine if the subsequent reduction in matrix metalloproteinase-3 levels was the result of the surgery or the prednisolone treatment. Furthermore, based on the patient's progress following surgery, it is still not clear if the remitting seronegative symmetrical synovitis with pitting edema syndrome complicated with primary lung cancer in this case may be a paraneoplastic syndrome.
2016Case 234: Neuropathic Spondyloarthropathy.RadiologyHistory A 70-year-old woman presented to a peripheral hospital with signs and symptoms of acute chronic obstructive pulmonary disease (COPD) exacerbation. The patient also reported acute on chronic onset of thoracolumbar back pain over a period of 24 hours. She denied any history of recent trauma or intravenous drug use. She did not have any long-term indwelling catheters. The patient's medical history was also complicated by stage 4 renal failure from long-standing type II diabetes, hypertension, iron deficiency anemia, aortic stenosis, and prior bariatric surgery. The patient was not undergoing dialysis for her renal dysfunction, nor was she receiving steroids for COPD. On clinical examination, she was afebrile and tachypneic. Although she was not amenable to a full neurologic examination, she reported subjective leg weakness. There were no localizing signs or evidence of myelopathy. Perianal sensation and rectal tone were preserved. Pulmonary examination revealed wheezes and decreased basilar air entry. The patient's white blood cell count was 6.8 × 10(9)/L. Her blood chemistry was normal, aside from an elevated blood creatinine level of 158 mmol/L. Her erythrocyte sedimentation rate was elevated at 56 mm/h, and her C-reactive protein level was normal at 4.4 mg/L (41.9 nmol/L). Chest radiographs showed mild pulmonary edema with a small right pleural effusion. The patient was transferred to our facility for evaluation of findings on thoracic spine radiographs obtained at a peripheral hospital. Unenhanced thoracic spine magnetic resonance (MR) imaging was performed first and was followed by computed tomography (CT) to further delineate the findings. The patient's renal status precluded intravenous contrast material administration.
IgG4-related Disease Involving Multiple Organs with Elevated Serum Interleukin-6 Levels.Intern MedA 63-year-old woman presented to our hospital with elevated levels of serum IgG4, marked wall thickening of the gallbladder, hepatomegaly, and abdominal lymphadenopathy. She experienced a recurrent fever and leg edema. Her laboratory data demonstrated anemia, hypoalbuminemia, and elevated serum levels of interleukin-6 and C-reactive protein. The patient was eventually diagnosed with IgG4-related disease according to the comprehensive diagnostic criteria, although the patient exhibited common clinical manifestations of multicentric Castleman disease such as a fever, anemia, lymphadenopathy, and elevated levels of serum interleukin-6 and C-reactive protein. This case report highlights the difficulties in differentiating between these two diseases.
2016Small-Volume Adenosine, Lidocaine, and Mg2+ 4-Hour Infusion Leads to 88% Survival after 6 Days of Experimental Sepsis in the Rat without Antibiotics.Clin Vaccine ImmunolInnovative host-directed drug therapies are urgently required to treat sepsis. We tested the effect of a small-volume 0.9% NaCl adenosine, lidocaine, and Mg (ALM) bolus and a 4-h intravenous infusion on survivability in the rat model of polymicrobial sepsis over 6 days. ALM treatment led to a significant increase in survivability (88%) compared to that of controls (25%). Four controls died on day 2 to 3, and two died on day 5. Early death was associated with elevated plasma and lung inflammatory markers (interleukin-6 [IL-6], IL-1β, C-reactive protein), reduced white blood cell (WBC) count, hypoxemia, hypercapnia, acidosis, hyperkalemia, and elevated lactate, whereas late death was associated with a massive cytokine storm, a neutrophil-dominated WBC rebound/overshoot, increased lung oxidant injury, edema, and persistent ischemia. On day 6, seven of eight ALM survivors had inflammatory and immunological profiles not significantly different from those of sham-treated animals. We conclude in the rat model of experimental sepsis that small-volume ALM treatment led to higher survivability at 6 days (88%) than that of controls (25%). Early death in controls (day 2 to 3) was associated with significantly elevated plasma levels of IL-1β, IL-6, and C-reactive protein, severe plasma lymphocyte deficiency, reduced neutrophils, and acute lung injury. Late death (day 5) was associated with a massive neutrophil inflammatory storm, increased lung injury, and persistent ischemia. Possible mechanisms of ALM protection are discussed.
2016Newly diagnosed primary hypothyroidism applicant with massive pericardial effusion and acute renal failure.Endocr RegulWhile non-symptomatic pericardial effusion is seen in primary hypothyroidism, massive pericardial effusion is a very rare finding. In the literature, newly diagnosed primary hypothyroidism cases presenting with massive pericardial effusion or acute renal failure are present, but we did not encounter any case first presenting with combination of two signs. In this case report, primary hypothyroidism case that presenting with massive pericardial effusion and acute renal failure will be discussed. Subject and Results. Forty-eight years old male patient was hospitalized with shortness of breath, chest pain, swelling of the eyelids and bilateral limbs complaints. On chest radiograph heart shadow was deleted, pleural effusion was present until the middle zone of the left lung. Biochemical parameters (urea, creatinine, alanine aminotransferase aspartate aminotransferase, lactate dehydrogenase, sodium, potassium, creatine kinase, Troponin I, CK-MB, erythrocyte sedimentation rate, c-reactive protein) and thyroid stimulating hormone (TSH, 52.6 μg/ml), free triiodothyronine (T3, 0.61pg/ml), free thyroxine (T4, 0.12 ng/dl), anti thyroperoxydase (343 IU/ml), anti thyroglobulin (1604 IU/ml), were analyzed. The patient underwent pericardiocentesis. Levothyroxine treatment started with a dose of 0.05 mg per day and increased gradually until the optimum dose provided. At the end of the third month, the values of TSH, free T4, and free T3 were measured (2.3 μg/ml, 1.1 ng/dl, 2.54 pg/ml, respectively). The patient recovered completely and pericardial effusion was not detected in echocardiography.Massive PE and acute renal failure due to primary hypothyroidism is a rare clinical condition. Primary hypothyroidism should be kept in mind in patients with symptoms like shortness of breath, chest pain, and generalized edema; moreover, when acute renal failure and PE were detected. It should be considered that patient's biochemical parameters can improve starting from the two weeks after levothyroxine treatment started with pericardiocentesis in severe symptomatic patients.
2016Elevated blood plasma levels of epinephrine, norepinephrine, tyrosine hydroxylase, TGFβ1, and TNFα associated with high-altitude pulmonary edema in an Indian population.Ther Clin Risk ManagBiomarkers are essential to unravel the locked pathophysiology of any disease. This study investigated the role of biomarkers and their interactions with each other and with the clinical parameters to study the physiology of high-altitude pulmonary edema (HAPE) in HAPE-patients (HAPE-p) against adapted highlanders (HLs) and healthy sojourners, HAPE-controls (HAPE-c). For this, seven circulatory biomarkers, namely, epinephrine, norepinephrine, tyrosine hydroxylase, transforming growth factor beta 1, tumor necrosis factor alpha (TNFα), platelet-derived growth factor beta beta, and C-reactive protein (CRP), were measured in blood plasma of the three study groups. All the subjects were recruited at ~3,500 m, and clinical features such as arterial oxygen saturation (SaO2), body mass index, and mean arterial pressure were measured. Increased levels of epinephrine, norepinephrine, tyrosine hydroxylase, transforming growth factor-beta 1, and TNFα were observed in HAPE-p against the healthy groups, HAPE-c, and HLs (P<0.0001). CRP levels were decreased in HAPE-p against HAPE-c and HLs (P<0.0001). There was no significant difference or very marginal difference in the levels of these biomarkers in HAPE-c and HLs (P>0.01). Correlation analysis revealed a negative correlation between epinephrine and norepinephrine (P=4.6E-06) in HAPE-p and positive correlation in HAPE-c (P=0.004) and HLs (P=9.78E-07). A positive correlation was observed between TNFα and CRP (P=0.004) in HAPE-p and a negative correlation in HAPE-c (P=4.6E-06). SaO2 correlated negatively with platelet-derived growth factor beta beta (HAPE-p; P=0.05), norepinephrine (P=0.01), and TNFα (P=0.005) and positively with CRP (HAPE-c; P=0.02) and norepinephrine (HLs; P=0.04). Body mass index correlated negatively with epinephrine (HAPE-p; P=0.001) and positively with norepinephrine and tyrosine hydroxylase in HAPE-c (P<0.05). Mean arterial pressure correlated positively with TNFα in HAPE-p and norepinephrine in HLs (P<0.05). Receiver operating characteristic curve analysis yielded a positive predictive value for these biomarkers with HAPE (area under the curve >0.70, P<0.05). The results clearly suggest that increased plasma levels of these circulatory biomarkers associated with HAPE.
Intracerebral hemorrhage with a favorable outcome in a patient with childhood primary angiitis of the central nervous system.Rev Bras Reumatol Engl EdChildhood primary angiitis of the central nervous system (cPACNS) is a rare inflammatory brain disease of unknown etiology. Of note, brain hemorrhage has been rarely reported in cPACNS patients, generally associated with a delayed clinical diagnosis, or with a diagnosis only at necropsy. We present the case of a boy with cPACNS that previously suffered an ischemic stroke. At the age of 7 years and 10 months, he presented a sudden and severe headache, vomiting and reduction in consciousness level (Glasgow coma scale 7), requiring prompt tracheal intubation. Brain computed tomography demonstrated intraparenchymal hematoma in the right parieto-occipital lobe and a small focus of bleeding in the right frontal lobe, vasogenic edema, herniation of the uncus and a 10mm deviation to the left from the midline. C-reactive protein (9.2mg/dL) and von Willebrand factor (vWF) antigen (202%) were elevated. Decompressive craniotomy was performed and methylprednisolone and cyclophosphamide were administered. One week later, the patient had left hemiparesis without other sequelae. Importantly, motor deficits have been improving progressively. Our case reinforces the inclusion of this vasculitis as a differential diagnosis in children and adolescents with CNS hemorrhage.
2017Efficacy of vasopressin V2 receptor antagonist tolvaptan in treatment of hepatic edema.Hepatol ResTolvaptan, an oral active vasopressin V2 receptor antagonist, is widely used for hepatic edema in Japan, but its clinical benefits have yet to be fully clarified. The present study evaluated the efficacy of tolvaptan in hepatic edema.The efficacy and treatment regimen of tolvaptan were evaluated in 150 patients with hepatic edema by analyzing the initial (day 14) and long-term (day 90) responses to the drug and their predictive factors. All patients were divided into good (Child-Pugh classification B, and absent of advanced hepatocellular carcinoma) and poor hepatic condition groups, and the response rates were compared between the two groups.The initial response rate was 62%, and the long-term response rate was 47%. The assessment of predictive factors for response to tolvaptan showed that serum creatinine and C-reactive protein levels were important predictors of initial response, and that hepatic conditions, such as the Child-Pugh score or presence of hepatocellular carcinoma, as well as initial response, were significant predictors of long-term response. In addition, both the initial and long-term response rates and the cumulative survival rate were found to be higher in the good hepatic condition group than in the poor hepatic condition group, respectively (71% vs. 57%, P = 0.113; 62% vs. 39%, P = 0.009; log-rank test, P < 0.001).These results suggest that tolvaptan may provide high response rates when used early in the course of hepatic edema, or when both hepatic and renal functions are still retained, leading to an improved disease prognosis.
2017Timing of Symptomatic Infarct Swelling Following Intravenous Thrombolysis in Acute Middle Cerebral Artery Infarction: A Case-Control Study.Clin Appl Thromb HemostThe risk of symptomatic infarct swelling has been reported to be higher in patients treated with recombinant tissue plasminogen activator (rt-PA). The aim of this study was to evaluate the timing of symptomatic infarct swelling after rt-PA treatment.We retrospectively analyzed 14 868 patients with acute ischemic stroke from a stroke registry databank. We recruited patients with massive middle cerebral artery (MCA) infarction and symptomatic infarct swelling and excluded those with parenchymal or symptomatic hemorrhage. Multiple linear regression and multivariate logistic regression analyses were used to estimate the impact of rt-PA on the timing of symptomatic infarct swelling.A total of 23 patients with rt-PA treatment and 117 patients without rt-PA treatment were included. The rt-PA treatment group had a lower rate of coronary artery disease (8.7% vs 32.5%; P = .023), lower severity of baseline National Institutes of Health Stroke Scale score (19 vs 23; P = .014), shorter duration of infarct swelling (27.6 vs 45.4 hours; P < .001), and higher rate of hemicraniectomy surgery (65.2% vs 28.2%; P =.001) than those without rt-PA treatment. After adjusting for variables in multiple linear regression analysis, rt-PA treatment and an elevated C-reactive protein level were associated with early symptomatic infarct swelling ( P = .014 and P = .041, respectively). The rt-PA treatment was an independent factor related to early symptomatic infarct swelling within 36 hours ( P = .005; odds ratio [OR]: 5.3; confidence interval [CI]: 1.65-17.0) or 48 hours ( P = .009; OR: 16.4; CI: 2.00-134).Intravenous rt-PA treatment may hasten the onset of cerebral edema and subsequent cerebral herniation in large MCA territory infarction.
2016Case 232: Amyloid β-related Angiitis.RadiologyHistory A 78-year-old woman presented to a community hospital after an unwitnessed fall at her nursing home. Initial head computed tomography (CT) performed in the emergency department showed vasogenic edema in the right temporal parietal region, which prompted her transfer to our institution for additional work-up. Further history taking revealed recurrent transient motor and sensory transient ischemic attack-like symptoms over the preceding weeks. She denied having a fever or night sweats. There was no history of infection, bleeding, immunodeficiency, intravenous drug use, alcohol or tobacco abuse, malignancy, or genetic disorders. Her medical history included memory impairment and a left posterior cerebral artery territory infarction. She was not known to have any systemic inflammatory disorder. Physical examination findings at presentation were noncontributory. She was not taking any anticoagulants or immunosuppressive medication. Pertinent hematologic laboratory investigations revealed a white blood cell count of 6.7 × 10(9), a C-reactive protein level of 29 mg/L (276.2 nmol/L) (normal value, <10 mg/L [95.2 nmol/L]), and an erythrocyte sedimentation rate of 35 mm per hour (normal value, 0-10 mm per hour). Shortly after this patient was admitted to our institution, she had a generalized tonic-clonic seizure. Magnetic resonance (MR) imaging of the brain was performed the next day.
2017Clinical outcomes in the first year of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome.Mod RheumatolWe investigated clinical outcomes in patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome.This is a retrospective multicenter study conducted in Nagasaki, Japan. We consecutively diagnosed a total of 41 patients with RS3PE syndrome between October 2003 and September 2012 and evaluated their outcomes from medical records from the first year of follow-up.Although an excellent initial response to corticosteroids was noted in all 41 patients, 34 (82.9%) were still receiving corticosteroids and 13 (31.7%) showed elevated C-reactive protein (CRP) at one year. Multivariate analysis demonstrated that male gender and high CRP level at entry were independent variables associated with patients' one-year CRP level being ≥0.5 mg/dL. Odds ratios were 17.05 ([95% CI 2.41-370.12], p < 0.026) and 12.99 ([95% CI 1.78-269.62], p < 0.0096), respectively. Twenty-four patients (58.5%) were still receiving prednisolone (PSL) ≥ 5 mg/day at one year. Disease-modifying anti-rheumatic drugs including methotrexate were required in three patients (10.3%). Neoplasms were found in 14 patients (34.1%) and 1 of these had died due to lung cancer at one year.RS3PE syndrome initially responds well to corticosteroids with remission of symptoms. However, outcomes of RS3PE syndrome appear to be worse than expected, and may be influenced by gender and initial CRP level.
2016Myocardial Strain and Strain Rate in Kawasaki Disease: Range, Recovery, and Relationship to Systemic Inflammation/Coronary Artery Dilation.J Clin Exp CardiologKawasaki Disease (KD), a systemic vasculitis of medium sized vessels, is the most common cause of acquired heart disease among children in the developed world. Some KD patients demonstrate echocardiographic evidence of depressed myocardial mechanics. However, the incidence, etiology, and reversibility of abnormal mechanics in KD patients remain undefined.We retrospectively studied 41 KD patients and measured myocardial strain and strain rate by velocity vector imaging from pre-treatment and convalescent echocardiograms. Pre-treatment procalcitonin, C-reactive protein (CRP), and coronary artery z-scores were obtained in all patients and compared between the groups with preserved versus depressed acute phase mechanics. The change in mechanics between the acute and convalescent phases was also assessed. Patients with initially low longitudinal strain improved by the convalescent period (mean difference - 4.0%; p<0.005) with the greatest improvement occurring in patients with the lowest initial strain (-7.3%; p<0.05). Patients with higher initial strain did not change significantly by the convalescent period. Patients with lower longitudinal and circumferential strain demonstrated higher median procalcitonin levels (1.2 vs. 0.3 ng/mL; p<0.05 and 1.8 vs. 0.4 ng/mL; p<0.05 respectively) and a trend towards higher CRP, but no difference in coronary artery z-scores. Strain rate was not associated with inflammatory markers or coronary artery z-scores.The range of strain found in our cohort was large. Improvement in mean strain was driven primarily by patients with lower initial strain. Lower strain was associated with increased markers of systemic inflammation, but not proximal coronary artery changes.
2017Bilateral photoplethysmography for arterial steal detection in arteriovenous fistula using a fractional-order decision-making quantizer.Med Biol Eng ComputAs inflow and outflow stenoses worsen, both flow resistance and pressure increase in the stenotic vascular access. During dialysis, when blood flow decreases, it may retrograde from the peripheral artery through the palmar arch to the arterial anastomosis site. Arterial steal syndrome (ASS) causes distal hypoperfusion, resulting in hand ischemia or extremity pain and edema. Hence, this study proposes the bilateral photoplethysmography (PPG) for ASS detection in arteriovenous fistulas. The decision-making quantizer utilizes the fractional-order feature extraction method and a non-cooperative game (NCG) framework to evaluate the ASS risk level. Bilateral asynchronous PPG signals have significant differences in the rise time and amplitude in relation to the degree of stenosis. The fractional-order self-synchronization error formulation is a feature extraction method used to quantify bilateral differences in blood flow changes between the dexter and sinister PPG signals. The NCG model as a method of decision-making is then employed to evaluate the ASS risk level. Using an acoustic Doppler measurement, the resistive (Res) index is also used to evaluate the vascular access stenosis at the arterial anastomosis site. In contrast with alternative methods including the high-sensitivity C-reactive protein level or Res index, our experimental results indicate that the proposed decision-making quantizer is more efficient in preventing ASS during hemodialysis treatment.
2016Chronic oral administration of low-dose combination of fenofibrate and rosuvastatin protects the rat heart against experimentally induced acute myocardial infarction.Fundam Clin PharmacolFenofibrate and rosuvastatin at low doses might have experimental pleiotropic benefits. This study investigated the combined effect of low doses of fenofibrate and rosuvastatin in isoproterenol-induced experimental myocardial infarction. Rats administered isoproterenol (85 mg/kg/day, s.c.) for 2 days (day 29 and day 30) of 30 days experimental protocol developed significant myocardial infarction that was accompanied with high myocardial oxidative stress and lipid peroxidation, elevated serum markers of cardiac injury, lipid abnormalities, and elevated circulatory levels of C-reactive protein. Pretreatment with low doses of fenofibrate (30 mg/kg/day p.o., 30 days) and rosuvastatin (2 mg/kg/day p.o., 30 days) both alone or in combination markedly prevented isoproterenol-induced myocardial infarction and associated abnormalities while the low-dose combination of fenofibrate and rosuvastatin was more effective. Histopathological study in isoproterenol control rat heart showed necrosis with edema and acute inflammation at the margins of necrotic area. The rat heart from low-dose fenofibrate and rosuvastatin pretreated group showed scanty inflammation and no ischemia. In conclusion, fenofibrate and rosuvastatin pretreatment in low doses might have a therapeutic potential to prevent the pathogenesis of myocardial infarction. Moreover, their combined treatment option might offer superior therapeutic benefits via a marked reduction in myocardial infarct size and oxidative stress, suggesting a possibility of their pleiotropic cardioprotective action at low doses.
2016Antilipidemic effects and gene expression profiling of the glycosaminoglycans from cricket in rats on a high fat diet.Arch Pharm ResGlycosaminoglycan (GAG) from cricket (Gryllus bimaculatus) was studied as a potential health supplement. Antiatherosclerotic and antilipidemic effects of the GAG of G. bimaculatus (GbG, 5 or 10 mg/kg) were investigated in 15-week old Wistar rats treated with GbG for over a month. GbG produced a meaningful anti-edema effect with inhibition of C-reactive protein (CRP). Also, the weights of abdominal and epididymidal fat were also reduced in conjunction with a mild increase in body weight. Furthermore, the sero-biochemical parameters showed an antihyperlipidemic effect with decreased levels of phospholipid, AST, ALT, total cholesterol and glucose in a dose-dependent manner. In addition anticoagulant and antithrombotic effects were seen: platelet, thrombin time, prothrombin time and Factor I were increased with GbG treatment. Furthermore, the GbG treated rat group (at 10 mg/kg) compared to control, showed that 588 genes (test/control ratio >2.0) including lipocalin 2 (Lcn2) and alpha 2-macroglobulin (A2 m) were up-regulated, and 569 genes (test/control ratio >0.5) including stearoyl-coenzyme A desaturase 1 (Scd1) were down-regulated. Based on these results, GbG could potentially prevent or treat fatty liver or hyperlipidemia in rats on a high-fat diet.
2016Early Cartilage Changes After Anterior Cruciate Ligament Injury: Evaluation With Imaging and Serum Biomarkers-A Pilot Study.ArthroscopyTo determine if magnetic resonance imaging markers of cartilage matrix and morphology and circulating serum biomarkers of inflammation and matrix degradation differ over time in patients with anterior cruciate ligament (ACL) injury and bone marrow edema lesions (BMELs) when compared with matched control subjects.We performed a case-control study, in which 11 ACL-injured subjects scheduled to undergo reconstruction and 11 matched control subjects were scheduled for testing. Participants were selected for the ACL reconstruction (ACLR) group if they injured their ACL while participating in sports, were aged 14 to 30 years, had 1 or more BMELs, and were scheduled to undergo bone-patellar tendon-bone ACLR. Testing required patients to undergo magnetic resonance imaging for measurement of T2 relaxation times in standardized regions of interest over the medial and lateral tibial plateaus and femoral condyles and have blood drawn for measurement of cartilage oligomeric matrix protein (COMP) and C-reactive protein levels before ligament reconstruction and 1 year after surgery.ACL patients had prolonged T2 relaxation times, indicative of cartilage matrix degradation, in the superficial central lateral tibial plateau (P = .02) and deep medial tibial plateau when compared with control subjects (P = .0001). Prolonged T2 relaxation times were also noted over the lateral femoral condyle at baseline for ACL patients compared with control subjects (P = .001), but the differences resolved by 1 year (P = .98). Circulating serum COMP levels were greater in ACL patients (233.23 ± 88.26 ng/mL) compared with control subjects (169.05 ± 64.53 ng/mL, P = .05).T2 mapping showed prolonged relaxation times in the lateral compartment of the knee in ACLR patients with lateral BMELs. Furthermore, prolonged T2 relaxation times were apparent in the medial compartment of the knee in ACL-injured patients where bone marrow lesions were not present. Higher serum COMP levels were present in ACL-injured subjects when compared with control subjects.Level II, prospective case-control study.
2016Acute bilateral uveitis and right macular edema induced by a single infusion of zoledronic acid for the treatment of postmenopausal osteoporosis as a substitution for oral alendronate: a case report.BMC Musculoskelet DisordZoledronic acid-induced uveitis (ZAIU) is rare but severe, and has been recently considered part of an acute phase reaction. Only 15 cases have been reported since 2005. Here we describe a case with macular edema, which is the first reported case observed after long-term alendronate tolerance.A 63-year-old Asian woman received her first intravenous zoledronic acid treatment for the management of postmenopausal osteoporosis as a more convenient substitute for oral alendronate. Twenty-four hours later, bilateral eye irritations, periorbital swelling, blurred vision, and diplopia presented. The complete blood count and transaminase levels were normal, but the erythrocytic sedimentation, C-reactive protein, and serum C4 levels were elevated. On detailed ophthalmological examination, a diagnosis of bilateral acute uveitis and macular edema in the right eye was made. The ocular symptoms were not improved until administration of topical and oral steroids. Complete resolution was achieved. There was no rechallenge of bisphosphonates, and no recurrence at 6 months follow-up. Based on an extensive review, abnormal fundus is rarely reported, especially in cases of macular edema. Rechallenge with zoledronic acid in five cases induced no additional uveitis, and changing the medication to pamidronate in another patient was also tolerated. Interestingly, our patient suffered from uveitis soon after intravenous zoledronate exposure after a two-year tolerance to oral alendronate.This is the first report of zoledronic acid induced uveitis with macular edema after long-term alendronate tolerance. Prior oral alendronate may not entirely prevent ZAIU. Steroids are usually necessary in the treatment of ZAIU. Bisphosphonate rechallenge is not fully contraindicated, and prior steroid administration may be a more reasonable treatment choice according to the available evidence.
2016Candida Arthritis: Analysis of 112 Pediatric and Adult Cases.Open Forum Infect DisBackground.  Candida arthritis is a debilitating form of deeply invasive candidiasis. However, its epidemiology, clinical manifestations, management, and outcome are not well understood. Methods.  Cases of Candida arthritis were reviewed from 1967 through 2014. Variables included Candida spp in joint and/or adjacent bone, underlying conditions, clinical manifestations, inflammatory biomarkers, diagnostic imaging, management, and outcome. Results.  Among 112 evaluable cases, 62% were males and 36% were pediatric. Median age was 40 years (range, <1-84 years). Most patients (65%) were not pharmacologically immunosuppressed. Polyarticular infection (≥3 joints) occurred in 31% of cases. Clinical manifestations included pain (82%), edema (71%), limited function (39%), and erythema (22%) with knees (75%) and hips (15%) most commonly infected. Median erythrocyte sedimentation rate was 62 mm/hr (10-141) and C reactive protein 26 mg/dL (0.5-95). Synovial fluid median white blood cell count was 27 500/µL (range, 100-220 000/µL) with 90% polymorphonuclear neutrophils (range, 24-98). Adjacent osteomyelitis was present in 30% of cases. Candida albicans constituted 63%, Candida tropicalis 14%, and Candida parapsilosis 11%. Most cases (66%) arose de novo, whereas 34% emerged during antifungal therapy. Osteolysis occurred in 42%, joint-effusion in 31%, and soft tissue extension in 21%. Amphotericin and fluconazole were the most commonly used agents. Surgical interventions included debridement in 25%, irrigation 10%, and drainage 12%. Complete or partial response was achieved in 96% and relapse in 16%. Conclusion.  Candida arthritis mainly emerges as a de novo infection in usually non-immunosuppressed patients with hips and knees being most commonly infected. Localizing symptoms are frequent, and the most common etiologic agents are C albicans, C tropicalis, and C parapsilosis. Management of Candida arthritis remains challenging with a clear risk of relapse, despite antifungal therapy.
2016Antiphospholipids Syndrome Complicated by a Systemic Capillary Leak-Like Syndrome Treated With Steroids and Intravenous Immunoglobulins: A Case Report.Medicine (Baltimore)This report describes the onset of systemic capillary leak (SCL)-like syndrome in a 30-year-old woman with antiphospholipids syndrome (APS) during puerperium.Twelve hours after a cesarean section, she presented a sudden fever and abdominal pains followed by dyspnea, severe edema of the limbs and pelvis.Computer tomography shows congestion of interstitial pulmonary parenchyma, pericardial and pleural effusion, edema of intestinal wall and of perivisceral adipose tissue, and periportal lymphedema. Laboratory tests showed neutrophilic leukocytosis, hypoalbuminemia, and an increase of erythrocyte sedimentation rate and C-reactive protein. Because fever and raised inflammation parameters are not observed in idiopathic capillary leak syndrome (SCLS; Clarkson disease), a diagnosis of SCL-like syndrome was made.Albumin solution, high-dose methylprednisolone and intravenous immunoglobulins (IVIG) infusion were administered with a rapid improvement of her clinical condition.The prompt treatment with steroids and IVIG likely prevented the life-threatening shock syndrome that can occur in SCLS, with acute hypotensive attacks, and severe limbs edema requiring fasciotomy.All clinical and laboratory findings supported autoinflammation as the underlying pathogenic mechanism of the syndrome. The data indicate that SCL-like syndrome can be considered a novel clinical syndrome, which can complicate APS.
2016Surgical treatment strategy for diabetic forefoot osteomyelitis.Wound Repair RegenThe aim of this study was to propose an appropriate surgical treatment for diabetic forefoot osteomyelitis (DFO) involving ischemia or moderate to severe soft tissue infection. The records of 28 patients with osteomyelitis from 2009 to 2015 were retrospectively studied. All patients had undergone surgery based on preoperative magnetic resonance imaging examinations and histopathological or culture analyses confirming the surgical bone margin. The appropriate surgical margin, crucial factors for early healing, and prognosis after complete resection of osteomyelitis were examined. After healing, patients were followed up to assess prognosis (range 32-1,910 days, median 546 days). The healing rate of nonischemic cases of DFO with negative surgical margins was 100% and that of ischemic cases was 84.6%; the ambulatory rates for both types of cases were 100%. No wound (and/or osteomyelitis) recurrence was observed. Nine new cases of DFO developed in six patients (21.4%; eight were due to vascular stenosis, and one was due to biomechanical changes in the foot. After complete resection of osteomyelitis, preoperative and postoperative C-reactive protein levels and the size of the ulcer were significant predictors of early healing (p < 0.05, 0.01, and 0.05, respectively). The appropriate surgical margin should be set in the area of bone marrow edema, based on magnetic resonance imaging examinations after revascularization. In cases with high preoperative or postoperative C-reactive protein levels, long-term antibiotic therapy is recommended, and surgery should be planned after the C-reactive protein levels decrease, except in emergencies.
2016Evaluation of treatments for sacroiliitis in spondyloarthropathy using the Spondyloarthritis Research Consortium Canada scoring system.Arthritis Res TherIn this study, the Spondyloarthritis Research Consortium Canada (SPARCC) scoring method was used to compare treatment methods in patients with axial spondyloarthritis (SpA), a form of sacroiliitis. MRI abnormalities in bone marrow edema (BME) were compared before and after treatment in order to compare the efficacy of anti-TNF-α and DMARD, alone or in combination, as treatments for sacroiliitis.Fifty-six Chinese patients with axial SpA (mean age 22.6 years) were recruited. Patients were divided into three groups according to different treatments (anti-TNF-α alone vs. DMARDs alone vs. combined anti-TNF-α and DMARDs). MRI examinations were performed before and after treatment. The SPARCC score, clinically relevant AS Disease Activity (ASDAS) indices, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were analyzed.After treatment, ASDAS and SPARCC scores, ESR, and CRP were significantly improved (P < 0.05) in the anti-TNF-α monotherapy and combination groups; however, there were no statistically significant differences (P > 0.05) in clinical disease activity and radiological inflammation of sacroiliac joint (SIJ) in patients in the DMARDs alone group. SPARCC showed a correlation with ASDAS score pre-treatment, but not post-treatment. Furthermore, there were significant changes (P < 0.05) in these patients with axial SpA after only 3 months of treatment. Follow-up studies of patients who continued therapy for 4-6 months and 9-12 months revealed statistically significant differences from baseline (P < 0.05).SPARCC can be used to assess severity of disease pre-treatment. Anti-TNF-α treatment resulted in effective reduction of disease activity and BME of SIJ after 3 months of therapy.
2016MRI and clinical features of Langerhans cell histiocytosis (LCH) in the pelvis and extremities: can LCH really look like anything?Skeletal RadiolTo assess clinical and MRI features of Langerhans cell histiocytosis in the pelvis and extremities.The MRI and clinical features of 21 pathologically proven cases of LCH involving the pelvis and extremities were studied. Multiple characteristics of the lesions were evaluated (location, size, T1/ T2/post-contrast features, perilesional bone and soft tissue signal, endosteal scalloping, periosteal reaction, soft tissue mass, pathologic fracture). Pre-biopsy radiologic diagnoses were collected from the original clinical reports. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), temperature, and white blood cell count (WBC) were collected at the time of diagnosis when available.The locations of the LCH lesions included five humerus, four femur, five ilium, one tibia, one clavicle, and three scapula. Lesional size ranged from 1.8 to 7.1 cm, with a mean of 3.6 cm. All lesions demonstrated perilesional bone marrow edema, periosteal reaction, endosteal scalloping, and post-contrast enhancement. An associated soft tissue mass was present in 15/21 (71.4 %). Clinically, the WBC, ESR, and CRP were elevated in 2/14 (14 %), 8/12 (67 %), and 4/10 (40 %) of cases, respectively. Fever was documented in 1/15 (7 %) patients and pain was reported in 15/15 (100 %).The clinical and radiologic features of LCH in the pelvis and extremities overlap with infection and malignancy, but LCH must be considered in the differential diagnosis, as it routinely presents with aggressive MRI features, including endosteal scalloping, periosteal reaction, perilesional edema, and a soft tissue mass. Furthermore, an unknown skeletal lesion at presentation without aggressive MRI features is unlikely to represent LCH.
2016Changes in plasma phosphate during in-patient treatment of children with severe acute malnutrition: an observational study in Uganda.Am J Clin NutrChildren treated for severe acute malnutrition (SAM) are at risk of refeeding hypophosphatemia. Therapeutic diets have only recently become fortified with phosphorus to meet United Nations (UN) specifications, but to our knowledge no studies have investigated the effect.The aim was to assess concentrations and correlates of plasma phosphate (P-phosphate) at admission and during treatment and to identify correlates of changes in P-phosphate.This was a prospective observational study in 6- to 59-mo-old children admitted for treatment of SAM to Mulago Hospital, Uganda. P-phosphate was measured at admission, on the second day of treatment with a therapeutic formula containing 75 kcal/100 mL and 560 mg phosphorus/L (F-75, Nutriset), at the start of the transition to a therapeutic formula containing 100 kcal/100 mL and 579 mg phosphorus/L (F-100; Nutriset), at day 2 of transition, and at discharge.Among 120 children, mean ± SD P-phosphate at admission was 1.04 ± 0.31 mmol/L and increased by 0.43 (95% CI: 0.35, 0.52) mmol/L during the first 2 d and more slowly toward discharge. Most (79%) children experienced their lowest P-phosphate concentration at admission, and none developed severe hypophosphatemia. P-phosphate was lowest in children with edema and with elevated C-reactive protein, and a lower increase was seen with increasing caretaker-reported severity of illness. Partially or fully replacing F-75 with rice porridge (i.e., a local practice to reduce diarrhea) during the first 2 d of stabilization was associated with a 0.34-mmol/L (95% CI: 0.18, 0.50 mmol/L) lower increase in P-phosphate during the same first 2 d.F-75, which complies with UN specifications and provides 73 mg phosphorus · kg(-1) · d(-1) (130 mL · kg(-1) · d(-1)), seems to prevent refeeding hypophosphatemia in children with SAM. Replacing this formula with rice porridge during the first days of treatment to manage diarrhea may have an adverse effect on P-phosphate concentrations. This study was registered at http://www.isrctn.com as ISRCTN55092738.
2015[Protein-losing enteropathy with systemic lupus erythematosus effectively treated with octreotide and medium chain triglyceride diet: A case report].Nihon Rinsho Meneki Gakkai KaishiIn January 2009, a 62-year-old man presented with diarrhea, leg edema, and thrombopenia and was admitted to our hospital. The past medical history revealed Sjögren's syndrome and autoimmune hepatitis for which he had been administered prednisolone. On admission, a laboratory examination revealed massive hypoalbuminemia and high levels of C-reactive protein and platelet-associated IgG. Anti-double stranded DNA and anti-Sm antibodies were negative. Analysis of the bone marrow aspirate and Tc-99m albumin scintigraphy findings suggested autoimmune thrombocytopenic purpura (AITP) and protein-losing enteropathy (PLE), respectively. We diagnosed him as SLE, because past immunoserological testing had showed positivity for anti-double stranded DNA antibody and LE cells. Methylprednisolone pulse therapy and intravenous immunoglobulin therapy were ineffective. Rituximab was ineffective against PLE but was effective against AITP. Cyclosporine and Cyclophosphamide were ineffective against PLE. Subcutaneous injection of 200-μg octreotide daily and a medium chain triglyceride (MCT) diet was effective against PLE, and the patient's condition dramatically improved. The effectiveness of octreotide treatment and an MCT diet in the treatment of PLE with SLE is discussed.
2016Febuxostat protects rats against lipopolysaccharide-induced lung inflammation in a dose-dependent manner.Naunyn Schmiedebergs Arch PharmacolThe aim of the present work was to investigate possible protective effects of febuxostat, a highly potent xanthine oxidase inhibitor, against acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats. Male Sprague Dawley rats were randomly divided into six groups, as follows: (i) vehicle control group; (ii) and (iii) febuxostat 10 and febuxostat 15 groups, drug-treated controls; (iv) LPS group, receiving an intraperitoneal injection of LPS (7.5 mg/kg); (v) and (vi) febuxostat 10-LPS and febuxostat 15-LPS groups, receiving oral treatment of febuxostat (10 and 15 mg/kg/day, respectively) for 7 days before LPS. After 18 h administration of LPS, blood was collected for C-reactive protein (CRP) measurement. Bronchoalveolar lavage fluid (BALF) was examined for leukocyte infiltration, lactate dehydrogenase (LDH) activity, protein content, and total nitrate/nitrite. Lung weight gain was determined, and lung tissue homogenate was prepared and evaluated for oxidative stress. Tumor necrosis factor-α (TNF-α) was assessed in BALF and lung homogenate. Moreover, histological changes of lung tissues were evaluated. LPS elicited lung injury characterized by increased lung water content (by 1.2 fold), leukocyte infiltration (by 13 fold), inflammation and oxidative stress (indicated by increased malondialdehyde (MDA), by 3.4 fold), and reduced superoxide dismutase (SOD) activity (by 34 %). Febuxostat dose-dependently decreased LPS-induced lung edema and elevations in BALF protein content, infiltration of leukocytes, and LDH activity. Moreover, the elevated levels of TNF-α in BALF and lung tissue of LPS-treated rats were attenuated by febuxostat pretreatment. Febuxostat also displayed a potent antioxidant activity by decreasing lung tissue levels of MDA and enhancing SOD activity. Histological analysis of lung tissue further demonstrated that febuxostat dose-dependently reversed LPS-induced histopathological changes. These findings demonstrate a significant dose-dependent protection by febuxostat against LPS-induced lung inflammation in rats.
2016Associations Between Spondyloarthritis Features and Magnetic Resonance Imaging Findings: A Cross-Sectional Analysis of 1,020 Patients With Persistent Low Back Pain.Arthritis RheumatolThe Assessment of SpondyloArthritis international Society (ASAS) has previously published criteria for spondyloarthritis (SpA). In the Spines of Southern Denmark cohort, which included patients with persistent low back pain and an unknown proportion of patients with SpA, our objectives were 1) to estimate the prevalence of magnetic resonance imaging (MRI) findings and clinical features included in the ASAS criteria for SpA and 2) to explore the associations between MRI findings and clinical features.We included patients ages 18-40 years with persistent low back pain who had been referred to the Spine Centre of Southern Denmark. We collected information on clinical features (including HLA-B27 and high-sensitivity C-reactive protein) and MRI findings in the spine and sacroiliac (SI) joints.Of 1,020 included patients, 537 (53%) had at least 1 of the clinical features included in the ASAS criteria for SpA. Three clinical features were common-inflammatory back pain according to the ASAS criteria, a good response to nonsteroidal antiinflammatory drugs (NSAIDs), and family history of SpA. The prevalence of these features ranged from 15% to 17%. Sacroiliitis on MRI according to the ASAS definition was present in 217 patients (21%). Of those 217 patients, 91 (42%) had the minimum amount of bone marrow edema required according to the ASAS definition (a low bone marrow edema score). The presence of HLA-B27, peripheral arthritis, a good response to NSAIDs, and preceding infection were independently positively associated with MRI findings in the SI joints (odds ratios [ORs] of 1.9-9.0). The remaining 8 clinical features were not positively associated with MRI findings. Importantly, only age was independently associated with low bone marrow edema score at the SI joints (OR of 1.1 per year).In this population, 53% had at least 1 clinical feature included in the ASAS criteria for SpA, and 21% had sacroiliitis according to the ASAS definition; furthermore, the associations between the clinical and imaging domains were inconsistent. The results indicate a need for further investigation of the importance of these findings in SpA, including investigation of the minimum requirements for defining sacroiliitis on MRI.
2016Clinical Features and Outcomes of Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-associated Inflammation: Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS).Clin Infect DisKaposi sarcoma herpesvirus (KSHV) is the cause of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and a form of Castleman disease (KSHV-MCD). Recently a KSHV-associated inflammatory cytokine syndrome (KICS) distinct from KSHV-MCD was reported.We prospectively characterized the clinical, laboratory, virologic and immunologic features of KICS by evaluating symptomatic adults with KSHV using a prespecified definition. These features and overall survival were compared with controls from 2 prospectively characterized human immunodeficiency virus (HIV)-infected cohorts, including 1 with KSHV coinfection.All 10 KICS subjects were HIV infected males; 5 had HIV viral load (VL) suppressed <50 copies mL (median 72, range <50-74 375); all had KS and 2 also had PEL. All had multiple severe symptoms attributable to KICS: median number of symptoms 8 (6-11), median grade of worst symptom 3 (2-4). These included gastrointestinal disturbance (present in 9); edema (9); respiratory (6); and effusions (5). Laboratory abnormalities included anemia (all); hypoalbuminemia (all) and thrombocytopenia (6). None developed KSHV-MCD; 6 died with median survival from KICS diagnosis 13.6 months. KICS subjects compared with controls had more severe symptoms; lower hemoglobin and albumin; higher C-reactive protein; higher KSHV VL; elevated interleukin (IL)-6 and IL-10; and an increased risk of death (all P < .05). Anemia and hypoalbuminemia at presentation were independently associated with early death.KICS subjects demonstrated diverse severe symptoms, a high rate of KSHV-associated tumors, high mortality, and a distinct IL-6/IL-10 signature. KICS may be an important unrecognized cause of morbidity and mortality, including symptoms previously ascribed to HIV. Exploration of KSHV-directed therapy is warranted.
2016A multicenter prospective cohort study of volume management after subarachnoid hemorrhage: circulatory characteristics of pulmonary edema after subarachnoid hemorrhage.J NeurosurgOBJECT Subarachnoid hemorrhage (SAH) is often accompanied by pulmonary complications, which may lead to poor outcomes and death. This study investigated the incidence and cause of pulmonary edema in patients with SAH by using hemodynamic monitoring with PiCCO-plus pulse contour analysis. METHODS A total of 204 patients with SAH were included in a multicenter prospective cohort study to investigate hemodynamic changes after surgical clipping or coil embolization of ruptured cerebral aneurysms by using a PiCCO-plus device. Changes in various hemodynamic parameters after SAH were analyzed statistically. RESULTS Fifty-two patients (25.5%) developed pulmonary edema. Patients with pulmonary edema (PE group) were significantly older than those without pulmonary edema (non-PE group) (p = 0.017). The mean extravascular lung water index was significantly higher in the PE group than in the non-PE group throughout the study period. The pulmonary vascular permeability index (PVPI) was significantly higher in the PE group than in the non-PE group on Day 6 (p = 0.029) and Day 10 (p = 0.011). The cardiac index of the PE group was significantly decreased biphasically on Days 2 and 10 compared with that of the non-PE group. In the early phase (Days 1-5 after SAH), the daily water balance of the PE group was slightly positive. In the delayed phase (Days 6-14 after SAH), the serum C-reactive protein level and the global end-diastolic volume index were significantly higher in the PE group than in the non-PE group, whereas the PVPI tended to be higher in the PE group. CONCLUSIONS Pulmonary edema that occurs in the early and delayed phases after SAH is caused by cardiac failure and inflammatory (i.e., noncardiogenic) conditions, respectively. Measurement of the extravascular lung water index, cardiac index, and PVPI by PiCCO-plus monitoring is useful for identifying pulmonary edema in patients with SAH.
2015Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage.Acta Pharm Sin BIschemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage.
2016Biological activity of a small molecule indole analog, 1-[(1H-indol-3-yl)methylene]-2-phenylhydrazine (HMPH), in chronic inflammation.Chem Biol InteractA synthetic small molecule, 1-[(1H-indol-3-yl)methylene]-2-phenylhydrazine (HMPH) was conveniently synthesised by a one-step reaction, purified and characterised by chromatographic and spectroscopic methods. HMPH scavenged free radicals and inhibited lipopolysaccharide (LPS)-induced ROS generation and NO release in RAW-264.7 cells without signs of any detectable cytotoxicity. HMPH inhibited lipid peroxidation (LPO) with IC50 of 135 ± 9 as against 58 ± 8 μM for α-tocopherol. Further, HMPH (>50 μM) significantly reduced the LPS-induced TNF-α release in mouse peritoneal macrophages and in human peripheral blood mononuclear cells (PBMCs). HMPH did not show any visible signs of toxicity in rats up to 400 mg/kg/intraperitoneal and 2000 mg/kg/oral. HMPH at 25 and 50 mg/kg attenuated neutrophil infiltration in air-pouch lavage and bronchoalveolar lavage (BAL) in rat models. HMPH also reduced myeloperoxidase (MPO), nitrite and TNF-α in air-pouch lavage in addition to MPO in plasma. HMPH reduced acute paw-inflammation in carrageenan-induced paw-edema. HMPH consistently decreased both ipsilateral and contralateral paw inflammation, minimised the clinical scores of arthritis, prevented body weight (B.wt.) loss, attenuated serum C-reactive protein (C-RP) and rheumatoid factors (RF) in rat model of adjuvant-induced arthritis. Histopathology and radio-graphical reports show that HMPH reduced bone erosion in both ipsilateral and contralateral paw joints. Failure to inhibit COX suggests that effectiveness of HMPH in both acute and chronic inflammation is mediated by a multimodal mechanism involving modulation of immunity, attenuating TNF-α, protecting bone attrition and reducing oxidative stress.
2015Inflammatory Biomarkers in Refractory Congestive Heart Failure Patients Treated with Peritoneal Dialysis.Biomed Res IntProinflammatory cytokines play a pathogenic role in congestive heart failure. In this study, the effect of peritoneal dialysis treatment on inflammatory cytokines levels in refractory congestive heart failure patients was investigated. During the treatment, the patients reached a well-tolerated edema-free state and demonstrated significant improvement in NYHA functional class. Brain natriuretic peptide decreased significantly after 3 months of treatment and remained stable at 6 months. C-reactive protein, a plasma marker of inflammation, decreased significantly following the treatment. Circulating inflammatory cytokines TNF-α and IL-6 decreased significantly after 3 months of peritoneal dialysis treatment and remained low at 6 months. The reduction in circulating inflammatory cytokines levels may be partly responsible for the efficacy of peritoneal dialysis for refractory congestive heart failure.
2015C-reactive protein enhances murine antibody-mediated transfusion-related acute lung injury.BloodTransfusion-related acute lung injury (TRALI) is a syndrome of respiratory distress triggered by blood transfusions and is the leading cause of transfusion-related mortality. TRALI has primarily been attributed to passive infusion of HLA and/or human neutrophil antigen antibodies present in transfused blood products, and predisposing factors such as inflammation are known to be important for TRALI initiation. Because the acute-phase protein C-reactive protein (CRP) is highly upregulated during infections and inflammation and can also enhance antibody-mediated responses such as in vitro phagocytosis, respiratory burst, and in vivo thrombocytopenia, we investigated whether CRP affects murine antibody-mediated TRALI induced by the anti-major histocompatibility complex antibody 34-1-2s. We found that BALB/c mice injected with 34-1-2s or CRP alone were resistant to TRALI, however mice injected with 34-1-2s together with CRP had significantly enhanced lung damage and pulmonary edema. Mechanistically, 34-1-2s injection with CRP resulted in a significant synergistic increase in plasma levels of the neutrophil chemoattractant macrophage inflammatory protein-2 (MIP-2) and pulmonary neutrophil accumulation. Importantly, murine MIP-2 is the functional homolog of human interleukin-8, a known risk factor for human TRALI. These results suggest that elevated in vivo CRP levels, like those observed during infections, may significantly predispose recipients to antibody-mediated TRALI reactions and support the notion that modulating CRP levels is an effective therapeutic strategy to reduce TRALI severity.
Effects of nutritional supplementation with l-arginine on repair of injuries due to muscle strain: experimental study on rats.Rev Bras OrtopTo evaluate the influence of oral supplementation with arginine on regeneration of injuries due to straining of the anterior tibial muscle of rats.Twenty-four Wistar rats of weight 492.5 ± 50.45 g were used. Injuries were induced through straining the anterior tibial muscles. The rats were separated into three groups of eight rats each. In the untreated group (UTG), after induction of injuries, the rats were observed for 24 h. In the simulation group (SG) and the arginine group (AG) respectively, the rats received isotonic saline solution and arginine solution via direct gavage, over a seven-day period. At the end of the period, blood samples were collected for serum evaluations of creatine kinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST) and C-reactive protein (CRP). The right and left anterior tibial muscles were resected for histopathological evaluations on the muscle injuries, investigating edema, hemorrhage and disorganization or morphometric alteration of the muscle fibers. The tissue repair was investigated in terms of proliferation of adipose tissue, angiogenesis and collagen fibers. The ANOVA and Student's t methods were used and p ≤ 0.05 was taken to be statistically significant.In the serum evaluations, the AG showed lower CK assay values and higher AST values. In the histopathological evaluation, the UTG presented edema and hemorrhage compatible with injuries due to strain; the SG presented edema and hemorrhage with proliferation of adipose tissue and collagen fibers; and the AG presented not only the findings of the SG but also, especially, intense angiogenesis.Oral supplementation with arginine did not cause any significant metabolic alterations that would contraindicate its use and it induced angiogenesis during the repair of muscles injured due to strain.
2016Serum and Aqueous Concentrations of Inflammatory Markers in Diabetic Macular Edema.Ocul Immunol InflammTo investigate the relationship between the serum and aqueous levels of inflammatory markers and diabetic macular edema (DME).The study included four patient groups: the healthy control group (n = 23 eyes); the diabetic control group (n = 22 eyes); the groups with and without DME (n = 20 eyes and n = 22 eyes, respectively). The patients were evaluated based on their serum levels of HbA1c, C-reactive protein (CRP) and serum and aqueous levels of tumor necrosis factor-alpha (TNF-α).Statistically significant differences were present for the serum CRP levels and for the aqueous TNF-α levels between the healthy control group and the group with DME (p = 0.004 and p = 0.03, respectively); for the serum TNF-α levels between the healthy control group and the groups without and with DME (p = 0.009 and p = 0.001, respectively).Increased serum levels of CRP and serum and aqueous levels of TNF-α in DME suggest that inflammation is involved in the pathogenesis of DME.
2015L-carnitine reduces acute lung injury in experimental biliary obstruction.Saudi Med JTo investigate the protective effects of L-carnitine (LC) on lungs in an experimental obstructive jaundice (OJ) model.This was conducted for 2 months between May 2011 and July 2011 at Suleyman Demirel University School of Medicine Experimental and Clinical Research Center, Isparta, Turkey. Thirty-eight Wistar-Albino rats with an average weight of 250-300 g were divided into 3 groups of control, OJ, and OJ + L-carnitine treatment (LCT). L-carnitine was injected intravenously into the tail vein at a dose of 50 mg/kg/day for 10 days to the LCT group. Animals were sacrificed 10 days later. Enzyme levels were measured in the lung tissue; malondialdehyde, myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), catalase, and superoxide dismutase. Tumor necrosis factor-alfa, interleukin 6 (IL-6), IL-8, and C-reactive protein levels were studied in plasma samples. Histopathological changes in the lungs were examined. There was a decreased in GSH-Px, MPO, and IL-8 levels (p less than 0.05) in the LCT group. The histopathological examination showed that neutrophil leukocyte infiltration and edema formation decreased and destruction of lung parenchyma disappeared following the treatment with LC (p less than 0.05). L-carnitine has a protective effect against lung damage due to experimental obstructive jaundice, possibly by altering anticytokine and antioxidant activity, and by decreasing the neutrophil migration.
2015Studies on ageing and the severity of radiographic joint damage in rheumatoid arthritis.Arthritis Res TherThe western population is ageing. It is unknown whether age at diagnosis affects the severity of Rheumatoid Arthritis (RA), we therefore performed the present study.1,875 RA-patients (7,219 radiographs) included in five European and North-American cohorts (Leiden-EAC, Wichita, Umeå, Groningen and Lund) were studied on associations between age at diagnosis and joint damage severity. In 698 Leiden RA-patients with 7-years follow-up it was explored if symptom duration, anti-citrullinated-peptide-antibodies (ACPA), swollen joint count (SJC) and C-reactive-protein (CRP) mediated the association of age with joint damage. Fifty-six other RA-patients of the EAC-cohort underwent baseline MRIs of wrist, MCP and MTP-joints; MRI-inflammation (RAMRIS-synovitis plus bone marrow edema) was also evaluated in mediation analyses. Linear regression and multivariate normal regression models were used.Analysis on the five cohorts and the Leiden-EAC separately revealed 1.026-fold and 1.034-fold increase of radiographic joint damage per year increase in age (β=1.026, 1.034, both p<0.001); this effect was present at baseline and persisted over time. Age correlated stronger with baseline erosion-scores compared to joint space narrowing (JSN)-scores (r=0.38 versus 0.29). Symptom duration, ACPA, SJC and CRP did not mediate the association of age with joint damage severity. Age was significantly associated with the MRI-inflammation-score after adjusting for CRP and SJC (β=1.018, p=0.027). The association of age with joint damage (β=1.032, p=0.004) decreased after also including the MRI-inflammation-score (β=1.025, p=0.021), suggesting partial mediation.RA-patients presenting at higher age have more severe joint damage; this might be partially explained by more severe MRI-detected inflammation at higher age.
2015A case of penetration of the intestinal wall by a soft-shelled turtle bone successfully removed with double-balloon endoscopy.Clin J GastroenterolA 62-year-old male was admitted to our hospital due to left lower abdominal pain. Three days before admission, he ate seafood in a Japanese restaurant. Two days before admission, he suffered from intermittent left lower abdominal pain. One day before admission, he developed a high fever and subsequently visited our hospital the following day. Localized tenderness and rebound pain were observed in the left lower abdomen, and C-reactive protein was elevated. Computed tomography revealed a linear high-density object in the distal portion of the small intestine accompanied by edema of the wall, suggesting penetration by something like a fishbone. On the ninth hospital day, double-balloon endoscopy was performed via the transanal route. Yellow foreign material was found in the ileum and was then successfully removed with biopsy forceps. The removed material measured 3 mm in width, 3 cm in length and was slightly curved. It proved to be a bone of the forefoot of a soft-shelled turtle, which had been included on the menu of the restaurant. The patient was completely cured and discharged on the 14th hospital day.
2016Assessment of Sacroiliitis at Diagnosis of Juvenile Spondyloarthritis by Radiography, Magnetic Resonance Imaging, and Clinical Examination.Arthritis Care Res (Hoboken)To evaluate the prevalence of sacroiliitis at diagnosis of juvenile spondyloarthritis (SpA) and the accuracy of physical examination and back pain to detect sacroiliitis, using imaging as the reference standard.We performed a prospective cross-sectional study of 40 children with newly diagnosed juvenile SpA and 14 healthy controls. Subjects were assessed using physical examination, anteroposterior pelvic radiograph, and pelvic magnetic resonance imaging (MRI). Differences in clinical features between those children with and without sacroiliitis were assessed by Fisher's exact test for categorical variables and Wilcoxon's rank sum test for continuous variables. Accuracy of physical examination and back pain for detection of sacroiliitis was determined using MRI as the reference standard. Predicted probability of sacroiliitis was determined using exact multivariate logistic regression.Eight children (20%) with juvenile SpA had active sacroiliitis. Of those subjects with active changes on MRI, 7 of 8 (88%) also had evidence of erosions or sclerosis. Five children (13%) with juvenile SpA and 1 control (7%) had nonperiarticular bone marrow edema. Of the subjects with active sacroiliitis, only 3 (38%) reported a history of back pain or tenderness on palpation of the sacroiliac joints. The positive and negative predictive values of clinical examination features and back pain for detection of sacroiliitis were low. The estimated probability of having sacroiliitis was 0.84 (95% confidence interval 0.40-1.00) in HLA-B27-positive patients with an elevated C-reactive protein (CRP) level.Active sacroiliitis by MRI is common at diagnosis in juvenile SpA and is frequently asymptomatic. Children who are HLA-B27-positive and have elevated CRP levels have the highest probability of sacroiliitis.
2015[Qangxin Granule Intervened Chronic Heart Failure Rats with Xin-qi Deficiency Complicated Blood Stasis and Edema Syndrome: an Experimental Study].Zhongguo Zhong Xi Yi Jie He Za ZhiTo study and evaluate the curative effect and mechanism of Qiangxin Granule (QXG) in intervening chronic heart failure (CHF) rats with Xin-qi deficiency complicated blood stasis and edema syndrome (XQD-BS-ES).Totally 72 SD rats of clean grade were randomly divided to the normal control group (n =10) and the model group (n = 62). The XQD-BS-ES rat model was established by adriamycin plus propylthiouracil method. Survived modeled rats were then randomly divided to 5 groups i.e., the model group (n = 11, administered with normal saline by gastrogavage), the Western medicine (WM) group (n =11 , administered with perindopril and hydrochlorothiazide by gastrogavage), the low dose QXG (QXG(L)) group (n = 11, administered with 9.26 g/kg QXG by gastrogavage), the middle dose QXG (QXG(M)) group (n = 11, administered with 18.52 g/kg QXG by gastrogavage), the high dose QXG (QXG(H)) group (n = 11, administered with 37.04 g/kg QXG by gastrogavage). After 4 weeks of treatment, left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), brain natriuretic peptide (BNP), heart rate (HR), respiratory rate (RR), urine output, ear temperature, exhaustive swimming test (EST), tri-iodothyronine (T3), tetra-iodothyronine (T4), thyroid stimulating hormone (TSH), as well as heart, lung, liver weight index and their pathological sections, and high sensitivity C-reactive protein (HS-CRP), angiotensin II (Ang II), carbohydrate antigen 125 (CA125) were detected and compared.Compared with the normal control group, LVEF, LVFS, BNP, HR, RR, urine output, ear temperature, EST, T3, T4, TSH, HS-CRP, Ang II, and CA125 changed significantly in the model group (P < 0.01). Compared with the model group after treatment, LVEF, LVFS, BNP, urine output, EST, T4, heart and liver weight index, HS-CRP, Ang II, CA125 were significantly improved in each QXG group (P < 0.05, P < 0.01). Moreover, TSH was improved in the QXGL and QXG(M) groups (P < 0.05); ear temperature and T3 in the QXG(M) were also improved (P < 0.05); the lung weight index decreased in the QXG(M) and QXG(H) groups (P < 0.01). Compared with the WM group, T4 and CA125 were obviously improved in all QXG groups (P < 0.01); BNP and ear temperature were obviously improved in QXG(L) and QXG(M) groups (P < 0.05, P < 0.01); LVEF, LVFS and TSH were obviously improved in the QXG(M) group (P < 0.05, P < 0.01). And as far as each treatment group, LVEF, LVFS, urine output increased significantly after treatment (P < 0.01); EST obviously increased in QXG(M) and QXG(H) groups (P < 0.01); ear temperature increased in all QXG groups (P < 0.05, P < 0.01). Moreover, compared with the model group, pathological changes of heart, lung, and liver were improved to some degree in each treatment group, especially in the QXG(M) group.Good curative effect was shown in each QXG group. QXG could improve LVEF, LVFS and BNP of CHF rats of XQD-BS-ES, as well as T3, T4, TSH, EST, urine output, and ear temperature. Moreover, QXG showed superiority than WM group in this respect.
2015The impact of sub-clinical over-hydration on left ventricular mass in peritoneal dialysis patients.Int J Clin Exp MedLeft ventricular hypertrophy (LVH) represents a major predictor of the development of cardiovascular (CV) complications. Over-hydration (OH) is an important uremic risk factor associated with LVH and increased CV morbidity and mortality in peritoneal dialysis (PD) patients. In the present study we evaluated the prevalence of sub-clinical OH (SCOH) among PD patients and its effects on left ventricular mass (LVM).In this cross sectional study hydration status, blood pressure, glucose load, systemic inflammation and LVM were evaluated in 43 clinically stable patients on maintenance PD for 24-76 months. The hydration status was assessed by whole-body bio-impedance spectroscopy (BIS). Peripheral edema and any evidence of pulmonary congestion were considered clinical signs of OH.OH ≥ 1.5 L was detected in 26 (60.5%) of the study participants; the OH in 19 (73.1%) of them was sub-clinical. Only 23.5% (4/17) of patients with OH < 1.5 L had LVH compared to 68.4% (13/19) of those with SCOH ≥ 1.5 L (P = 0.007). Compared to patients with OH < 1.5 L, patients with SCOH ≥ 1.5 L had higher levels of blood pressure, peritoneal glucose load, plasma brain natriuretic peptide, high sensitive C-reactive protein, interleukin-6 and LVMI; and lower levels of serum albumin (P < 0.001). No significant differences were found between patients with clinical OH or SCOH with OH ≥ 1.5 L.SCOH is highly prevalent among PD patients and may contribute to the development of LVH. Considering the poor prognosis associated with over-hydrated PD patients, periodic assessment of hydration status using accurate BIS is suggested.
2015[Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) -associated glomerulonephritis with acute pancreatitis: a case report].Nihon Jinzo Gakkai ShiWe report here a case of a 64-year-old woman with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) -associated glomerulonephritis who developed acute pancreatitis. The patient was admitted to our hospital because of abnormal urinalysis findings, edema, and progressive renal failure. Laboratory studies showed a high white blood cell count (11,570/μL), anemia (hemoglobin 7.8 g/dL), and elevated serum creatinine (2.36 mg/dL) and C-reactive protein (12.20 mg/dL) levels. Furthermore, the MPO-ANCA titer was very high (1,625 U/mL, normal range < 10 U/mL). Histopathological findings of the renal biopsy were consistent with microscopic polyangiitis. Accordingly, we diagnosed MPO-ANCA-associated glomerulonephritis. On the day after the renal biopsy, the patient complained of low back pain. Computed tomography (CT) revealed postbiopsy hemorrhage. Thereafter, the patient's symptoms and laboratory studies gradually worsened. A repeat CT performed a few days later revealed no changes in the perirenal hematoma; however, an enlarged pancreas head was incidentally observed. There was no obvious cause of acute pancreatitis, and MPO-ANCA-associated vasculitis, although rare, was suspected as the cause. We initiated prednisolone pulse therapy for vasculitis along with the administration of nafamostat mesilate and ulinastatin for acute pancreatitis. Subsequently, the levels of pancreatic enzymes gradually increased, but several days later, abdominal magnetic resonance imaging showed improvement in the pancreas head. The pancreatitis gradually resolved over time. Acute pancreatitis occurring concurrently with MPO-ANCA-associated glomerulonephritis is extremely rare. To our knowledge, only a few such cases have been reported and have suggested that steroid therapy may play a role in triggering pancreatic involvement. In our case, however, an enlarged pancreas head was observed before steroid therapy was initiated. Therefore, we consider our case to be very rare.
2015Diffuse large B-cell lymphoma presenting with central pontine myelinolysis: a case report.J Med Case RepThe most common cause of central pontine myelinolysis is an overly rapid correction of hyponatremia, although it can also occur in patients with any condition leading to nutritional or electrolyte stress. We report a case of diffuse large B-cell lymphoma with central pontine myelinolysis developing at the onset of disease. To the best of our knowledge, hematological malignancies presenting with central pontine myelinolysis have been rarely reported, especially in previously untreated patients, as in our case report.A 78-year-old Japanese woman presented to a neighborhood clinic with persistent high fever, edema, and general weakness. Despite the absence of specific neurological findings, brain magnetic resonance imaging showed an abnormal lesion in the central pons area of her brain (hyperintense on T2-weighted and hypointense on T1-weighted sequences), compatible with central pontine myelinolysis. She was admitted to our emergency department in a state of shock one month later. The results of her blood tests showed greatly elevated C-reactive protein and lactate dehydrogenase levels. She had severe hypoalbuminemia and mild hyponatremia, and showed signs of disseminated intravascular coagulation. Mild bilateral pleural effusion, prominent subcutaneous edema, and splenomegaly were detected on her systemic computed tomography scan. Her body fluid cultures did not show signs of infection and her spinal aspiration did not show pleocytosis or abnormal cells. A diagnosis of diffuse large B-cell lymphoma was made based on the results of her bone marrow examination. As she was critically ill before the diagnosis was made, she was treated with methylprednisolone pulse therapy, followed by systemic chemotherapy (rituximab with modified THP-COP regimen, including cyclophosphamide, pirarubicin, vindesine, and prednisolone), which resulted in complete remission and recovery without any neurological defects, and resolution of her abnormal findings on magnetic resonance imaging.Central pontine myelinolysis is a serious condition that may result in neuropathological sequelae and mortality, and clinicians should be aware of its potential presence in patients with malignancies.
2015Effects of emergency cervical cerclage on pregnancy outcome: a retrospective study of 158 cases.Med Sci MonitThe aim of this study was to evaluate the effectiveness and safety of emergency cervical cerclage in women with advanced cervical dilatation and bulging of fetal membranes. The study included 158 women who underwent emergency cervical cerclage because of cervix dilatation and protruding membranes in mid-trimester at Sun Yat-sen Memorial Hospital of Sun Yat-sen University. Pregnancy outcomes and pregnancy outcome related to clinical features were analyzed retrospectively. Analysis revealed that the placement of emergency cerclage led to the delivery of live infants with a success rate of 82.28%. The mean interval between cerclage and delivery was 52.16.±26.62 days, with a mean gestation at delivery of 30.3±4.7 weeks and a mean birth weight of 1934.69±570.37 g. No severe maternal complications such as maternal death, hematosepsis, and hysterorrhexis occurred after the operation. Two women (1.25%) had laceration of the cervix, 1 woman (0.61%) suffered pulmonary edema, and 2 women (1.25%) developed deep vein thrombosis (DVT). There were significant correlations between the pregnancy outcome and risk factors, including any presenting symptoms, cervical dilatation, postoperative white blood cell count, and C-reactive protein (CRP) value. No significant difference was found in women with good vs. poor outcome in terms of maternal age and obstetric histories. Emergency cervical cerclage is effective in prolonging pregnancy and improving neonatal outcome in women with cervical incompetence. It should be considered a viable option for women with a dilated cervix in mid-trimester.
2015[Correlation of RANKL/OPG, dickkopf-1 and bone marrow edema in rheumatoid arthritis with the complaint of knee pain].Sichuan Da Xue Xue Bao Yi Xue BanTo investigate the correlation of the receptor activator of nuclear factor kappa-B ligand (RANKL)/serum osteoprotegerin (OPG) system, Dickkopf-1 (DKK-1) and bone marrow edema (BME) in rheumatoid arthritis (RA) with the complaint of knee pain.The clinical data of 50 cases of RA with the complaint of knee pain were collected. According to MRI finding, half of them (25 cases) had bone marrow edema (BME). Each patient received the measurement of serum OPG, RANKL, DKK-1, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti cyclic citrullinated peptide antibody (CCP), rheumatoid factort(RF). The clinical symptoms, disease activity score 28 (DAS28), were compared between BME and non-BME griups, and the correlation between RANKL/OPG system, DKK-1 and BME of RA was analyzed.Compared with non BME group, BME group had shorter course (P=0.000), higher DAS28 score (P=0.009), CRP (P=0:000), RF (P=0.033) and CCP (P=0.012). lower level of serum OPG (P=0.000), higher level of RANKL (P=0.000), RANKL/OPG (P=0.000), and DKK-1 (P=0.001). The severity of bone marrow edema was correlated with the serum RANKL (volume r(s)=0.31, P=0.027; degree r(s)=0.33, P=0.022), RANKL/OPG (volume r(s)=0.29, P=0.039; degree r(s)=0.28, P=0.043), DKK-1 (volume r(s)=0.33, P=0.021; degree r(s)=0.34, P=0.019).BME is one of the early signs of bone erosion in RA, there were more active inflammation, autoantibodies, and osteocasts in RA patients with BME.
2015Fatal water intoxication and cardiac arrest in runners during marathons: prevention and treatment based on validated clinical paradigms.Am J MedCerebral edema due to exercise-associated hyponatremia and cardiac arrest due to atherosclerotic heart disease cause rare marathon-related fatalities in young female and middle-aged male runners, respectively. Studies in asymptomatic middle-aged male physician-runners during races identified inflammation due to skeletal muscle injury after glycogen depletion as the shared underlying cause. Nonosmotic secretion of arginine vasopressin as a neuroendocrine stress response to rhabdomyolysis mediates hyponatremia as a variant of the syndrome of inappropriate antidiuretic hormone secretion. Fatal hyponatremic encephalopathy in young female runners was curtailed using emergent infusion of intravenous hypertonic (3%) saline to reverse cerebral edema on the basis of this paradigm. This treatment was arrived at through a consensus process within the medical community. An increasing frequency of cardiac arrest and sudden death has been identified in middle-aged male runners in 2 studies since the year 2000. Same-aged asymptomatic male physician-runners showed post-race elevations in interleukin-6 and C-reactive protein, biomarkers that predict acute cardiac events in healthy persons. Hypercoagulability with in vivo platelet activation and release of cardiac troponin and N-terminal pro-brain natriuretic peptide were also observed post-race in these same subjects. High short-term risk for atherothrombosis during races as shown by stratification of biomarkers in asymptomatic men may render nonobstructive coronary atherosclerotic plaques vulnerable to rupture. Pre-race aspirin use in this high-risk subgroup is prudent according to conclusive evidence for preventing first acute myocardial infarctions in same-aged healthy male physicians. On the basis of validated clinical paradigms, taking a low-dose aspirin before a marathon and drinking to thirst during the race may avert preventable deaths in susceptible runners.
2015The effect of a single dose of prednisolone in dogs envenomated by Vipera berus--a randomized, double-blind, placebo-controlled clinical trial.BMC Vet ResTreatment with glucocorticoids after snakebite in dogs is controversial and randomized clinical studies are missing. The objective of this study was to investigate the effect of a single dose of prednisolone in dogs envenomated by Vipera berus in a double-blind placebo-controlled study, after exclusion of dogs treated with antivenom. The two treatment groups were compared regarding clinical status and clinicopathological test results. A total of 75 dogs bitten by Vipera berus within the previous 24 hours were included. Clinical assessment, blood sampling and measurement of the bitten body part were done at admission (Day 1), after 24 hours (Day 2) and at a re-examination (Re-exam) after 10-28 days. Dogs were given prednisolone 1 mg/kg bodyweight (PRED) or saline (PLACEBO) subcutaneously in a randomized, double-blind clinical trial. Dogs were examined clinically and mental status and extent of edema were described. Furthermore, appetite, vomiting, diarrhea, cardiac arrhythmia and death were recorded. Concentrations of C-reactive protein (CRP) and high sensitivity cardiac Troponin I (cTnI), hematology variables and Prothrombin time (PT) were determined. Systemic inflammation was defined as present if CRP > 35 mg/l.None of the dogs died during the study period. The mental status was reduced in 60/75 (80%) of dogs on Day 1, compared to 19/75 (25%) on Day 2. The proportion of dogs with no or only mild edema increased significantly from Day 1 to Day 2. About one-third of the dogs developed gastrointestinal signs during the study period. Cardiac arrhythmia was uncommon. Clinicopathological changes included increased total leucocyte count, CRP and troponin concentration on Day 2. The cTnI concentration was increased in dogs with systemic inflammation, compared to dogs without systemic inflammation. A single dose of prednisolone did not significantly affect any of the clinical or clinicopathological parameters studied, except for a higher monocyte count on Day 2 in dogs that had received prednisolone treatment.The results of the present study do not support routine administration of a single dose of prednisolone 1 mg/kg subcutaneously in dogs bitten by Vipera berus.
2015Effect of chronic khat (Catha edulis, Forsk) use on outcome of Plasmodium berghei ANKA infection in Swiss albino mice.BMC Infect DisThe objective of this study was to explore effects of khat (Catha edulis) on outcome of rodent malaria infection and its anti-plasmodial activities on Plasmodium berghei ANKA (PbA).Female Swiss albino mice were orally treated with crude khat (Catha edulis) extracts (100, 200 and 300 mg/kg) on a daily basis for 4 weeks prior to PbA infection. Physical, clinical, hematological, biochemical and histo-pathological features of the mice were assessed. In addition, in vivo anti-plasmodial activities of khat were evaluated.The finding of this study showed that khat use was strongly associated with increment of levels of liver and kidney biomarkers, leucopenia, severe anemia, rise in level of inflammation biomarkers: C-reactive protein (CRP), uric acid (UA), increased monocyte-lymphocyte count ratio (MLCR), manifestation of cerebral malaria symptoms such as ataxia, paralysis and deviation of the head but with no pulmonary edema. Significantly lower level of parasitemia (P<0.05), rectal temperature, but, high level of hemoglobin were observed at the early stage of the PbA infection in khat treated mice than the control. With extension of the treatment period, however, drastic increments were observed in parasite load and rectal temperature although there was reduction in hemoglobin (Hb) level. Moreover, khat showed poor anti-plasmodial activity with <10% parasite suppression activity and lack protection against major malaria symptoms. The significant reduction (P<0.01) of hematological parameters during PbA infection strengthen the notion that hematological parameters could be good predictors of severe malaria complications in human.In mice model treated with khat prior to infection with the rodent malaria parasite, khat was found to worsen manifestation of most malaria complications. Furthermore, the same plant showed poor in vivo anti-plasmodial activity and protection against major malaria symptoms.
2015Heme oxygenase-1 protects corexit 9500A-induced respiratory epithelial injury across species.PLoS OneThe effects of Corexit 9500A (CE) on respiratory epithelial surfaces of terrestrial mammals and marine animals are largely unknown. This study investigated the role of CE-induced heme oxygenase-1 (HO-1), a cytoprotective enzyme with anti-apoptotic and antioxidant activity, in human bronchial airway epithelium and the gills of exposed aquatic animals. We evaluated CE-mediated alterations in human airway epithelial cells, mice lungs and gills from zebrafish and blue crabs. Our results demonstrated that CE induced an increase in gill epithelial edema and human epithelial monolayer permeability, suggesting an acute injury caused by CE exposure. CE induced the expression of HO-1 as well as C-reactive protein (CRP) and NADPH oxidase 4 (NOX4), which are associated with ROS production. Importantly, CE induced caspase-3 activation and subsequent apoptosis of epithelial cells. The expression of the intercellular junctional proteins, such as tight junction proteins occludin, zonula occludens (ZO-1), ZO-2 and adherens junctional proteins E-cadherin and Focal Adhesion Kinase (FAK), were remarkably inhibited by CE, suggesting that these proteins are involved in CE-induced increased permeability and subsequent apoptosis. The cytoskeletal protein F-actin was also disrupted by CE. Treatment with carbon monoxide releasing molecule-2 (CORM-2) significantly inhibited CE-induced ROS production, while the addition of HO-1 inhibitor, significantly increased CE-induced ROS production and apoptosis, suggesting a protective role of HO-1 or its reaction product, CO, in CE-induced apoptosis. Using HO-1 knockout mice, we further demonstrated that HO-1 protected against CE-induced inflammation and cellular apoptosis and corrected CE-mediated inhibition of E-cadherin and FAK. These observations suggest that CE activates CRP and NOX4-mediated ROS production, alters permeability by inhibition of junctional proteins, and leads to caspase-3 dependent apoptosis of epithelial cells, while HO-1 and its reaction products protect against oxidative stress and apoptosis.
2015Glasgow prognostic score predicts prognosis for cancer patients in palliative settings: a subanalysis of the Japan-prognostic assessment tools validation (J-ProVal) study.Support Care CancerThe Glasgow prognostic score (GPS), which uses C-reactive protein and albumin levels, is a good predictor of prognosis in cancer patients undergoing anti-tumor therapy. The objective of this study was to investigate the correlation between GPS and survival among cancer patients in palliative settings, as findings in such populations have not been well described.This was a subanalysis of a multicenter, prospective, cohort study in patients who were adults, diagnosed with advanced cancer, and first referred to palliative care service in Japan. Patients who were not receiving anti-tumor therapy and who had undergone laboratory examinations were eligible. Clinical features were analyzed to investigate prognostic factors.A total of 1160 patients were enrolled (41.6 % female; median age, 72 years). The independent predictors were Eastern Cooperative Oncology Group performance status (ECOG PS) score of 4 (hazard ratio (HR), 1.54), liver metastasis (HR, 1.21), dyspnea (HR, 1.35), edema (HR, 1.25), prognostic performance index (HR, 1.56), neutrophil-lymphocyte ratio (HR, 1.43), and GPS of 2 (HR, 1.36). The sensitivity and specificity for 3-week prognosis of a GPS of 2 were 0.879 and 0.410. Median survival time with GPS of 0, 1, and 2 was 58 days (95 % confidence interval, 48-81), 43 days (37-50), and 21 days (19-24), respectively (log-rank test, p < 0.001).The GPS was a good prognostic indicator for cancer patients in palliative settings.
2015Systemic changes following carrageenan-induced paw inflammation in rats.Inflamm ResCarrageenan-induced paw edema has been described as a local and acute inflammatory process. In fact, little is known about the time course and systemic changes following a carrageenan injection. In this study, we examine the systemic changes that follow carrageenan injection in the paw.Acute inflammation was produced by subplantar injection of carrageenan in a hind paw of Sprague-Dawley rats. Saline was used in control rats. Paw volume was measured with a plethysmometer. The hot plate latency test was used to quantify antinociception. C-reactive protein (CRP) levels were measured with a sandwich enzyme immunoassay. Fibrinogen concentration was measured using the gravimetric method. Lung morphometric analysis was performed using an image processing package. Lungs and paws were also examined for tissue factor (TF) and proinflammatory cytokines expression by immunohistochemistry.We found diverse systemic changes including increased levels of acute phase proteins, such as CRP and fibrinogen, and a lung inflammatory process characterized by lung edema, fibrin deposition, and leukocyte infiltration. An elevated expression of TF, IL-6, IL-1β, and TNFα, was observed in paw and lung tissue sections by immunohistochemical methods.This study provides new evidence that a local carrageenan injection induces a systemic response.
2015Adverse events of anti-tumor necrosis factor α therapy in ankylosing spondylitis.PLoS OneThis study aims to investigate the prevalence of short-term and long-term adverse events associated with tumor necrosis factor-α (TNF-α) blocker treatment in Chinese Han patients suffering from ankylosing spondylitis (AS).The study included 402 Chinese Han AS patients treated with TNF-α blockers. Baseline data was collected. All patients were monitored for adverse events 2 hours following administration. Long-term treatment was evaluated at 8, 12, 52 and 104 weeks follow-up for 172 patients treated with TNF-α blockers.Short-term adverse events occurred in 20.15% (81/402), including rash (3.5%; 14/402), pruritus (1.2%; 5/402), nausea (2.2%; 9/402), headache (0.7%; 3/402), skin allergies (4.0%; 16/402), fever (0.5%; 2/402), palpitations (3.0%; 12/402), dyspnea (0.5%; 2/402), chest pain (0.2%; 1/402), [corrected] abdominal pain (1.0%; 4/402), hypertension (2.2%; 9/402), papilledema (0.5%; 2/402), laryngeal edema (0.2%; 1/402) and premature ventricular contraction (0.2%; 1/402). Long-term adverse events occurred in 59 (34.3%; 59/172) patients, including pneumonia (7.6%; 13/172), urinary tract infections (9.9%; 17/172), otitis media (4.7%; 8/172), tuberculosis are (3.5%; 6/172) [corrected], abscess (1.2%; 2/172), oral candidiasis (0.6%; 1/172), elevation of transaminase (1.7%; 3/172), anemia (1.2%; 2/172), hematuresis (0.6%; 1/172), constipation (2.3%; 4/172), weight loss (0.6%; 1/172), exfoliative dermatitis (0.6%; 1/172). CRP, ESR and disease duration were found to be associated with an increased risk of immediate and long-term adverse events (P<0.05). Long-term treatment with Infliximab was associated with more adverse events than rhTNFR-Fc (P<0.01).This study reports on the prevalence of adverse events in short-term and long-term treatment with TNF-α blocker monotherapy in Chinese Han AS patients. Duration of disease, erythrocyte sedimentation rate, and c-reactive protein serum levels were found to be associated with increased adverse events with anti-TNF-α therapy. Long-term treatment with Infliximab was associated with more adverse events than rhTNFR-Fc.
2015Myelodysplastic syndrome precedes the onset of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome.Tohoku J Exp MedRemitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical synovitis predominantly involving the wrists, and is associated with marked pitting edema of the dorsum of the hands. Although the etiology of RS3PE syndrome is still unknown, several putative associations with malignancies and hematological disorders have been reported. Myelodysplastic syndrome (MDS) is characterized by infective hematopoiesis with possible transformation to leukemia; however, an association between RS3PE syndrome and MDS has been rarely reported. Here, we describe a 67-year-old man with MDS with refractory anemia who developed RS3PE syndrome 3 months after the diagnosis of MDS. The patient presented with polyarthritis with pitting edema at the dorsum of the hands, the elevated serum levels of C-reactive protein and a proinflammatory cytokine, interleukin-6, and the elevated plasma levels of vascular endothelial growth factor (VEGF). VEGF has been shown to be involved in the pathogenesis of RS3PE syndrome. Treatment with low doses of corticosteroids resulted in the regression of polyarthritis and pitting edema of the dorsum of the hands, as well as a reduction in the elevated levels of plasma VEGF. Partial resolution of refractory anemia was also observed with steroid therapy. In summary, RS3PE syndrome developed shortly after MDS was identified in this patient. The sequence of clinical events suggests that MDS-mediated immunological abnormalities including inflammatory cytokine induction may be responsible for the association between MDS and RS3PE syndrome. Patients with RS3PE syndrome should be screened for hematological disorders that promote proinflammatory mediators.
2016Systemic inflammatory response due to chloroform intoxication--an uncommon complication.Int J Legal MedWell-known adverse effects of chloroform are drowsiness, nausea, and liver damage. Two cases with an uncommon complication due to chloroform intoxication are presented. In the first case, a general physician, because of nausea and dyspnea, admitted a 34-year-old woman to hospital. She developed a toxic pulmonary edema requiring mechanical ventilation for a few days, and a systemic inflammatory response syndrome (SIRS) with elevated white blood cell counts, a moderate increase of C-reactive protein, and slightly elevated procalcitonin levels. There were inflammatory altered skin areas progressing to necrosis later on. However, bacteria could be detected neither in blood culture nor in urine. Traces of chloroform were determined from a blood sample, which was taken 8 h after admission. Later, the husband confessed to the police having injected her chloroform and put a kerchief soaked with chloroform over her nose and mouth. In the second case, a 50-year-old man ingested chloroform in a suicidal attempt. He was found unconscious in his house and referred to a hospital. In the following days, he developed SIRS without growth of bacteria in multiple blood cultures. He died several days after admission due to multi-organ failure. SIRS in response to chloroform is a rare but severe complication clinically mimicking bacterial-induced sepsis. The mechanisms leading to systemic inflammation after chloroform intoxication are currently unclear. Possibly, chloroform and/or its derivates may interact with pattern recognition receptors and activate the same pro-inflammatory mediators (cytokines, interleukins, prostaglandins, leukotrienes) that cause SIRS in bacterial sepsis.
2015Predictors of lower-extremity amputation in patients with an infected diabetic foot ulcer.Diabetes CareInfection commonly complicates diabetic foot ulcers and is associated with a poor outcome. In a cohort of individuals with an infected diabetic foot ulcer, we aimed to determine independent predictors of lower-extremity amputation and the predictive value for amputation of the International Working Group on the Diabetic Foot (IWGDF) classification system and to develop a risk score for predicting amputation.We prospectively studied 575 patients with an infected diabetic foot ulcer presenting to 1 of 14 diabetic foot clinics in 10 European countries.Among these patients, 159 (28%) underwent an amputation. Independent risk factors for amputation were as follows: periwound edema, foul smell, (non)purulent exudate, deep ulcer, positive probe-to-bone test, pretibial edema, fever, and elevated C-reactive protein. Increasing IWGDF severity of infection also independently predicted amputation. We developed a risk score for any amputation and for amputations excluding the lesser toes (including the variables sex, pain on palpation, periwound edema, ulcer size, ulcer depth, and peripheral arterial disease) that predicted amputation better than the IWGDF system (area under the ROC curves 0.80, 0.78, and 0.67, respectively).For individuals with an infected diabetic foot ulcer, we identified independent predictors of amputation, validated the prognostic value of the IWGDF classification system, and developed a new risk score for amputation that can be readily used in daily clinical practice. Our risk score may have better prognostic accuracy than the IWGDF system, the only currently available system, but our findings need to be validated in other cohorts.
Systemic inflammatory response during cardiac surgery: a pilot study.Innovations (Phila)There is a growing body of evidence indicating that perioperative fluid management during cardiac surgery influences patient care and outcome. The choice of fluid therapy and the degree of systemic inflammatory response triggered during surgery control the effects of tissue edema formation and end-organ function. As such, "goal-directed" fluid resuscitation protocols that measure colloid osmotic pressure (COP) may promote improvements in patient morbidity and mortality.Thirty patients scheduled for primary coronary artery bypass grafting were prospectively randomized for perioperative fluid treatment under COP guidance [albumin (ALB), n = 17] or conventional fluid protocols without COP support (control, n = 13). Whole-blood samples were drawn at four different time intervals including (A) anesthesia induction, (B) 10 minutes after the initiation of cardiopulmonary bypass, (C) at the completion of sternal skin approximation, and (D) 3 hours after admission to the cardiac intensive care unit. Interleukin 6 (IL-6) and IL-8 were measured by immunometric, enzyme-linked immunosorbent assays as well as C-reactive protein. Colloid osmotic pressure values were measured using a colloid osmometer.As compared with conventional fluid protocols, the patients treated in the intervention (ALB) group received significantly less total perioperative fluid [7893.6 (1874.5) vs 10,754.8 (2403.9), P = 0.001], and this relationship remained after controlling for age, sex, and The Society of Thoracic Surgeons risk score (β = -0.5, t = -3.1, P = 0.005). Colloid osmotic pressure values were significantly higher in the ALB group at time point D after surgery (P = 0.03). There were no significant differences in IL-6, IL-8, and C-reactive protein values between the groups at any of the time blood draw intervals. Perioperative outcomes were evaluated by treatment group. For both groups, the incidence of perioperative morbidity was low and did not differ by treatment group.The use of COP-guided fluid resuscitation was associated with a significant reduction in perioperative fluid demand. However, patients prescribed to COP-guided fluid therapy did not experience a reduction in whole-body inflammation or improved surgical outcome as compared with conventional fluid management techniques.
Evaluation of antinociceptive and antirheumatic activity of (L.) Poir. using experimental models.Ayu(L.) Poir. (Asteraceae), a popular Indian medicinal plant is traditionally used for rheumatism in the knee joint and pain in the muscles.To investigate antinociceptive and antirheumatic activity of (L.) Poir. using experimental models.Antinociceptive activity of methanolic extract of (L.) Poir. (GMME) (500 mg/kg, 1000 mg/kg, p.o.) was evaluated in rats using tail flick test. Anti-inflammatory and anti-arthritic activity of GMME (1000 mg/kg, p.o.) was evaluated using carrageenan-induced rat paw edema and complete Freund's adjuvant (CFA)- induced arthritis models. The degree of arthritis was evaluated by hind paw swelling, body weight changes, arthritic index, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and C-reactive protein (CRP) supported by histopathology of ankle joints.GMME treatment showed a significant increase in the latency for tail flick and provided significant protection against carrageenan-induced rat paw edema. 21 days treatment of GMME significantly inhibited paw edema found to be induced by arthritis by CFA in rats. Further, GMME treatment also reversed arthritic index and loss of body weight and reduced CFA-induced rise of ESR, RF, and CRP significantly in rats. Histopathological study of ankle joint revealed that GMME inhibited edema formation and cellular infiltration induced by CFA.GMME possesses antinociceptive, anti-inflammatory, and antirheumatic activities.
2015Inhibitory effect of Careya arborea on inflammatory biomarkers in carrageenan-induced inflammation.Pharm BiolCareya arborea Roxb. (Lecythidaceae) has multiple applications in traditional medicine; it exhibits analgesic, antibacterial, anti-inflammatory, antiulcer, and protective effects. However, the effect of C. arborea on biochemical and immmunological inflammatory mediators has not been explored.The present study investigates the anti-inflammatory potential of the methanol extract of C. arborea stem bark and further assesses its possible mechanism on the modulation of inflammatory biomarkers.Anti-inflammatory activity of C. arborea methanol extract (CAME) was evaluated (100 and 200 mg/kg, p.o) using indomethacin (10 mg/kg, p.o) as the standard drug in Wistar albino rats. Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left hind paw. The anti-inflammatory mechanism was studied by measuring malondialdehyde (MDA), C-reactive protein (CRP), nitric oxide (NO), myeloperoxidase (MPO), TNF-α, and IL-1β levels in both control and treated groups. A protocol has also been established to quantify quercetin and betulinic acid content in CAME using HPTLC fingerprint.Careya arborea significantly (p < 0.001) decreased carrageenan-induced paw edema, showed a reduction of 48.87 and 65.53% at doses of 100 and 200 mg/kg, respectively. Moreover, CAME significantly decreased the MDA, CRP, NO, and MPO levels, elevated by carrageenan induced inflammation. CAME also markedly down-regulated serum TNF-α and IL-1β levels. These findings were further supported by the histological study. The content of quercetin and betulinic acid in CAME was found to be 0.177 and 3.14%, respectively.Several mechanisms, including the inhibition of pro-inflammatory cytokines, enzymes and mediators release, appear to account for the anti-inflammatory potential of C. arborea.
2015Two cases of metallosis from metal-on-polyethylene total hips: an emerging problem.PM RThis report describes 2 cases of metallosis from metal-on-polyethylene total hip replacements. Case 1 involved a Stryker rejuvenate implant, which has since been recalled. This patient had minimal symptoms, an elevated cobalt level, and loosening. The patient in case 2 had a Dupuys Pinnacle system, with symptoms of weakness, rash, and hip pain. Abnormal laboratory values include elevated sedimentation rate, C-reactive protein, creatinine, cobalt, and decreased hematocrit. Magnetic resonance imaging revealed synovial thickening and extracapsular edema. Although metallosis is a well-established complication of metal-on-metal implants, emerging data reveal that it also may be a problem in non-metal-on-metal implants such as either metal-on-polyethylene or ceramic-on-polyethylene implants, perhaps related to modular corrosion.
2015Systemic and flap inflammatory response associates with thrombosis in flap venous crisis.InflammationVenous crisis represents the most common complication in flap surgery and often results in flap failure. The gold standard for free flap monitoring is frequent clinical examination. The current study examined the systemic inflammatory response during the immediate post-operative period following flap venous crisis. Superficial epigastric artery perforator flap transplantation was performed in a total of 30 rabbits. Fifteen animals received venous obstruction by vein ligation (venous crisis group, n = 15) and others were sham treated (control group, n = 15). Venous thrombosis was examined by immunohistochemistry staining. Plasma levels of inflammatory response markers (IL-6, IL-8, TNF-α, and C-reactive protein) and thrombosis biomarkers (von Willebrand factor and tissue factor) were measured at 0, 2, and 4 h post-operation by enzyme-linked immunosorbent assay. The mRNA levels of relevant biomarkers in the flap were analyzed with quantitative real-time PCR. Flap histopathological examination showed erythrocyte and neutrophil aggregations in venous lumen and erythrocyte diapedesis. At 8 h post-operation, serious edema and fibrinoid necrosis were observed and the venous lumen was almost blocked by thrombus. The venous crisis group had higher plasma levels of IL-8, TNF-α, and thrombosis biomarkers. Vein ligation also increased the mRNA levels of IL-8, TNF-α, C-reactive protein, von Willebrand factor, and tissue factor in the flap. No significant change in IL-6 levels was observed between the control group and the venous crisis group. Flap venous crisis was accompanied by the increase in a number of inflammatory and thrombosis markers, both in the peripheral blood and the flaps.
2015Local infliximab injection of sacroiliac joints in non-radiographic axial spondyloarthritis: Impact on clinical and magnetic resonance imaging parameters of disease activity.Mod RheumatolTo evaluate the effectiveness of infliximab (IFX) injection into sacroiliac joints (SIJs) of non-radiographic axial spondyloarthritis (nr-axial SpA) and its impact on clinical and MRI parameters of disease activity.Thirty-seven patients fulfilling the Association of Spondyloarthritis International Society (ASAS) criteria for axial SpA were initially studied, with disease duration not exceeding 1 year and failed to respond to non-steroidal anti-inflammatory drugs (NSAIDs). Only SpA having active sacroiliitis on MRI without spondylitis (number = 7) were selected to receive bilateral SIJ injection of 20 mg IFX. Follow-up MRI was done at 24 weeks post-injection. Patients were clinically evaluated before, and 12 and 24 weeks after SIJ injection. Evaluation included back pain and stiffness scores, and Bath Ankylosing Spondylitis (BAS) Disease indices and C-reactive protein (CRP) levels. ASAS response criteria were also assessed.Twelve and twenty-four weeks after injection, there was significant decrease in back pain, stiffness, and BAS Disease Activity and Global indices. BAS Functional index, CRP, and mean bone marrow edema score of SIJs were decreased without reaching statistical significance. All patients achieved ASAS20 and five (71.4%) achieved ASAS40.SIJ injection of IFX could be a therapeutic option in early nr-axial SpA who failed to respond to NSAIDs.
2014Anti-inflammatory effect of glycosaminoglycan derived from Gryllus bimaculatus (a type of cricket, insect) on adjuvant-treated chronic arthritis rat model.J Toxicol Environ Health AAnti-inflammatory effects of glycosaminoglycan (GAG) derived from cricket (Gryllus bimaculatus, Gb) were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritic rat model. This GAG produced a significant anti-edema effect as evidenced by inhibition of C-reactive protein (CRP) and rheumatoid factor, and interfered with atherogenesis by reducing proinflammatory cytokine levels of (1) vascular endothelial growth factor (VEGF) production in human umbilical vein endothelial cells (HUVEC), (2) interleukin-6, (3) prostaglandin E2-stimulated lipopolysaccharide in RAW 264.7 cells, and (4) tumor necrosis factor (TNF)-α production in normal splenocytes, in a dose-dependent manner. This GAG was also found to induce nitric oxide (NO) production in HUVEC cells and elevated endothelial nitric oxide synthase (eNOS) activity levels. Histological findings demonstrated the fifth lumbar vertebrae (LV) dorsal root ganglion, which was linked to the paw treated with Gb GAG, was repaired against CFA-induced cartilage destruction. Further, combined indomethacin (5 mg/kg)-Gb GAG (10 mg/kg) inhibited more effectively CFA-induced paw edema at 3 h and 2 or 3 d after treatment to levels comparable to only the anti-inflammatory drug indomethacin. Ultraviolet (UV)-irritated skin inflammation also downregulated nuclear factor κB (NFκB) activity in transfected HaCaT cells. Data suggest that the anti-inflammatory effects of GAG obtained from cricket (Gb) may be useful for treatment of inflammatory diseases including chronic arthritis.
2015Biomarkers for radiographic progression in rheumatoid arthritis.Curr Pharm DesTreatment of patients with rheumatoid arthritis (RA) is rarely personalized, since predictors of disease course are lacking. The severity of RA can be measured objectively by radiographic progression. The most reliable way to measure radiographic progression is in a longitudinal cohort with serial time points, scoring on a quantitative scale, with a validated scoring method and trained readers. Current models used to predict radiographic progression are based on C-reactive protein and anti-citrullinated protein antibodies. Other biomarkers could increase the prognostic ability of these models. In this review, we evaluated the published (and partly nonpublished) data on genetic, serologic, and imaging biomarkers for the severity of joint destruction in RA. We evaluated variants in 10 genes (CD40, IL2RA, IL4R, IL15, OPG, DKK1, SOST, GRZB, MMP9, and SPAG16). In 5 variants (IL2RA, DKK1, GRZB, MMP9, and SPAG16), we found evidence of an association at the functional level. We evaluated several serological biomarkers, namely, autoantibodies (RF, ACPA, anti-CarP), markers related to inflammation (ESR, CRP), and proteinases or components of the extracellular matrix of bone and cartilage (MMP3, CTX-I, CTX-II, COMP, TIMP1, PYD, RANKL/OPG, CXCL13). Finally, we evaluated markers that can be visualized by ultrasound or MRI, including erosions, bone marrow edema, synovitis, and tenosynovitis. Several studies showed that bone marrow edema and synovitis on MRI are robust predictors of radiographic progression. Some studies showed that inflammation detected with ultrasound predicted radiographic progression. Future studies will reveal whether adding and combining all these different biomarkers will increase the accuracy of risk models predicting radiographic progression in RA.
2014Case report: protein-losing enteropathy caused by Mesocestoides vogae (syn. M. corti) in a dog.Vet ParasitolAn eight-year-old, neutered, female Shetland Sheepdog presented with a 6-week history of small intestinal diarrhea. Regenerative anemia, hypoproteinemia, and an increased plasma C-reactive protein concentration were detected on blood examination. Fecal examination and abdominal radiography were unremarkable. Abdominal ultrasonography showed diffusely hyperechoic mucosa in the small intestine. Gastroduodenoscopy, performed under general anesthesia, revealed mucosal edema and increased granularity in the duodenum and jejunum. Histopathological examination of the endoscopically biopsied small intestinal mucosa revealed tapeworm infection. A single administration of a combined anthelmintic drug (5mg/kg praziquantel, 14.4 mg/kg pyrantel pamoate, and 15 mg/kg febantel) was successful for deworming, and the dog fully recovered. The parasites were removed from stored frozen duodenal mucosa and morphologically identified as Mesocestoides sp. immature adult worms. Mitochondrial (mt) 12S rDNA and mt cytochrome c oxide subunit 1 genes were amplified from the parasites. DNA sequence analysis showed that the genes shared 100% identity with those of reported M. vogae (syn. M. corti). This is the first reported case of protein-losing enteropathy caused by M. vogae in a dog.
2016Ultrasonography and magnetic resonance imaging findings of rheumatoid arthritis-like arthritis in a patient with adult T-cell leukemia.Mod RheumatolA 43-year-old Japanese woman with adult T-cell leukemia (ATL) developed rheumatoid arthritis-like polyarthritis with dermatitis and skin erosion. Her rheumatoid factor and C-reactive protein results were positive. Musculoskeletal ultrasonography showed intra-articular and peritendinous power Doppler signal-positive synovitis. Plain magnetic resonance imaging showed synovitis of the above lesion and remarkable bone marrow edema/osteitis. She was diagnosed as having ATL-associated arthritis based on the invasion of ATL cells by skin biopsy at the arthritis lesion.
2014Therapeutic efficacy of vitamin E δ-tocotrienol in collagen-induced rat model of arthritis.Biomed Res IntRheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease primarily involving inflammation of the joints. Although the management of the disease has advanced significantly in the past three decades, there is still no cure for RA. The aim of this study was to determine the therapeutic efficacy of δ-tocotrienol, in the rat model of collagen-induced arthritis (CIA). Arthritis was induced by intradermal injection of collagen type II emulsified in complete Freund's adjuvant. CIA rats were orally treated with δ-tocotrienol (10 mg/kg) or glucosamine hydrochloride (300 mg/kg) from day 25 to 50. Efficacy was assessed based on the ability to reduce paw edema, histopathological changes, suppression of collagen-specific T-cells, and a reduction in C-reactive protein (CRP) levels. It was established that δ-tocotrienol had the most significant impact in lowering paw edema when compared to glucosamine treatment. Paw edema changes correlated well with histopathological analysis where there was a significant reversal of changes in groups treated with δ-tocotrienol. The results suggest that δ-tocotrienol is efficient in amelioration of collagen-induced arthritis. Vitamin E delta-tocotrienol may be of therapeutic value against rheumatoid arthritis.
2014Crohn's disease successfully treated with infliximab in a patient receiving hemodialysis: case report and review of the literature.Medicine (Baltimore)There is limited information in the use of antitumor necrosis factor α, infliximab, in patients on hemodialysis. In Crohn's disease (CD), only 3 cases are reported.A 76-year-old man on hemodialysis for renal failure caused by immunoglobulin A nephropathy developed diarrhea and abdominal pains. A marked edema was observed in the pretibia and ankle. An increase of C-reactive protein (CRP) and erythrocyte sedimentation rate, hypoalbuminemia, hypocholesterolemia, and moderate anemia was found. Ultrasonography and computed tomography (CT) found wall thickness in the left colon. Sigmoidoscopy revealed multiple ulcers in the sigmoid colon and noncaseating epithelioid granuloma was found in the biopsy specimen. Barium enema study exhibited collar button signs and longitudinal ulcers in the left colon.A severe form of CD was diagnosed. Metronidazole seemed to decrease CRP but was ineffective in ameliorating diarrhea. Infliximab rather than steroid hormone was chosen for the treatment. Standard induction therapy with infliximab was initiated. Symptoms rapidly improved then disappeared. CD activity index decreased from 747 to a remission level of 134 after 2 infusions of infliximab. Scheduled maintenance infliximab therapy was administered after the induction therapy. Ultrasonography and CT showed a disappearance of the wall thickness of the colon. Adverse reactions were not observed.Infliximab was effective and safe in a patient with CD on hemodialysis. Our case has added additional literature in accordance with previous reports supporting infliximab as effective and safe in patients on hemodialysis.
2014Relationship between uncommon computed tomography findings and clinical aspects in patients with acute pyelonephritis.Korean J UrolComputed tomography (CT) has become popular in the diagnosis of acute pyelonephritis (APN) and its related complications in adults. The aim of this study was to investigate the relationship between uncommon CT findings and clinical and laboratory data in patients with APN.From July 2009 to July 2012, CT findings and clinical data were collected from 125 female patients with APN. The six uncommon CT findings (excluding a wedge-shaped area of hypoperfusion in the renal parenchyma) studied were perirenal fat infiltration, ureteral wall edema, renal abscess formation, pelvic ascites, periportal edema, and renal scarring. The clinical parameters analyzed were the age and body mass index of the patients as well as the degree and duration of fever. Laboratory parameters related to inflammation and infection included white blood cell count, C-reactive protein (CRP) level, erythrocyte sedimentation rate, pyuria, and bacteriuria.The most common CT finding was perirenal fat infiltration (69 cases, 55%). A longer duration of fever, higher CRP level, and grade of pyuria were related with perirenal fat infiltration (p=0.010, p=0.003, and p=0.049, respectively). The CRP level was significantly higher in patients with renal abscess and ureteral wall edema (p=0.005 and p=0.015, respectively).The uncommon CT findings that were related to aggravated clinical and laboratory parameters of APN patients were perirenal fat infiltration, ureteral wall edema, and renal abscess formation. The inflammatory reaction and tissue destruction may be more aggressive in patients with these CT findings.
2014Nutritional parameters are associated with mortality in acute kidney injury.Clinics (Sao Paulo)The objective of this study was to perform a nutritional assessment of acute kidney injury patients and to identify the relationship between nutritional markers and outcomes.This was a prospective and observational study. Patients who were hospitalized at the Hospital of Botucatu School of Medicine were evaluated between January 2009 and December 2011. We evaluated a total of 133 patients with a clinical diagnosis of acute kidney injury and a clinical presentation suggestive of acute tubular necrosis. We explored the associations between clinical, laboratory and nutritional markers and in-hospital mortality. Multivariable logistic regression was used to adjust for confounding and selection bias.Non-survivor patients were older (67 ± 14 vs. 59 ± 16 years) and exhibited a higher prevalence of sepsis (57.1 vs. 21.4%) and higher Acute Tubular Necrosis-Individual Severity Scores (0.60 ± 0.22 vs. 0.41 ± 0.21) than did survivor patients. Based on the multivariable analysis, laboratorial parameters such as blood urea nitrogen and C-reactive protein were associated with a higher risk of death (OR: 1.013, p=0.0052; OR: 1.050, p=0.01, respectively), and nutritional parameters such as low calorie intake, higher levels of edema, lower resistance based on bioelectrical impedance analysis and a more negative nitrogen balance were significantly associated with a higher risk of death (OR: 0.950, p=0.01; OR: 1.138, p=0.03; OR: 0.995, p=0.03; OR: 0.934, p=0.04, respectively).In acute kidney injury patients, a nutritional assessment seems to identify nutritional markers that are associated with outcome. In this study, a low caloric intake, higher C-reactive protein levels, the presence of edema, a lower resistance measured during a bioelectrical impedance analysis and a lower nitrogen balance were significantly associated with risk of death in acute kidney injury patients.
2014Cerebral neurocysticercosis mimicking or comorbid with episodic migraine?BMC NeurolNeurocysticercosis is a major cause of neurological symptoms in developing countries. We report a case of cerebral neurocysticercosis presenting as episodic migraine without aura, with clinico-radiological correlations and discuss the possible causal influence of neurocysticercosis on the pathomechanisms of migraine.We report a 24 year-old male consulting for a one year history of recurrent headaches. He described bilateral frontal and/or temporal attacks of throbbing headache, moderate to severe in intensity, worsened by head movements and accompanied by nausea, photophobia and phonophobia. Attacks lasted between 12 and 60 hours if untreated. He never had symptoms suggestive of a migraine aura or an epileptic seizure. Headache attacks progressively increased in frequency to up to 5 to 7 severe attacks per month. On taking history, the patient reported having consumed undercooked porcine meat. Physical examination was unremarkable. A brain CT scan showed two contiguous occipital cystic lesions with ring enhancement and surrounding edema suggestive of cerebral neurocysticercosis. On laboratory work-up, blood serology for cysticercal antibodies was positive. Full blood count, erythrocyte sedimentation rate, c - reactive protein level, human immunodeficiency virus serology, liver and hepatic function were all normal. Albendazole (1000 mg/day) and prednisolone (60 mg/day) were prescribed for seven days. The patient was examined again two and six months after the end of his treatment and there was a significant reduction in headache severity and frequency.We propose that in our patient the occipital neurocysticercosis lesions cause migraine without aura-like attacks via inflammation in the surrounding brain parenchyma leading to sensitization of the trigemino-vascular system. We cannot rule out, however, the possibility that our patient has a genetic predisposition for migraine without aura and that the fortuitous association of neurocysticercosis is simply an aggravating factor of his migraine.
2014Usefulness of the endotoxin activity assay to evaluate the degree of lung injury.Yonsei Med JIt has been reported that the Pulse Contour Cardiac Output (PiCCO) is very useful mainly in the field of intensive care and treatment to grasp the pathophysiological conditions of pulmonary edema because of its capability of obtaining data such as Pulmonary Vascular Permeability Index (PVPI) and Extra Vascular Lung Water (EVLW). Furthermore, a high degree of usability of various markers has been reported for better understanding of the pathological conditions in cases with septicemia.The correlation between the cardiorespiratory status based upon the PiCCO monitor (EVLW and PVPI) and inflammatory markers including C reactive protein, procalcitonin (PC), and Endotoxin Activity Assay (EAA) were evaluated in 11 severe cases that required treatment with a respirator in an intensive care unit.The EAA values were significantly higher in patients with abnormal EVLW at 0.46±0.20 compared to the normal EVLW group at 0.21±0.19 (p=0.0064). In a similar fashion, patients with abnormal PVPI values tended to have higher PC levels at 18.9±21.8 compared to normal PVPI cases at 2.4±2.2 (p=0.0676). On the other hand, PVPI was significantly higher in the abnormal EAA group at 3.55±0.48 in comparison with the normal EAA group at 1.99±0.68 (p=0.0029). The abnormal EAA group tended to have higher PVPI values than the normal EAA group.The EAA is a measurement method designed to estimate the activity of endotoxins in the whole blood. Our results suggest that the EAA value, which had the greatest correlation with lung disorders diagnosed by the PiCCO monitoring, reflects inflammatory reactions predominantly in the lungs.
2013The effect of experimental streptococcus infection in myocarditis on some biochemical and inflammatory markers in albino rats.Afr Health SciMyocarditis is an uncommon disease that presents with a wide range of symptoms in children and adults. It is histologically characterized by varying degrees of myocardialnecrosis, edema and cellular infiltration myocardial inflammation is a nonspecificresponse to many triggers such as bacterial infection, cardio toxic agents, ormechanical injury.This study was carried out to investigate the experimental Streptococcus faecalis induction of myocarditis and its effect on some blood parameters, inflammatory markers and histopathological changes in male albino rats.Rats were infected by intraperitoneal injection of 10 8 CFU/ml of Streptococcus faecalis and sacrificed after one, two and seven days post infection. Biochemical analyses of blood were carried out to investigate the serum biomarkers of inflammation, liver function tests, cardiac enzymes & kidney function tests.All biochemical analyses showed statistically significant increase in the measured parameters due to bacterial infections except for blood urea which appear to be normal. A significant positive correlation was observed between lactate dehydrogenase enzyme (LDH) with creatinine (r =0.778, P<0.01). In the 7 days group, there were significant positive correlations between aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (r=0.675, P<0.05), erythrocyte sedimentation rate (ESR) with Urea (r=0.659, P<0.05) and alkaline phosphatase (ALP) with C-reactive protein (CRP) (r=0.765, p<0.01).Many of these biomarkers will provide important new insights into pathophysiology and aid in the diagnosis and management of cardiovascular patients.
2014A Case of Membranous Glomerulonephropathy Associated with Takayasu's Arteritis.Case Rep Nephrol UrolGlomerulonephropathy is a rare complication of Takayasu's arteritis (TA). To date, most glomerulonephropathies associated with TA show the histological feature of mesangial proliferation. Membranous glomerulonephropathy (MG) is a form of glomerulonephropathy in which the mesangial proliferation is not conspicuous and its association with TA is extremely rare. A 54-year-old man was referred to our hospital due to progressive edema in the lower limbs and nephrotic range proteinuria. Five years previously, he underwent percutaneous angioplasty for left subclavian artery stenosis. Kidney biopsy revealed stage II MG. General examination including enhanced CT scan confirmed the presence of TA. He started oral prednisolone therapy at a dose of 40 mg daily. The C-reactive protein level normalized 7 days after the prednisolone therapy. Three months later, proteinuria had remitted. Though the true relationship between MG and TA was not revealed in present case, considering the fact that complete remission of nephrotic syndrome occurred following the improvement of C-reactive protein level in response to steroid therapy, TA might be the secondary cause of MG. To our best knowledge, only two case reports described the association of MG and TA previously. Those two patients, however, also demonstrated the feature of systemic lupus erythematosus in addition to TA. This is the first case report that describes a patient who presented as MG associated with TA, but not complicated by systemic lupus erythematosus.
2014Impact of clipping versus coiling on postoperative hemodynamics and pulmonary edema after subarachnoid hemorrhage.Biomed Res IntVolume management is critical for assessment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). This multicenter prospective cohort study compared the impact of surgical clipping versus endovascular coiling on postoperative hemodynamics and pulmonary edema in patients with SAH. Hemodynamic parameters were measured for 14 days using a transpulmonary thermodilution system. The study included 202 patients, including 160 who underwent clipping and 42 who underwent coiling. There were no differences in global ejection fraction (GEF), cardiac index, systemic vascular resistance index, or global end-diastolic volume index between the clipping and coiling groups in the early period. However, extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were significantly higher in the clipping group in the vasospasm period. Postoperative C-reactive protein (CRP) level was higher in the clipping group and was significantly correlated with postoperative brain natriuretic peptide level. Multivariate analysis found that PVPI and GEF were independently associated with high EVLWI in the early period, suggesting cardiogenic edema, and that CRP and PVPI, but not GEF, were independently associated with high EVLWI in the vasospasm period, suggesting noncardiogenic edema. In conclusion, clipping affects postoperative CRP level and may thereby increase noncardiogenic pulmonary edema in the vasospasm period. His trial is registered with University Hospital Medical Information Network UMIN000003794.
2014Development and validation of modified disease activity scores in rheumatoid arthritis: superior correlation with magnetic resonance imaging-detected synovitis and radiographic progression.Arthritis RheumatolTo develop and validate composite disease activity scores, based on widely available clinical measures, that would demonstrate improved correlation with detection of synovitis on magnetic resonance imaging (MRI) and radiographic progression, in comparison with conventional measures, in patients with rheumatoid arthritis (RA).This study was conducted as a secondary study of 2 RA clinical trials, GO-BEFORE (development cohort) and GO-FORWARD (validation cohort). Generalized estimating equations were used to evaluate independent cross-sectional associations of component variables (from all time points) with concurrent MRI measures of synovitis and bone edema in the development cohort. Based on regression coefficients, modified versions of the Disease Activity Score in 28 joints (M-DAS28), Simplified Disease Activity Index (M-SDAI), and Clinical Disease Activity Index (M-CDAI) were generated for each subject in the validation cohort. The M-DAS28, M-SDAI, and M-CDAI scores were compared to conventional scores of disease activity with regard to associations with MRI measures of synovitis and radiographic progression, assessed using Pearson's and Spearman's correlations, linear/logistic regression, and receiver operating characteristic analysis.Four variables were independently associated with MRI-detected synovitis and bone edema in the development cohort: C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), swollen joint count in 28 joints (SJC28), and evaluator's global assessment of disease activity using a visual analog scale (EvGA score). Modified disease activity scores were generated using the regression coefficients obtained in the synovitis models for all subjects in the validation cohort; modified scores were calculated as M-DAS28 = 0.49 × ln(CRP) + 0.15 × SJC28 + 0.22 × EvGA + 1 and M-SDAI = CRP + SJC28 + EvGA. Both modified and conventional disease activity scores correlated significantly with MRI measures of synovitis. Modified scores showed superior correlation with synovitis, as compared to conventional scores, at all time points (P < 0.05). Furthermore, the M-DAS28 and M-SDAI had superior test characteristics for prediction of radiographic progression at 52 weeks (both P < 0.05).Modified disease activity scores demonstrated superior correlation with MRI detection of synovitis at all time points, and more accurately predicted radiographic progression in patients with RA in a clinical trial setting.
2014Possible potentiation by certain antioxidants of the anti-inflammatory effects of diclofenac in rats.ScientificWorldJournalIn the present study, we investigated the potential beneficial impact of the addition of antioxidant supplements to diclofenac regimen in a model of carrageenan-induced paw. Rats were treated daily with antioxidants, that is, a-lipoic acid (50 mg/kg), selenium (2.5 mg/kg), vitamin C (1 g/kg), vitamin E (300 mg/kg), or zinc (25 mg/kg) on seven successive days and then received a single treatment with diclofenac or saline before carrageenan was injected to induce paw inflammation. The results indicated that these combinations did not significantly affect the percentage inhibition of paw edema caused by diclofenac alone; however, some combination treatments ameliorated signs of concomitant oxidative stress (such as alterations in plasma malondialdehyde (MDA) levels, hemolysate reduced glutathione levels, and erythrocytic superoxide dismutase enzyme activities) imparted by diclofenac alone. In some cases, few tested antioxidants in combination with diclofenac resulted in increased plasma levels of interleukin- (IL-) 6 and C-reactive protein (CRP). In conclusion, the results of these studies suggested to us that the added presence of natural antioxidants could be beneficial as standard anti-inflammatory therapeutics for a patient under diclofenac treatment, albeit that these effects do not appear to significantly build upon those that could be obtained from this common anti-inflammatory agent per se.
2014Disseminated Rhodococcus equi infection in a patient with Hodgkin lymphoma.Vojnosanit PreglRhodococcus (R) equi is an opportunistic, uncommon human pathogen that causes mainly infection in immunocompromised hosts. The disease is usually presented as subacute pneumonia that is mostly cavitary and sometimes bacteremic.We reported the extremly rare case of a 43-year-old woman with Hodgkin lymphoma, who developed R equi pulmonary infection after recieving multiple courses of chemotherapy. Secondary, the patient developed bacteremia, leading to sepsis and dissemination of R equi infection in many extrapulmonary sites. At addmission the patient was febrile, tachypnoic, tachycardic, hypotensive, with fa cial edema, splenomegaly, positive meningeal signs, left hemiparesis and paraparesis. Laboratory data included erythrocyte sedimentation rate (ESR) > 140 mm/h, C-reactive protein (CRP) 143.0 mg/L, red blood cells (RBC) 2.14 x 10(12)/L, whyite blood cells (WBC) 2.8 x 10(9)/L, lactate dehydrogenase (LDH) 706 U/L, serum albumin 26 g/L, sodium 127 mmol/L and potassium 2.7 mmol/L. Blood culture and culture of sputum and empyema were positive for R equi. Imaging studies demonstrated a large right cavitary pneumonia and abscess, empyema, pericarditis, mediastinal and intra-abdominal lymphadenopathy, brain and psoas abscesses, osteomyelitis and spondylodiscitis. The patient recovered completely after a 12-month treatment with combinations of parenteral and oral antibiotics (meropenem, vancomycin, teicoplanin, ciprofloxacin, rifampicin, macrolides etc), including drainage of abscesses and empyema. Eight years after completition of the treatment the patient was without recurrence of R equi infection and lymphoma.Since the eradication od R equi is very difficult, it is very important to make the diagnosis and initiate appropriate antibiotic therapy as soon as possible.
Immunomodulatory and protective properties of tacrolimus in experimental scorpion envenomation.Int J Immunopathol PharmacolInvolvement of imbalance between pro- and anti-inflammatory events has been reported in the developed pathogenesis after scorpion envenomation. The immunosuppressive and anti-inflammatory properties of tacrolimus (FK-506) have been investigated: i) to better understand evolution of signaling pathways which are involved in the immune system ii) to reduce observed clinical signs while keeping a balance between pro- and anti-inflammatory cytokines. Naval Medical Research Institute (NMRI) mice received tacrolimus (1 mg/kg every 12 hours per os) for 21 days before envenomation with a sublethal dose (10 microg/20 g body weight) of Androctonus australis hector venom (Aah). Cell migration, pulmonary edema, exudation, Myeloperoxydase (MPO), Eosinophil peroxydase (EPO), C-reactive protein (CRP), C3, Creatine phosphokinase (CPK), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and hyperglycemia were analyzed 30 min, 3 and 24 hours after injection of Aah venom. Histological analysis of lung parenchyma was undertaken 24 hours after envenomation. Aah lethality was evaluated on mice with or without pretreatment with tacrolimus. (Fab’)2 fragments (40 mg/kg) were also used as specific treatment in all protocols. Tacrolimus significantly inhibited cell migration, pulmonary edema, exudation, CRP and hyperglycemia. It also decreased MPO and EPO activities and prevented tissue damage in lung tissue, balancing seric parameter levels (CPK, ASAT and ALAT). The pretreated animals seemed to be protected by this macrolide against the venom lethality. These findings suggest that the overactivation of the immune system is one of the causes involved in the aggravation of the pathophysiological effects induced after envenomation. The obtained results showed that the use of F(ab’)2 fragments as specific treatment cannot reduce the induced inflammatory response.
2014Polyphenolics isolated from virgin coconut oil inhibits adjuvant induced arthritis in rats through antioxidant and anti-inflammatory action.Int ImmunopharmacolWe evaluated the protective efficacy of the polyphenolic fraction from virgin coconut oil (PV) against adjuvant induced arthritic rats. Arthritis was induced by intradermal injection of complete Freund's adjuvant. The activities of inflammatory, antioxidant enzymes and lipid peroxidation were estimated. PV showed high percentage of edema inhibition at a dose of 80mg/kg on 21st day of adjuvant arthritis and is non toxic. The expression of inflammatory genes such as COX-2, iNOS, TNF-α and IL-6 and the concentration of thiobarbituric acid reactive substance were decreased by treatment with PV. Antioxidant enzymes were increased and on treatment with PV. The increased level of total WBC count and C-reactive protein in the arthritic animals was reduced in PV treated rats. Synovial cytology showed that inflammatory cells and reactive mesothelial cells were suppressed by PV. Histopathology of paw tissue showed less edema formation and cellular infiltration on supplementation with PV. Thus the results demonstrated the potential beneficiary effect of PV on adjuvant induced arthritis in rats and the mechanism behind this action is due to its antioxidant and anti-inflammatory effects.
2014An elderly woman with peripheral spondyloarthritis with aortitis.Mod RheumatolA 75-year-old woman was admitted to our department because of backache and multiple joint pain. Serum C-reactive protein (CRP) level was 6.8 mg/dL, and serum rheumatoid factor and anti-citrullinated peptide antibody were negative. Magnetic resonance imaging (MRI) showed bone edema and synovitis of the sacroiliac joints. (18)Fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) showed increased uptakes in the bilateral elbow, shoulder, sternoclavicular, hip, and sacroiliac joints. In addition, increased uptakes were also observed in the bilateral cervical and subclavian arteries, and the thoracic aorta. Moreover, inflammation of the vascular walls and an aneurism in the right subclavian artery were observed on MRI. The patient's HLA type was HLA-B48 and B60. According to the Assessment of Spondyloarthritis (ASAS) classification criteria, peripheral spondyloarthropathy (SpA) was also diagnosed. Although the diagnostic criteria of Takayasu aortitis or giant cell aortitis were not fulfilled, we thought that active aortitis was also involved, and high-dose prednisolone was started. The patient's symptoms were diminished immediately, and CRP levels returned to normal. Although the etiology of the aortitis was not certain, this is the first report of late-onset peripheral SpA with aortitis, diagnosed by (18)FDG-PET and MRI. We recommended that it is important to evaluate the aortic involvement in late-onset SpA patients, when elevated systemic inflammation is observed.
2014An 8-month-old boy with purpuric skin lesions. Acute hemorrhagic edema of infancy.Pediatr AnnA previously healthy 8-month-old Hispanic boy presented with a 5-day history of an erythematous, non-pruritic papular eruption on both legs. The eruption was initially diagnosed as impetigo by his primary care practitioner but progressed despite trimethoprim / sulfamethoxazole therapy, with extension to the face, trunk, and all extremities. When the patient subsequently developed a fever of 100.8° F, emesis, diarrhea, and upper respiratory symptoms, he was referred to the pediatric dermatology clinic for evaluation. Further questioning revealed a 3-day febrile illness 6 weeks prior to presentation that was treated with ceftriaxone. Review of systems failed to identify any hematuria, blood in stool, or abdominal pain, but the parents did report swelling of the extremities and face, as well as decreased oral intake. On examination, the infant was in no apparent distress, afebrile, and had mild rhinorrhea. His mucous membranes were unaffected, and no lymphadenopathy or hepatosplenomegaly was noted. Cutaneous exam revealed numerous edematous erythematous to violaceous plaques on the cheeks, arms, buttocks, and legs with minimal involvement of the trunk. Several lesions on the arms had a distinct cockade (rosette or iris-like) pattern. There were no vesicles, bullae, or necrosis. Edema of the bilateral lower extremities was noted. Laboratory work up revealed a normal complete blood count (CBC), comprehensive metabolic panel, creatinine, and urinalysis. Platelets were borderline elevated at 439 TH/μL (140-440 TH/μL), and erythrocyte sedimentation rate and C-reactive protein (CRP) were minimally elevated at 22 mm (0-15 mm) and 3.1 mg/dL (0.0-0.99 mg/dL), respectively.
2014Combined use of high-sensitivity C-reactive protein and N-terminal pro-B-type natriuretic peptide for risk stratification of vascular surgery patients.Ann Vasc SurgWe sought to assess whether high-sensitivity C-reactive protein (hs-CRP) and pro-B-type natriuretic peptide (NT-proBNP) improve risk prediction when added to an established predictive tool and develop a point-based risk score.Four hundred eleven vascular surgery patients were enrolled. The primary outcome was a composite of death, acute coronary syndromes, pulmonary edema within 30 days of surgery, and postoperative troponin-I elevation. The risk score was developed from a logistic regression model by using an integer-based scoring system.The rate of the primary outcome was 18%. Adding both hs-CRP and NT-proBNP to the Revised Cardiac Risk Index led to an increase in C statistic from 0.670 to 0.774. The net reclassification improvement was 0.210 (P = 0.004) and the integrated discrimination improvement was 0.112 (P = 0.0001). In the multivariable regression analysis used to develop the risk score, insulin therapy for diabetes (odds ratio [OR]: 2.8; P = 0.003), open surgery (OR: 1.95; P = 0.027), fibrinogen >377 mg/dL (OR: 2.83; P = 0.001), hs-CRP >3.2 mg/L (OR: 3.85; P < 0.0001), and NT-proBNP >221 ng/L (OR: 4.05; P < 0.0001) were associated with the primary outcome. There was no statistical evidence of overfit. The C index was 0.82 and the Hosmer-Lemeshow statistic was 1.61 (P = 0.0447). The observed and predicted rates of the primary outcome across quartiles of risk score were highly correlated.Hs-CRP and NT-proBNP substantially improve risk prediction when added to an established predictive tool. The biochemical marker-based risk score may be useful for accurately risk-stratifying vascular surgery patients; nonetheless, further validation studies on external datasets are needed before it can be used in clinical practice.
2013Orbital cellulitis presenting as a first sign of incomplete kawasaki disease.Case Rep OphthalmolA 6-year-old boy was referred to our hospital with orbital cellulitis. He had a history of 7 days of fever despite antibiotherapy. At first, he only had pharyngitis and conjunctivitis, but then an orbital mass evolved which restricted the movement of his right eye and there was also periorbital inflammation resembling orbital cellulitis. Examination at presentation revealed conjunctivitis with secretion, periocular inflammation and edema, right-preauricular lymphadenopathy and restriction of upgaze in the right eye. Laboratory findings included a white blood cell count of 19,000 cells per mm3, with 81.5% neutrophils, 15.0% lymphocytes, 1.2% monocytes and 0.4% basophils. The erythrocyte sedimentation rate was 52 mm/h and the C-reactive protein level was 46.3 mg/dl. Magnetic resonance imaging confirmed orbital cellulitis and pansinusitis. Vancomycin (60 mg/kg/day) and meropenem (100 mg/kg/day) were administered, but desquamation on his fingertips and a rash appeared on the tenth day. A pediatric consultation resulted in a diagnosis of incomplete Kawasaki disease (KD). After administration of aspirin, the orbital inflammation regressed in 3 days. No coronary artery lesions were detected on the first echocardiography, but these did appear 6 weeks later. This confirmed the KD diagnosis.
2014Impact of intraoperative temperature and humidity on healing of intestinal anastomoses.Int J Colorectal DisClinical data indicate that laparoscopic surgery has a beneficial effect on intestinal wound healing and is associated with a lower incidence of anastomotic leakage. This observation is based on weak evidence, and little is known about the impact of intraoperative parameters during laparoscopic surgery, e.g., temperature and humidity.A small-bowel anastomosis was formed in rats inside an incubator, in an environment of stable humidity and temperature. Three groups of ten Wistar rats were operated: a control group (G1) in an open surgical environment and two groups (G2 and G3) in the incubator at a humidity of 60 % and a temperature of 30 and 37 °C (G2 and G3, respectively). After 4 days, bursting pressure and hydroxyproline concentration of the anastomosis were analyzed. The tissue was histologically examined. Serum levels of C-reactive-protein (CRP) were measured.No significant changes were seen in the evaluation of anastomotic stability. Bursting pressure was very similar among the groups. Hydroxyproline concentration in G3 (36.3 μg/g) was lower by trend (p = 0.072) than in G1 (51.7 μg/g) and G2 (46.4 μg/g). The histological evaluation showed similar results regarding necrosis, inflammatory cells, edema, and epithelization for all groups. G3 (2.56) showed a distinctly worse score for submucosal bridging (p = 0.061) than G1 (1.68). A highly significant increase (p = 0.008) in CRP was detected in G3 (598.96 ng/ml) compared to G1 (439.49 ng/ml) and G2 (460 ng/ml).A combination of high temperature and humidity during surgery induces an increased systemic inflammatory response and seems to be attenuating the early regeneration process in the anastomotic tissue.
2014A fast and effective method to assess myocardial hyperemia in acute myocarditis by magnetic resonance.Int J Cardiovasc ImagingCurrent cardiac magnetic resonance (CMR) quantitative signs for the diagnosis of myocarditis include myocardial edema, fibrosis and myocardial hyperemia (Hyp). Methods for the assessment of Hyp are actually complex and time-consuming. To test a simple and fast method to assess Hyp, using contrast enhancement steady state free precession (ceSSFP) technique. CMR imaging at 1.5T was performed on 39 patients with diagnosis of acute myocarditis and in 20 healthy controls. Hyp was evaluated in systolic and diastolic frames (Hyp-SYS and Hyp-DIA) as areas of myocardial hyperintensity in ceSSFP images early after gadolinium injection. Myocardial edema was evaluated using T2-STIR images. Myocardial fibrosis was assessed in conventional late gadolinium enhancement (LGE) images. A value of ≤12.1 g of Hyp-DIA was obtained as cut-off of normality in healthy controls. Using this threshold, Hyp was detected in 30 patients (77 %) with myocarditis. LGE was detected in 36 patients (92 %), and myocardial edema in 38 (97 %) patients with myocarditis A linear relation was found between Hyp-DIA and the extent of myocardial edema (R(2) 0.48, 95 % CI 0.47-0.85, p < 0.001) and the extent of LGE (R(2) 0.41, 95 % CI 0.31-0.61, p < 0.001). Patients with hyperemia had higher levels of C-reactive protein (p < 0.001), a higher extent of LGE (p < 0.05) and a larger left atrial area (p < 0.05). ceSSFP sequence at CMR is a novel and fast method to assess myocardial hyperemia in patient with acute myocarditis. Compared with non-Hyp subjects, patients with Hyp had more signs of inflammation and myocardial damage.
2014Exclusive enteral nutritional therapy can relieve inflammatory bowel stricture in Crohn's disease.J Clin GastroenterolTo examine the efficiency of exclusive enteral nutrition (EEN) in relieving inflammatory bowel stricture in patients with Crohn's disease (CD).Patients with CD usually develop bowel strictures due to transmural edema of intestinal wall, which can potentially be managed with conservative medical treatment. Previous studies showed that EEN therapy could induce clinical remission through its anti-inflammation effect.We achieved a prospective observational study. CD patients with inflammatory bowel stricture were preliminarily differentiated from a fibrous one, and further treated with EEN therapy for 12 weeks. Demographics and clinical variables were recorded. Nutritional (body mass index, albumin, pre-albumin, transferrin, etc.), inflammatory (C-reactive protein, erythrocyte sedimentation rate, white blood cell, etc.), and radiologic parameters (bowel wall thickness, luminal diameter, and luminal cross-sectional area) were evaluated at baseline, week 4, and week 12, respectively.Between May 2012 and January 2013, 65 patients with CD were preliminarily diagnosed with inflammatory bowel stricture and 6 patients were further excluded. Among the remaining 59 cases, 50 patients (84.7%) finished the whole EEN treatment, whereas the other 9 patients (15.3%) gained progressive bowel obstruction resulting in surgery. Intention-to-treat analyses showed that 48 patients (81.4%) achieved symptomatic remission, 35 patients (53.8%) achieved radiologic remission, and 42 patients (64.6%) achieved clinical remission. Among those patients who complete the whole EEN therapy, inflammatory, nutritional, and radiologic parameters improved significantly compared with baseline. Of note, the average luminal cross-sectional area at the site of stricture increased approximately 331% at week 12 (195.7 ± 18.79 vs. 59.09 ± 10.64 mm, P<0.001).EEN therapy can effectively relieve inflammatory bowel stricture in CD, which replenishes roles of enteral nutrition in the treatment of CD. Further studies are expected to investigate the underlying mechanisms of this effect in the future.
2013[A clinical analysis of 509 cases of sacroiliitis].Zhonghua Nei Ke Za ZhiTo study the clinical features of sacroiliitis and differential diagnosis.Totally 509 patients with chief complaints of back pain and diagnosed as sacroiliitis from January 2007 to January in Chinese PLA General Hospital were enrolled. The clinical manifestations, laboratory examinations, imaging and pathological data of the 509 patients were retrospectively analyzed.There were totally 406 male patients and 103 female patients. Among all 509 patients, 436 were diagnosed as ankylosing spondylitis (AS)/ spondyloarthropathy (SpA) , including 385 men. Thirty-six cases were diagnosed as sclerosing osteitis. Ten cases were diagnosed as sacroiliac joint degeneration. Ten cases were diagnosed as pyogenic sacroiliitis or sacroiliac joint tuberculosis. Four cases were diagnosed as diffuse idiopathic bone hypertrophy. Four cases were diagnosed as palmoplantar pustulosis arthritis. Four cases were diagnosed as metabolic bone disease. One case was diagnosed as sacroiliac joint gout. Four cases were diagnosed as neoplastic disease. HLA-B27 positive rate was 86.9% in AS/SpA. Erythrocyte sedimentation rate and C-reactive protein were increased mildly-to-moderately in AS/SpA patients. Erythrocyte sedimentation rate and C-reactive protein increased obviously in sacroiliac joint infection and tumor diseases. Imaging characteristics were sacroiliac joint bone destruction. Magnetic resonance imaging showed sacroiliac joint bone marrow edema, but range was not beyond anatomical structure in AS/SpA.Based on disease distribution of sacroiliitis, AS/SpA is predominant while non-ankylosing spondylitis is not uncommon. Differential diagnoses of sacroiliitis should be considered to avoid malpractice, especially in patients with negative HLA-B27.
2013[List of diagnostic tests and procedures in leg ulcer].Acta Med CroaticaMany factors contribute to the pathogenesis of leg ulcer. Most patients have venous leg ulcer due to chronic venous insufficiency. Less often, patients have arterial leg ulcer resulting from peripheral arterial occlusive disease, the most common cause of which is arteriosclerosis. Leg ulcer may be of a mixed arteriovenous origin. In diabetic patients, distal symmetric neuropathy and peripheral vascular disease are probably the most important etiologic factors in the development of diabetic leg ulcer. Other causes of chronic leg ulcers are hematologic diseases, autoimmune diseases, genetic defects, infectious diseases, primary skin diseases, cutaneous malignant diseases, use of some medications and therapeutic procedures, and numerous exogenous factors. Diagnosis of leg ulcer is based on medical history, inspection, palpation of skin temperature, palpation of arteries, fascia holes, presence and degree of edema, firm painful cords, and functional testing to assess peripheral occlusive arterial disease or identify superficial and deep venous reflux of the legs. Knowledge of differential diagnosis is essential for ensuring treatment success in patients with leg ulcer. There are many possible etiologic factors of leg ulcers and sometimes, clinical findings are similar. Additional testing should be performed, e.g., serologic testing such as blood count, C-reactive protein, HBA1c, erythrocyte sedimentation rate, differential blood count, total proteins, electrolytes, coagulation parameters, circulating immune complex, cryoglobulins, homocysteins, AT, PAI-1, APC resistance, proteins C and S, paraproteins, ANA, ENA, ANCA, dsDNA, antiphospholipid antibodies, urea, creatinine, blood lipids, vitamins and trace elements. Also, biopsy of the lesion for histopathology, direct immunofluorescence, bacteriology and mycology should be included. Other tests are Raynaud (cold stimulation) test and pathergy test. Device-based diagnostic testing should be performed for future clarification. Ankle brachial pressure index, color duplex sonography, plethysmography, MSCT and MR angiography, digital subtraction angiography, phlebography, angiography, x-ray, and capillaroscopy in lupus erythematosus are indicated. Except for bacteriologic analyses of wound biopsies, there is no test to provide specific information on the wound condition.
Serum C-reactive protein as a diagnostic biomarker in dogs with bacterial respiratory diseases.J Vet Intern MedC-reactive protein (CRP) is a major acute-phase protein in dogs. Serum concentrations are low in healthy animals, but increase rapidly after inflammatory stimuli.The aim of the study was to investigate CRP concentrations in various respiratory diseases of dogs and to determine if CRP can be used as a biomarker in the diagnosis of bacterial respiratory diseases.A total of 106 privately owned dogs with respiratory diseases (17 with bacterial tracheobronchitis [BTB], 20 with chronic bronchitis [CB], 20 with eosinophilic bronchopneumopathy [EBP], 12 with canine idiopathic pulmonary fibrosis [CIPF], 15 with cardiogenic pulmonary edema [CPE], and 22 with bacterial pneumonia [BP]) and 72 healthy controls.The study was conducted as a prospective cross-sectional observational study. CRP was measured in serum samples. Diagnosis was confirmed by clinical and laboratory findings, diagnostic imaging, and selected diagnostic methods such as cytological and microbiological analysis of respiratory samples, echocardiography, and histopathology.Dogs with BP had significantly higher CRP concentrations (median, 121 mg/L; interquartile range, 68-178 mg/L) than dogs with BTB (23, 15-38, P = .0003), CB (13, 8-14, P < .0001), EBP (5, 5-15, P < .0001), CIPF (17, 10-20, P < .0001), or CPE (19, 13-32, P < .0001) and healthy controls (14, 8-20, P < .0001). Dogs with BTB had significantly higher CRP concentrations than dogs with CB (P = .001) or EBP (P < .0001) and healthy controls (P = .029).These results indicate that CRP has potential for use as an additional biomarker, especially in the diagnostics of BP.
The assessment of treatment efficacy in age related macular degeneration by evaluating the oxidative stress markers and OCT measurements.Rev Med Chir Soc Med Nat IasiAge related macular degeneration (AMD) is the most frequent cause of blindness in the elderly.To establish the role of oxidative stress in retinal structural lesions in AMD and to monitor the evolution of oxidative stress markers and OCT measurements before and after treatment.This is a case-control study that included 19 patients diagnosed with AMD and 40 matched healthy controls. According to the AREDS classification, patients were divided into mild, moderate and severe AMD and received treatment with antioxidants, neurotrophic drugs, intravitreal corticosteroids and/or anti-VEGF. We followed the patients by assessment of visual acuity, optical coherence tomography (OCT) and oxidative stress markers, such as superoxide-dismutase (SOD), thiobarbituric acid reactive substances (TBARS), and C-reactive protein (CRP) from blood samples before and after treatment.The OCT showed that the macular edema in patients with severe disease was significantly reduced after treatment, while the cases with normal retinal thickness increased significantly (p = 0.005). Comparing the mean values of SOD, TBARS and CRP in the two groups, we found that they were significantly higher in the study group compared to controls (p < 0.01), being higher in patients with severe disease. These values decreased post treatment, but they were still higher than in controls.The present research supports the role of oxidative stress and inflammation in AMD and highlights the role of therapy directed against these risk factors. By monitoring the oxidative stress markers in the evolution of the disease, we showed that high values persist after treatment, thus supporting the idea that treatment should be followed for a long time.
Atypical sino-orbital inflammatory myofibroblastic tumor with bone and cerebral invasion extending to the orbit.Eur J OphthalmolTo report the case of an atypical sino-orbital inflammatory myofibroblastic tumor.Case report.A 71-year-old man presented slowly progressive painless diplopia followed by unilateral proptosis of the left eye with slight edema of the upper eyelid. Visual acuity was 0.4 with a relative afferent pupillary defect (RAPD). Abduction and depression of the left eye were limited. Imaging showed a left sino-orbital tumor with mass effect on the medial rectus muscle resulting in proptosis. The lesion showed intracranial extension through the superior orbital fissure with bone erosion and sclerotic bone reaction. Endoscopic ethmoidal, maxillary, and orbital biopsies revealed an inflammatory myofibroblastic tumor. Full blood count showed an eosinophilia while antineutrophil cytoplasmic antibodies and C-reactive protein were negative. To date, 7 cases of orbital myofibroblastic tumor have been described, though none of the prior studies have described bone invasion.This erosive sino-orbital inflammatory myofibroblastic tumor is a novel finding mimicking a malignant tumor.
2013Treatment for cutaneous arteritis patients with mononeuritis multiplex and elevated C-reactive protein.J DermatolCutaneous arteritis (cutaneous polyarteritis nodosa, CA) is a necrotizing vasculitis of arteries within the skin. CA is a new classification under single-organ vasculitis, as adopted by the 2012 Chapel Hill consensus conference (CHCC 2012). Some patients originally diagnosed as having CA could develop additional disease manifestations that warrant reclassifying as systemic polyarteritis nodosa (PAN) according to the CHCC 2012. We retrospectively investigated 101 patients with CA seen at our department between 2003 and 2012. There was a significantly higher frequency of inflammatory plaques and leg edema in CA patients with elevated C-reactive protein (CRP) compared to CA patients with normal CRP. Similarly, there were significant differences in the incidence of arthralgia and mononeuritis multiplex between the two patient groups. We found significantly positive correlations between CRP and creatinine titers in serum in all 101 CA patients. Prednisolone was administrated in a significantly greater percentage of patients with elevated CRP compared to patients with normal CRP. Repeated i.v. cyclophosphamide pulse therapy (IV-CY) with prednisolone therapy at an early stage resulted in complete resolution without adverse effects or severe complications. We regard inflammatory plaques and leg edema with elevated serum CRP as an indication of a more severe condition, and treated them effectively with prednisolone. Assuming mononeuritis multiplex and/or arthritis exist with elevated CRP, we propose that earlier treatment by IV-CY with prednisolone should be indicated for CA patients who demonstrate these more severe manifestations to prevent progression to PAN.
2013[What is ascertained in the therapy of axial spondyloarthritis?].Internist (Berl)The new term axial spondyloarthritis (axSpA) includes classic ankylosing spondylitis and non-radiographic (nr-) axSpA. The definition was introduced in 2009 as part of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA, where-apart from chronic back pain starting before the age of 45 years and the presence of HLA-B27-magnetic resonance imaging demonstrated bone marrow edema of the sacroiliac joints (osteomyelitis) or structural changes on x-rays may play an important role. These criteria can also be used for diagnosis. A major advantage of the new criteria is the identification of patients in early disease stages. In addition to physical therapy, drug treatment with steroidal anti-inflammatory agents (NSAIDs), corticosteroid injections, and biologics [blocker of tumor necrosis factor (TNF)] have all been shown to be effective, while conventional disease modifying drugs (DMARDs) such as sulfasalazine and methotrexate seem to work mainly for peripheral arthritis but not for enthesitis. Biologics are indicated when NSAIDs in optimal dosage have failed. Both these drugs have the potential to improve pain, stiffness, and function but they may also have an influence on new bone formation (syndesmophytes). NSAIDs need to be given continuously and biologics for longer periods of time. Patients with elevated C-reactive protein levels benefit most when treated consequently.
[Accidental intoxication with methotrexate--a case report].Arch Med Sadowej KryminolThe report presents a case of a 49-year-old man, who was accidentally intoxicated with methotrexate. The man was admitted to a nephrology ward because of generalized erythema involving the entire body, skin pruritus, face edema, fever and difficulty with breathing. On the day of admission, additional studies demonstrated a moderate degree of anemia, considerable leucopenia, thrombocytopenia and an increased level of C-reactive protein. In the course of hospitalization, doctors suspected the condition of the patient to be possibly caused by generalized infection, toxic lesion of the bone marrow or hematological bone marrow disease. Finally it was established that the cause of the patient's disease was his erroneous taking of a total of 35 mg of methotrexate (5 mg per day for seven days). Despite intensive treatment, the patient died seven days after admission. Autopsy confirmed that the man died from acute circulatory and respiratory insufficiency caused by intoxication with methotrexate.
2013Certolizumab pegol in axial spondyloarthritis.Expert Rev Clin ImmunolThe axial spondyloarthritis (SpA) classification criteria cover both patients with ankylosing spondylitis and non-radiographic axial SpA. After failure of NSAIDs TNF-α-inhibitors (TNF-blockers) can be given to patients with active axial SpA. Until recently, the TNF-blockers infliximab, adalimumab, etanercept and golimumab are labeled for the treatment of active ankylosing spondylitis while for active nr-axSpA only adalimumab has been approved in Europe. The TNF-blocker certolizumab pegol has recently been evaluated in the RAPID-axSpA trial which is the first placebo-controlled randomized-controlled trial in the entire group of axial SpA. An elevated C-reactive protein and/ or evidence of bone marrow edema on MRI of the sacroiliac joints were required for inclusion in RAPID-axSpA, and patients could have been preexposed to TNF-blockers. The interesting data of this important trial in the context of the emerging therapeutic field of non-radiographic axial SpA therapy is discussed in this review.
2013Leg lymphedema caused by iliopectineal bursitis associated with destruction of a rheumatoid hip joint: A case report.Exp Ther MedThe present study describes a case of leg lymphedema due to iliopectineal bursitis associated with rheumatoid arthritis (RA), which was satisfactorily controlled by surgery and combination therapy with methotrexate (MTX) and tacrolimus. A 68-year-old male, who had a six-year history of RA, developed an iliopectineal bursa associated with destruction of the hip joint. The mass gradually increased in size, and there was swelling in his right lower extremity. The patient was subsequently hospitalized with increasing right hip pain and leg edema. A colorless transparent lymph fluid leaked from his leg, and leg lymphedema was thus diagnosed. The patient also had a 20-year history of myelodysplastic syndrome. Therefore, the extensive or total resection of the bursa was considered to be too invasive, so a partial bursal excision was performed via an anterior approach. Following the partial bursal excision, total hip arthroplasty (THA) was performed using the Hardinge approach. The leg lymphedema disappeared following the surgery, and the iliopectineal bursa was no longer enlarged. MTX and tacrolimus were postoperatively administered to strictly control the RA. The RA was subsequently well controlled, without any increases in the levels of inflammatory markers, such as C-reactive protein and matrix metalloproteinase-3. This case demonstrated that iliopectineal bursitis was resolved following THA, without complete excision of the intrapelvic bursa, and that strict RA control led to a good clinical course without recurrent inflammation of the bursa. Similar procedures may be beneficial in other patients contraindicated for resection of the entire bursa.
2013Elevation of carbohydrate antigen 125 in chronic heart failure may be caused by mechanical extension of mesothelial cells from serous cavity effusion.Clin BiochemThe practical application of elevated carbohydrate antigen 125 (CA125) to predict clinical outcome in chronic heart failure (CHF) is under debate. The mechanism for this CA125 elevation remains unknown. We hypothesize that mechanical stress on mesothelial cells initiates CA125 synthesis.A total of 191 patients suffering from edema and/or dyspnea were enrolled. 109 patients were diagnosed as CHF, and 82 patients without CHF were assigned as control group. Echocardiography, CA125, N-terminal pro-brain natriuretic peptide (NT-proBNP), and other biochemical parameters were measured. All enrolled patients underwent heart function classification.Patients with serous cavity effusion (SCE) demonstrated higher serum CA125 than patients without SCE (82.91 (61.90-103.92) vs. 44.98 (29.66-60.30) U/mL, P<0.001). In the absence of SCE, CA125 levels in CHF patients were slightly higher than non-CHF patients (52.37 (34.85-69.90) vs. 35.15 (23.81-46.49) U/mL, P=0.017). Additionally, compared with non-CHF patients, CHF patients had higher levels of high-sensitivity C-reactive protein (hsCRP) and lower superoxide dismutase (SOD). In all enrolled patients, CA125 levels were negatively correlated with SOD concentrations (r=-0.567, P<0.001), and positively correlated with hsCRP levels (r=0.608, P<0.001). Receiver operating characteristic curve analysis showed that CA125 was better in predicting SCE than NT-proBNP, while NT-proBNP was more suitable for predicting CHF than CA125. The in vitro study demonstrated that MUC16, the CA125 coding gene, was up-regulated by mechanical stretch on human mesothelial cell line (MeT-5A).CA125 elevation in CHF was associated with SCE. Mechanical extension of mesothelial cells from SCE plays an important role in CA125 increase.
2013Diagnosis of early sacroiliitis in seronegative spondyloarthropathies by DWI and correlation of clinical and laboratory findings with ADC values.Eur J RadiolSacroiliitis is one of the diagnostic criteria of seronegative SpA. The purpose of our study is to show the signal characteristics of the sacral and iliac surfaces by DWI which may contribute in early diagnosis of sacroiliitis and investigate the correlation between ADC values and clinical and laboratory parameters.62 patients with inflammatory low back pain, with a history or suspect of seronegative SpA are enrolled into the study. 40 age and sex-matched subjects without SpA constituted the control group. After obtaining routine T1 and T2 weighted sequences, echo planar imaging at b values of 0, 400 and 800 was performed. ADC values on both surfaces of the both sacroiliac joints were measured in all subjects. The CRP and sedimentation results and the presence of arthritis and enthesitis were also correlated with the ADC values.ADC values on both surfaces of the both sacroiliac joints were found 0.23 × 10(-3)mm(2)/sn in the control group. In the patient group, mean ADC value of 0.48 × 10(-3)mm(2)/sn was obtained (p<0.001), which was statistically significant, compatible with the increased diffusion due to medullary edema in early sacroiliitis. There was a slight correlation between CRP and ADC values; presumed to be showing the relation between the activity of the disease and the active inflammation on DWI. There was no correlation between arthritis and enthesitis and the ADC values (p>0.001).DWI, by measuring ADC values, adds significant information in the early diagnosis of sacroiliitis and may help to evaluate the efficiency of the treatment.
2013Peroxisome proliferator-activated receptor γ agonist effect on rheumatoid arthritis: a randomized controlled trial.Arthritis Res TherRheumatoid arthritis (RA), a chronic inflammatory disease, is associated with insulin resistance. Experimental evidence indicates that the relationship between insulin resistance and inflammation is bidirectional: Inflammation promotes insulin resistance, and insulin resistance promotes inflammation. Therefore, we examined the hypothesis that pioglitazone, a thiazolidinedione peroxisome proliferator-activated receptor γ agonist, would decrease inflammation and disease activity and improve insulin resistance in patients with RA.In a single-center, randomized, double-blind, placebo-controlled crossover study patients with RA (N = 34) receiving stable therapy were randomized to also receive either pioglitazone 45 mg daily (n = 17) or matching placebo (n = 17) for eight weeks. This was followed by a four-week washout period and alternative treatment for eight weeks. Outcomes included change in Disease Activity Score in 28 joints (DAS28) score, individual components of the DAS28 score and homeostatic model assessment for insulin resistance (HOMA). Intention-to-treat analysis and linear mixed-effects models were used.Patients had a mean (± SD) age of 51 (± 14.2) years, 82.4% were female and baseline DAS28 high-sensitivity C-reactive protein (DAS28-CRP) was 4.58 (± 1.1) units. Addition of pioglitazone was associated with a 9.3% reduction (95% confidence interval (CI) = 0.17% to 17.6%) in DAS28-CRP (P = 0.046), but no significant change in DAS28 erythrocyte sedimentation rate (DAS28-ESR) (P = 0.92). There was a 10.7 mm (95% CI = 0.4 to 20.9 mm) improvement in patient-reported global health (P = 0.042), a 48.6% decrease (95% CI = 27.6% to 63.5%) in CRP (P < 0.001) and a 26.4% decrease (95% CI = 3.7% to 43.8%) in insulin resistance as measured by HOMA (P = 0.025), but no significant reduction in swollen or tender joint count or in ESR (all P > 0.05). Lower-extremity edema was more common during pioglitazone treatment (16%) than placebo (0%).Addition of pioglitazone to RA therapy improves insulin resistance and modestly reduces RA disease activity measured by DAS28-CRP and two of its components, including patient-reported global health and CRP, but not DAS28-ESR or ESR.NCT00763139.
2014Mesenchymal stromal cells versus betamethasone can dampen disease activity in the collagen arthritis mouse model.Clin Exp MedThe objective of this study was to compare between the effects of mesenchymal stem cell (MSC) and betamethasone in the treatment of rheumatoid arthritis. Sixty male albino mice were divided equally into 2 models. They are MSC model, group 1: saline control group, group 2: collagen-induced arthritis (CIA), group 3: induced arthritis mice that received intravenous injection of MSCs. Betamethasone model, group 1: phosphate buffer saline, group 2: CIA, group 3: induced arthritis mice that received intraperitoneal injection of betamethasone. Mice arthritis models were assessed by clinical paw edema and X-rays, at the proper time of sacrefaction, tissues were collected and examined using real-time PCR, and synovial tissue was examined for interleukin-10, tumor necrosis factor α, cartilage oligomeric matrix protein and matrix metalloproteinase 3. While serum levels of rheumatoid factor and C-reactive protein were detected by enzyme-linked immunosorbent assay kits. Also blood erythrocyte sedimentation rate was detected. Histopathological, paw edema and PCR results showed improvement in the groups that received MSC compared with the diseased group and the groups which received betamethasone. MSC significantly enhanced the effect of collagen-induced arthritis treatment, which is superior to betamethasone treatment, likely through the modulation of the expression of various cytokines.
2013MEFV gene mutations in Henoch-Schönlein purpura.Int J Rheum DisCoexistence of familial Mediterranean fever (FMF) with various systemic vasculitides, including Henoch-Schönlein purpura (HSP) and other inflammatory disorders has been reported and the MEFV gene has been suggested to play an important role in the pathogenesis of this association. In the present study, the mutation rate of the MEFV gene in HSP and its association with the clinical course of the disease were evaluated.The study group comprised 68 children (36 boys and 32 girls) diagnosed as having HSP. The spectrum and degree of organ involvement and the levels of serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were documented for each patient. Allele-specific PCR using oligonucleotide probes which include 12 MEFV mutations (E148Q, P369S, F479L, M680I [G/C], M680I [G/A], I692del, M694V, M694I, K695R, V726A, A744S, R761H) were used for mutation analysis.Of the 68 patients studied, 50 (74%) showed no mutation, while 18 (26%) had MEFV mutation. Mutation analysis of the whole group revealed that 15 (22%) patients were heterozygous for one of the screened MEFV mutations, while three (4.5%) patients were compound heterozygous for two of the studied mutations, and one (1.5%) patient was homozygous for E148Q/E148Q mutations. Gastrointestinal and joint involvement, and edema were more frequently observed in patients with MEFV mutations, while ESR and CRP levels were significantly higher (P < 0.05) in patients with MEFV mutations.MEFV mutations, especially, E148Q and M694V, mutations might be associated with HSP and may affect clinical presentation and laboratory findings in HSP patients.
2013Two rare cases of adult-onset phalangeal microgeodic syndrome with magnetic resonance imaging-proven bone edema transiently occurring in winter.Joint Bone SpineWe report two rare cases of adult-onset phalangeal microgeodic syndrome (PMS), which commonly develops in children. Both cases were Japanese women, with case 1: 60 years old and case 2: 58 years old. They developed swelling and stiffness in their fingers in winter, and their symptoms disappeared without any treatment in summer. Magnetic resonance imaging (MRI) of bilateral hands showed diffuse bone edema of the middle and proximal phalanges in winter, but the abnormal findings also disappeared in summer. The specific abnormalities observed on MRI were very useful for the diagnosis of PMS. Interestingly, they appeared in winter and disappeared in summer in parallel with the symptoms.
Vesiculobullous dermatomyositis with sensory motor neuropathy.SkinmedA 74-year-old man presented with muscle weakness in both legs for a duration of 2 months. Physical examination revealed periorbital edema and erythema, erythema on the neck and chest, erythematous papules on the proximal-distal interphalangeal and metocarpophalangeal joints, crusted plaque lesions on the thighs and around the knees, and bullous and ulcerated lesions in the antecubital and popliteal fossae (Figure 1A and 1B). Some bullous lesions were intact and some were ulcerated. There was severe edema especially in the upper extremities. He had a history of 15-kg weight loss for 4 months. Laboratory findings were remarkable for a white blood cell count of 16.0 K/UL (4.60-10.20 K/UL), a C-reactive protein of 6.93 mg/dL (0-0.5 mg/dL), an erythrocyte sedimentation rate of 50 mm/h (8-15 mm/h), an aspartate aminotransferase level of 213 U/L (10-40 U/L), a lactate dehydrogenase of 447 U/L (< 225 U/L), and a creatine kinase level of 1733 U/L (29-200 U/L). Results from antinuclear antibody at 1:320 titers and anti-smooth muscle antibody were positive. Results from anti-SS A/SS B antibodies, anti Jo-1 antibody, U1-snRNP antibody, and anti-ds DNA antibody tests were negative. A skin biopsy specimen obtained from the right antecubital fossa showed minimal orthokeratosis and subepidermal detachments. There was marked edema in the dermis and lymphocyte infiltration around the skin appendages (Figure 2). Direct immunofluorescence studies demonstrated scattered staining for C3 and IgM at the basal membrane zone. Results for IgG, IgA, and fibrin staining were negative. Muscle biopsy from left deltoid muscle was performed and some muscle fibers were demonstrated to be atrophied. There was remarkable difference between muscle fiber diameters. With Masson staining, there was increased connective tissue and no inflammation. Electromyography (EMG) showed a myogenic pattern. Nerve conduction studies showed tibial, median, ulnar, peroneal motor neuropathy, and median, ulnar, and sural sensory neuropathy. Based on these findings, diagnosis of vesiculo-bullous dermatomyositis (DM) was made. Further investigation of esophagogastroduodenoscopy with biopsy revealed ulcerated lesions on antrum and corpus and these were assessed as Helicobacter pylori-negative atrophic chronic gastritis. No pathologic findings were described on chest, abdomen, and pelvic tomography. Levels of tumor markers were within normal ranges. Overall, no sign of malignancy was detected. Methyl prednisolone treatment of 1 mg/kg/d was started; however, new bullous lesions erupted while the original lesions were healing.
2013Evaluation of anti-inflammatory potential of the multidrug herbomineral formulation in male Wistar rats against rheumatoid arthritis.J Ayurveda Integr MedImmunological and inflammatory mechanisms, which may play a role in a number of disorders like rheumatoid arthritis (RA). Ancient ayurvedic physicians had developed certain dietary and therapeutic measures to arrest or prevent these disorders.Rheuma off gold (RG) is a herbomineral formulation recommended by ayurvedic medical practitioners for treatment of RA. This study was carried out to lend scientific evidence to the efficacy claim for RG in the management of RA in folklore medicine.Arthritis was induced by complete Freund's adjuvant. Treatment with formulation 100 mg/kg and dexamethasone 2 mg/kg was given to rats intragastrically once a day from day 1 to day 21 and after which estimation of physical, biochemical, and hematological parameters were carried out.Treatment of formulation to adjuvant induced arthritic animal showed statistically significant (P < 0.05) improvement in physical parameters like arthritic index, paw edema, paw thickness as well as reduction of inflammatory markers like C-reactive protein, serum rheumatoid factor, erythrocyte sedimentation rate. The treatment also produced statistically significant (P < 0.05) increase in hemoglobin percent and improvement in splenomegaly and thymus index. In the histopathological examination, ameliorative effect of formulation was observed in hyperplasia of synovium, pannus formation, and destruction of the joint space.The results obtained in experiments indicated that the formulation significantly inhibited the adjuvant-induced arthritis which was comparable to dexamethasone and had preferable anti-inflammatory effect without significant side effect. Thus, the formulation may be a potential preventive or therapeutic candidate for the treatment of chronic inflammation and arthritis.
2013"Bath salts" induced severe reversible cardiomyopathy.Am J Case RepMale, 27 FINAL DIAGNOSIS: Bath salt induced cardiomyopathy Symptoms: Agitation • fever • pedal edemaIntravenous nor-epinephrine for less than 6 hours Clinical Procedure: - Specialty: Internal medicine • cardiology.Unusual clinical course."Bath salts" is the street name for a group of recently identified and increasingly abused stimulant synthetic cathinones that are associated with multiple systemic effects. We present a case of a patient who developed reversible dilated cardiomyopathy secondary to their use.A 27 year old male with no past medical history was brought to emergency department with agitation. He had been inhaling and intravenously injecting "bath salts", containing a mephedrone/Methylenedioxypyrovalerone (MDPV) combination. On presentation, he was tachycardic, hypotensive and febrile. His initial labs showed an elevated white count, creatinine and creatinine phosphokinase levels. His erythrocyte sedimentation rate; C-reactive protein; urinalysis; urine drug screen; Human Immunodeficiency Virus, hepatitis, coxsackie, and influenza serology were normal. EKG showed sinus tachycardia. An echocardiogram was done which showed dilated cardiomyopathy with an ejection fraction (EF) of 15-20% and global hypokinesia. A left heart catheterization was done and was negative for coronary artery disease. At a 20 week follow up, he had stopped abusing bath salts and was asymptomatic. A repeat echocardiogram showed an EF of 52%.Bath salts (MDPV, mephedrone) are synthetic cathinones with amphetamine/cocaine like properties with potential cardiotoxic effects. Cardiovascular manifestations reported include tachycardia, hypertension, myocardial infarction, arrhythmias and cardiac arrest. "Bath salts" can also cause severe reversible dilated cardiomyopathy. Prior to diagnosis, other causes of cardiomyopathy including ischemic, infectious, familial, immunological, metabolic and cytotoxic may need to be ruled out; as was done in our patient.
2013[Hemophagocytic syndrome after kidney transplant in a patient with hereditary nephritis. Report of one case].Rev Med ChilWe report a 28-year-old mole with a hereditary nephritis (Alport Syndrome) on hemodialysis for 5 years, who received a kidney graft from a deceased donor. Cyclosporine (CsA), mycophenolate mofetil (MMF) and steroids were prescribed. In the postoperative period the patient had thrombophlebitis and diarrhea. A CT sean showed splenomegaly, ascites, bilateral pleural effusion and bowel edema. Laboratory showed hypoalbuminemia, increased C reactive protein (CRP) and panhypogammaglobulinemia. At day 32 after transplantation, an acute rejection (Banff II b) was diagnosed and treated with methylprednisolone, replacing CsA by tacrolimus. The acute rejection was controlled but six days later, high fever, pancytopenia and hyperferritinemia appeared. A bone marrow smear showed numerous histiocytes and hemophagocytosis. Hemophagocytic syndrome was diagnosed. MMF and tacrolimus were withdrawn and CsA was reinstituted. Fever fell quickly, CPR normalized at 24 hours and white blood cell count at 72 hours. Days later, the concentrations of albumin, immunoglobulins and hematological parameters normalized. The patient was discharged on day 57 after admission in good condition.
2013Human CRP defends against the toxicity of circulating histones.J ImmunolC-reactive protein (CRP) is an acute-phase protein that plays an important defensive role in innate immunity against bacterial infection, but it is also upregulated in many noninfectious diseases. The generic function of this highly conserved molecule in diseases that range from infection, inflammation, trauma, and malignancy is not well understood. In this article, we demonstrate that CRP defends the human body against the toxicity of histones released into the circulation after extensive cell death. In vitro, CRP significantly alleviates histone-induced endothelial cell damage, permeability increase, and platelet aggregation. In vivo, CRP rescues mice challenged with lethal doses of histones by inhibiting endothelial damage, vascular permeability, and coagulation activation, as reflected by significant reductions in lung edema, hemorrhage, and thrombosis. In patients, elevation of CRP significantly increases the capacity to neutralize extracellular histones in the circulation. We have also confirmed that CRP interacts with individual histones in vitro and forms CRP-histone complexes in serum from patients with both elevated CRP and histones. CRP is able to compete with phospholipid-containing liposomes for the binding to histones. This explains how CRP prevents histones from integrating into cell membranes, which would otherwise induce calcium influx as the major mechanism of cytotoxicity caused by extracellular histones. Because histone elevation occurs in the acute phase of numerous critical illnesses associated with extensive cell death, CRP detoxification of circulating histones would be a generic host defense mechanism in humans.
2013[Proptosis and ophthalmoplegia after cataract surgery].HarefuahWe report a case of a 57 years old female presenting with proptosis, periorbital swelling and ophthalmoplegia, 4 days after an uneventful phacoemucification surgery. Visual acuity was 20/200, biomicroscopy showed mild corneal edema and anterior chamber cells with normal posterior segment. The patient was febrile with leukocytosis and elevated Levels of C-reactive protein. A head computed tomography venography scan showed left eye proptosis, bilateral paranasal sinus hyper-density with massive sinus vein thrombosis extending from the left ophthalmic vein to the left cavernous, transversal and sigmoidal sinuses, the right cavernous and sigmoidal sinuses and internal jugular veins bilaterally. Very mild infiltration was seen around the Left ophthalmic vein, with no other signs of orbital inflammation. Emergency endoscopic sinus surgery was performed followed by anticoagulation and antibiotic treatment, blood and sinus culture later grew streptococci. The therapeutic measures resulted in complete resolution of the ocular and systemic findings.
Efficacy and safety of adding pioglitazone or sitagliptin to patients with type 2 diabetes insufficiently controlled with metformin and a sulfonylurea.Endocr PractTo evaluate the efficacy and safety of add-on pioglitazone versus sitagliptin in patients with type 2 diabetes inadequately controlled on metformin and a sulfonylurea (SU).This 24-week, randomized, open-label study compared pioglitazone (30 mg daily, n = 59) and sitagliptin (100 mg daily, n = 60) in patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] ≥7.0% to <11.0%) while receiving a stable dose of metformin (≥1,500 mg daily) and an SU (≥half-maximal dose).The mean changes in HbA1c from baseline was -0.94 ± 0.12% with pioglitazone and -0.71 ± 0.12% with sitagliptin, for a between-groups difference of -0.23 ± 0.16% (P = .16). The mean change in fasting plasma glucose (FPG) were -35.7 ± 4.0 mg/dL with pioglitazone and -22.8 ± 4.0 mg/dL with sitagliptin, for a between-groups difference of -12.9 ± 5.7 mg/dL (P = .02). Pioglitazone was associated with a significant decrease in high-sensitive C-reactive protein (hs-CRP), but sitagliptin did not. The mean weight gain was higher in the pioglitazone group, with a between-group difference of 1.6 kg (P<.01). Overall adverse events (AEs) were similar in both groups. However, the incidence of edema was higher with pioglitazone, and the incidence of gastrointestinal AEs was higher with sitagliptin.Pioglitazone and sitagliptin achieved similar improvements in overall glycemic control in patients with type 2 diabetes inadequately controlled with metformin and an SU. However there were some differences in terms of FPG, hs-CRP, lipids, body-weight change, and AEs.
2014LED therapy or cryotherapy between exercise intervals in Wistar rats: anti-inflammatory and ergogenic effects.Lasers Med SciThe aim of this study was to test, between two bouts of exercise, the effects of light-emitting diode (LED) therapy and cryotherapy regarding muscle damage, inflammation, and performance. Male Wistar rats were allocated in four groups: control, passive recovery (PR), cryotherapy (Cryo), and LED therapy. The animals were submitted to 45 min of swimming exercise followed by 25 min of recovery and then a second bout of either 45 min of exercise (muscle damage analysis) or time to exhaustion (performance). During the rest intervals, the rats were kept in passive rest (PR), submitted to cold water immersion (10 min, 10 °C) or LED therapy (940 nm, 4 J/cm(2)) of the gastrocnemius muscle. Blood samples were collected to analyze creatine kinase activity (CK), C-reactive protein (CRP), and leukocyte counts. The soleus muscles were evaluated histologically. Time to exhaustion was recorded during the second bout of exercise. After a second bout of 45 min, the results demonstrated leukocytosis in the PR and Cryo groups. Neutrophil counts were increased in all test groups. CK levels were increased in the Cryo group. CRP was increased in PR animals. The PR group presented a high frequency of necrosis, but the LED group had fewer necrotic areas. Edema formation was prevented, and fewer areas of inflammatory cells were observed in the LED group. The time to exhaustion was greater in both the LED and Cryo groups, without differences in CK levels. CRP was decreased in LED animals. We conclude that LED therapy and cryotherapy can improve performance, although LED therapy is more efficient in preventing muscle damage and local and systemic inflammation.
2013Septic liver: clinical relevance of early inhomogeneous enhancement of the liver in patients with acute pyelonephritis.Acta RadiolCT scans of patients with febrile illness occasionally show hepatobiliary changes, although infection does not originate in the hepatobiliary system. These findings may cause radiologists and clinicians to misrecognize hepatobiliary diseases and initiate an inappropriate treatment. Thus, it is important to recognize hepatobiliary CT findings in cases of extrahepatobiliary infectious disease.To evaluate extrarenal CT manifestations in patients with acute pyelonephritis and to determine the correlation between these extrarenal CT findings and septic liver based on laboratory parameters of sepsis.This study included 157 retrospectively identified patients with confirmed acute pyelonephritis based on CT imaging and urine test, and who had also undergone multi-phase dynamic contrast-enhanced CT scan. Two radiologists reviewed CT findings including early inhomogeneous enhancement of the liver, periportal low density and gallbladder edema, which were correlated with laboratory data including liver function enzymes, albumin, C-reactive protein, white blood cell count, and results of a blood culture by using the Fisher's exact test and Mann-Whitney U test.Forty-six patients (29.3%) showed early inhomogeneous enhancement of the liver, which was associated with increased C-reactive protein (P < 0.001), a positive blood culture (P < 0.005), and decreased albumin level (P < 0.002). The periportal low density and gallbladder wall edema were noted in 15 patients (9.6%) and six patients (3.8%), respectively. These two CT findings were significantly associated with only decreased albumin level (P < 0.001 and P < 0.040).Early inhomogeneous enhancement of the liver in patients with acute pyelonephritis was significantly associated with increased CRP level, a positive blood culture and decreased albumin level, reflecting sepsis and sepsis-associated liver dysfunction, requiring rapid and appropriate intensive treatment.
2013Effects of air-pulsed cryotherapy on neuromuscular recovery subsequent to exercise-induced muscle damage.Am J Sports MedLocalized cooling has been proposed as an effective strategy to limit the deleterious effects of exercise-induced muscle damage on neuromuscular function. However, the literature reports conflicting results.This randomized controlled trial aimed to determine the effects of a new treatment, localized air-pulsed cryotherapy (-30°C), on the recovery time-course of neuromuscular function following a strenuous eccentric exercise.Controlled laboratory study.A total of 24 participants were included in either a control group (CONT) or a cryotherapy group (CRYO). Immediately after 3 sets of 20 maximal isokinetic eccentric contractions of elbow flexors, and then 1, 2, and 3 days after exercise, the CRYO group received a cryotherapy treatment (3 × 4 minutes at -30°C separated by 1 minute). The day before and 1, 2, 3, 7, and 14 days after exercise, several parameters were quantified: maximal isometric torque and its associated maximal electromyographic activity recorded by a 64-channel electrode, delayed-onset muscle soreness (DOMS), biceps brachii transverse relaxation time (T2) measured using magnetic resonance imaging, creatine kinase activity, interleukin-6, and C-reactive protein.Maximal isometric torque decreased similarly for the CONT (-33% ± 4%) and CRYO groups (-31% ± 6%). No intergroup differences were found for DOMS, electromyographic activity, creatine kinase activity, and T2 level averaged across the whole biceps brachii. C-reactive protein significantly increased for CONT (+93% at 72 hours, P < .05) but not for CRYO. Spatial analysis showed that cryotherapy delayed the significant increase of T2 and the decrease of electromyographic activity level for CRYO compared with CONT (between day 1 and day 3) in the medio-distal part of the biceps brachii.Although some indicators of muscle damage after severe eccentric exercise were delayed (ie, local formation of edema and decrease of muscle activity) by repeated air-pulsed cryotherapy, we provide evidence that this cooling procedure failed to improve long-term recovery of muscle performance.Four applications of air-pulsed cryotherapy in the 3 days after a strenuous eccentric exercise are ineffective overall in promoting long-term muscle recovery. Further studies taking into account the amount of exercise-induced muscle damage would allow investigators to make stronger conclusions regarding the inefficiency of this recovery modality.
2014Effects and safety of allogenic mesenchymal stem cell intravenous infusion in active ankylosing spondylitis patients who failed NSAIDs: a 20-week clinical trial.Cell TransplantOur objective was to evaluate the feasibility, safety, and efficacy of intravenous (IV) infusion of allogenic mesenchymal stem cells (MSCs) in ankylosing spondylitis (AS) patients who are refractory to or cannot tolerate the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). AS patients enrolled in this study received four IV infusions of MSCs on days 0, 7, 14, and 21. The percentage of ASAS20 responders (the primary endpoint) at the fourth week and the mean ASAS20 response duration (the secondary endpoint) were used to assess treatment response to MSC infusion and duration of the therapeutic effects. Ankylosing Spondylitis Disease Activity Score Containing C-reactive Protein (ASDAS-CRP) and other preestablished evaluation indices were also adopted to evaluate the clinical effects. Magnetic resonance imaging (MRI) was performed to detect changes of bone marrow edema in the spine. The safety of this treatment was also evaluated. Thirty-one patients were included, and the percentage of ASAS20 responders reached 77.4% at the fourth week, and the mean ASAS20 response duration was 7.1 weeks. The mean ASDAS-CRP score decreased from 3.6 ± 0.6 to 2.4 ± 0.5 at the fourth week and then increased to 3.2 ± 0.8 at the 20th week. The average total inflammation extent (TIE) detected by MRI decreased from 533,482.5 at baseline to 480,692.3 at the fourth week (p > 0.05) and 400,547.2 at the 20th week (p < 0.05). No adverse effects were noted. IV infusion of MSCs is a feasible, safe, and promising treatment for patients with AS.
Use of blood markers in early diagnosis of oxidative stress in age related macular degeneration.Rev Med Chir Soc Med Nat IasiAge related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly population, affecting approximately 30-50 million people around the world.to establish the role of oxidative stress in retinal structural lesions.It is a case-control study that included 19 patients diagnosed with AMD. Depending on the severity of the diagnosis, patients were divided into 3 groups: group 1 - mild AMD, group 2 - moderate, atrophic AMD, group 3 - severe, neovascular AMD. They were followed by assessment of visual acuity, optical coherence tomography (OCT) and oxidative stress markers like superoxide-dismutase (SOD), thiobarbituric acid reactive substances (TBARS) and inflammatory marker - C-reactive protein (CRP).Risk factors involved in patients with AMD are arterial hypertension, smoking, hyperlipidemia and diet poor in antioxidants, as revealed in the questionnaire. Retinal thickness assessed by optical coherence tomography showed that values in patients with severity level 2 is within normal limits, while in patients with severity level 3, these values are significantly increased due to macular edema. The mean values of SOD, TBARS and CRP in the studied group were significantly higher compared to controls, being higher in group severity level 3.This study shows the role of oxidative stress and inflammation in retinal structural lesions in AMD and the importance of blood markers in early detection of oxidative stress and thus of retinal lesions in this disease.
2013Simvastatin attenuates neutrophil recruitment in one-lung ventilation model in rats.Acta Cir BrasTo investigate the anti-inflammatory effects of simvastatin in rats undergoing one-lung ventilation (OLV) followed by lung re-expansion.Male Wistar rats (n=30) were submitted to 1-h OLV followed by 1-h lung re-expansion. Treated group received simvastatin (40 mg/kg for 21 days) previous to OLV protocol. Control group received no treatment or surgical/ventilation interventions. Measurements of pulmonary myeloperoxidase (MPO) activity, pulmonary protein extravasation, and serum levels of cytokines and C-reactive protein (CRP) were performed.OLV significantly increased the MPO activity in the collapsed and continuously ventilated lungs (31% and 52% increase, respectively) compared with control (p<0.05). Treatment with simvastatin significantly reduced the MPO activity in the continuously ventilated lung but had no effect on lung edema after OLV. The serum IL-6 and CRP levels were markedly higher in OLV group, but simvastatin treatment failed to affect the production of these inflammatory markers. Serum levels of IL-1β, TNF-α and IL-10 remained below the detection limit in all groups.In an experimental one-lung ventilation model pre-operative treatment with simvastatin reduces remote neutrophil infiltration in the continuously ventilated lung. Our findings suggest that simvastatin may be of therapeutic value in OLV-induced pulmonary inflammation deserving clinical investigations.
2013Incomplete Kawasaki disease.Am J Emerg MedThis is a report of a 4-year-old Hispanic boy who presented with skin changes to the lips and oral cavity, a generalized rash, edema of hands and feet, and peeling of the periungual areas of the fingers as well as to the groin and perianal areas. Fourteen days earlier, his 19-month-old brother was diagnosed and treated for Kawasaki disease. Upon laboratory investigation, our patient was found to have an elevated sedimentation rate, C-reactive protein, and serum γ-glutamyl transferase. Infectious disease and cardiology consultations subsequently diagnosed and treated our patient for incomplete Kawasaki disease.
2013Natriuretic peptide type B in burn intensive care.J Trauma Acute Care SurgThe plasma concentration of natriuretic peptide type B (BNP) or NT-proBNP (P-BNP or P-NT-proBNP) reflects cardiac load. In intensive care unit settings and in chronic inflammation, it is also affected by non-heart-related mechanisms. It has been suggested to be a marker of hydration after severe burns and to predict outcome in critically ill patients, but results are contradictory. We therefore measured P-NT-proBNP after severe burns and related it to injury related variables and to organ dysfunction.Fifty consecutive patients with a burn size greater than 10% were studied for the first 2 weeks. P-NT-proBNP changes were analyzed in relation to burn size, age, changes in body weight, C-reactive protein in plasma, and organ function assessed as Sequential Organ Failure Assessment (SOFA) scoresP-NT-proBNP showed large day-to-day and between patient variations. Daily change in body weight correlated with P-NT-proBNP only on Day 2, when maximum mobilization of edema occurred. Thereafter, P-NT-proBNP correlated with C-reactive protein in plasma as well as with SOFA scores. Burn size correlated with maximal weight change, which in turn correlated with both time for and value of maximum P-NT-proBNP. Maximal P-NT-proBNP was related to mortality and correlated better with SOFA score on Day 14 compared with age and burn size. In linear regressions, together with age at injury and total body surface area, P-NT-proBNP assessed on Days 3 to 8 was an independent predictor for every subsequent SOFA score measured one or more days later up to Day 14.P-NT-proBNP exhibited considerable interindividual and day-to-day variations. Values were related to mortality, burn size, water accumulation, posttraumatic response, and organ function. Maximum P-NT-proBNP correlated stronger with length of stay and with organ function on Day 14, compared with age and burn size. High values in Days 3 through 8 were also independent predictors of subsequent organ function up to 2 weeks after injury.Epidemiologic/prognostic study, level III.
2013Prospective study of inflammatory biomarkers and risk of diabetic retinopathy in the diabetes control and complications trial.JAMA OphthalmolThis study demonstrates that increasing quintiles of baseline high-sensitivity C-reactive protein (hsCRP) level may be associated with higher risk of incident clinically significant macular edema, the leading cause of vision loss in working-aged individuals in North America.To determine whether baseline levels of hsCRP and intercellular adhesion molecule 1 (ICAM-1) predict development and progression of diabetic retinopathy (DR), clinically significant macular edema (CSME), retinal hard exudates, and proliferative DR in the Diabetes Control and Complications Trial (DCCT) cohort.The DCCT was a large multicenter randomized controlled clinical trial.Twenty-nine medical centers in the United States and Canada.The DCCT population consisted of 1441 subjects with type 1 diabetes mellitus aged 13 to 39 years at study entry.We measured levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 in stored baseline blood samples.We assessed the association of levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 with incident DR end points ascertained from grading of standardized 7-field stereoscopic retinal color photographs taken at baseline and every 6 months during follow-up.After adjustment for randomized treatment assignment and other factors, we observed a statistically significant association between hsCRP and risk of CSME, with a relative risk (RR) for the top vs bottom quintile of 1.83 (95% CI, 0.94-3.55; P for trend = .01). Similarly, for the development of retinal hard exudates, the RR for the top vs bottom quintile of hsCRP level was 1.78 (95% CI, 0.98-3.25; P for trend = .004), whereas for ICAM-1 level, the RR comparing the top vs bottom quintiles was 1.50 (95% CI, 0.84-2.68; P for trend = .05). There were no statistically significant associations between baseline VCAM-1 or tumor necrosis factor α receptor 1 levels and risk of any of the DR end points.After adjusting for known risk factors, increasing quintiles of baseline hsCRP level may be associated with higher risk of incident CSME and macular hard exudate in the DCCT cohort. Circulating levels of ICAM-1 may also be associated with the development of retinal hard exudates.
2013Predictors of cardiogenic and non-cardiogenic causes in cases with bilateral chest infiltrates.Tuberc Respir Dis (Seoul)Differentiating cardiogenic pulmonary edema from other bilateral lung diseases such as pneumonia is frequently difficult. We conducted a retrospective study to identify predictors for cardiogenic pulmonary edema and non-cardiogenic causes of bilateral lung infiltrates in chest radiographs.The study included patients who had newly developed bilateral lung infiltrates in chest radiographs and patients who underwent echocardiography. Cases were divided into two groups based on the echocardiographic findings: the cardiogenic pulmonary edema group and the non-cardiogenic group. Clinical characteristics and basic laboratory findings were analyzed to identify predictors for differential diagnosis between cardiogenic and non-cardiogenic causes of bilateral chest infiltrates.We analyzed 110 subjects. Predictors of cardiogenic pulmonary edema were higher brain natriuretic peptide (BNP) levels, lower C-reactive protein (CRP) levels on the day of the event (<7 mg/dL), age over 60 years, history of heart disease, and absence of fever and sputum. CRP on the day of the event was an independent factor to differentiate cardiogenic and non-cardiogenic causes of newly developed bilateral chest infiltrates. Also, the validity was comparable to BNP.Clinical symptoms (sputum and fever), medical history (dyslipidemia and heart disease), and laboratory findings (BNP and CRP) could be helpful in the differential diagnosis of patients with acute bilateral lung infiltrates in chest radiographs.
2013Stellate ganglion block as an early intervention in sympathetically maintained headache and orofacial pain caused by temporal arteritis.Pain MedWe report a case of temporal arteritis with a sympathetic component in the orofacial region, which responded to stellate ganglion blocks (SGBs).An 81-year-old woman with limited mouth opening and pain upon chewing was referred to the Orofacial Pain Clinic at Nihon University Dental Hospital. The patient also presented with blurred vision and a burning sensation on the right side of her face. On clinical examination, the temporal artery was tender to palpation, and there was increased sensitivity in the temporal region bilaterally. The patient reported jaw pain and limited mouth opening. Laboratory examination showed elevations in erythrocyte sedimentation rate and C-reactive protein. The burning sensation was due to a sympathetic component, and SGBs substantially reduced both the burning sensation and right temporal pain. Blocking the sympathetic chain on the ipsilateral side also improved jaw movement. The patient was referred to a rheumatologist, after which she was admitted to hospital with a tentative diagnosis of temporal arteritis. Treatment with oral prednisone 30 mg daily was initiated, and the dose was tapered as her symptoms resolved.The reason for the gradual pain relief after SGB is unclear, but we believe it was effective for ischemia in temporal arteritis because it led to dilation of affected arteries or suppression of inflammation/edema of the vascular wall.This case demonstrates that SGB may relieve pain related to temporal arteritis and sympathetically maintained headache and orofacial pain by reducing noxious stimulation peripherally and decreasing central pain transmission centrally.
2013Lymph-node-first presentation of Kawasaki disease compared with bacterial cervical adenitis and typical Kawasaki disease.J PediatrTo identify characteristics differentiating the node-first presentation of Kawasaki disease (NFKD) from bacterial cervical lymphadenitis (BCL) and typical Kawasaki disease (KD).From our prospectively collected database, we compared clinical, laboratory, and imaging characteristics of NFKD and BCL cohorts and performed multivariable logistic regression to identify variables that distinguish NFKD from BCL. We then compared outcomes of patients with NFKD and patients with typical KD treated during the same period.Over 7 years, 57 patients were hospitalized for NFKD, 78 for BCL, and 287 for typical KD. Patients with NFKD were older and had more medical encounters and longer duration of illness before the correct diagnosis was made than did patients with BCL. Of patients with NFKD, 33% had an admission diagnosis of bacterial adenitis or abscess. Compared with patients with BCL, patients with NFKD had lower leukocyte (white blood cell), hemoglobin, and platelet counts and higher absolute band counts (ABCs), C-reactive protein (CRP), alanine transaminase and γ-glutamyl transpeptidase levels, and erythrocyte sedimentation rates. In the multivariable analysis, smaller nodes, lower white blood cell count, and higher ABC and CRP were independently associated with NFKD. Patients with NFKD had multiple enlarged solid nodes and comparable rates of retropharyngeal edema. Compared with patients with typical KD, patients with NFKD were older, had more severe inflammation, and had similar rates of coronary artery abnormalities and resistance to intravenous immune globulin.High ABC and CRP values and multiple enlarged solid nodes in febrile patients with cervical adenopathy should prompt consideration of NFKD to prevent delayed diagnosis of KD. Retropharyngeal edema on radiography should not dissuade from the diagnosis of NFKD.
2013Serum prealbumin: an independent marker of short-term energy intake in the presence of multiple-organ disease involvement.NutritionSerum prealbumin has a prognostic value in several diseases, but its serum levels can be influenced by different factors. However, a multivariable analysis to test the independent effect of each has not yet, to our knowledge, been performed. The aim of this cross-sectional study was to investigate the association between prealbumin and several factors possibly affecting its serum levels to test the potential of using prealbumin as an indicator of nutritional status and short-term energy intake in patients newly diagnosed with immunoglobulin light-chain amyloidosis.Multivariable general linear regression models of non-collinear variables were fitted to assess the association of demographic (sex, age), nutritional (short-term energy intake, unintentional weight loss, body mass index), and clinical (cardiac and liver involvement, kidney function, C-reactive protein) parameters with serum prealbumin levels in 187 patients newly diagnosed with immunoglobulin light-chain amyloidosis.Serum prealbumin levels were associated with C-reactive protein and short-term energy intake (P < 0.001 for both). A significant association was also detected with age (P = 0.023), serum creatinine (P = 0.017), liver involvement (P = 0.002), and peripheral edema (P = 0.032). In a prespecified subgroup analysis (n = 140) in patients with normal C-reactive protein level (<0.5 mg/dL), all other associations were confirmed. A significant relation was also observed with sex (P = 0.022) and body mass index (P = 0.041).Serum prealbumin is associated with short-term energy intake independently of the presence of multiple-organ involvement and inflammation. Its serum levels should be always interpreted in light of its influencing factors, among which inflammation and liver and kidney functions appear predominant.
2013Acute calcific deposition in the lateral collateral ligament of the knee.J Knee SurgWe present a rare case of a patient presenting with acute onset knee pain, which was subsequently diagnosed and treated as acute calcific deposition in the lateral collateral ligament. A 51-year-old gentleman presented to the emergency department with acute onset, excruciating, and left knee pain. There was no preceding history of trauma or systemic upset. Examination revealed exquisite tenderness over the lateral aspect of the knee with leg edema and an associated knee effusion. Blood tests showed a raised C-reactive protein. Plain radiographs of the knee showed a poorly defined calcific deposition with a "cloud-like" configuration. Following exclusion of all more threatening causes of symptoms, the patient was diagnosed with acute calcific tendinitis. The patient's pain was unremitting despite intravenous opiates, and he was taken to the operation theater for exploration and removal of the irritant crystal deposition from the lateral fibular collateral ligament resulting in complete resolution of symptoms. Acute calcific deposition in the lateral collateral ligament is a rare condition. There have been very few reports of this in the literature to date, and no reported cases of surgical excision. Calcific deposition can be treated successfully using conservative measures with symptoms settling after 4 to 6 weeks, however operative excision has been shown to be appropriate in specific cases. Acute calcific deposition should be considered in patients with unexplained acute knee pain and swelling, following the exclusion of other more common conditions. We present the first operatively treated case with accompanying radiology images, intraoperative medical photography, and histological slides.
2013Assessment of the efficacy and tolerability of 2 formulations of atorvastatin in Korean adults with hypercholesterolemia: a multicenter, prospective, open-label, randomized trial.Clin TherA manufacturer of atorvastatin is seeking marketing approval in Korea of a generic product for adult patients with primary hypercholesterolemia.The objective of this study was to compare the efficacy and tolerability of a new generic formulation of atorvastatin (test) with those of an original formulation of atorvastatin (reference) to satisfy regulatory requirements for marketing of the generic product in Korea.Patients enrolled were aged 20 to 79 years with documented primary hypercholesterolemia who did not respond adequately to therapeutic lifestyle changes and with a LDL-C level >100 mg/dL from a high-risk group of coronary artery disease patients. Eligible patients were randomized to receive 1 of the 2 formulations of atorvastatin 20 mg per day for 8 weeks. The primary end point was the percent change in LDL-C level from baseline to week 8. Secondary end points included the percent change in total cholesterol, triglycerides, HDL-C level, apolipoprotein B:apolipoprotein A-I ratio, LDL:HDL ratio, LDL-C particle size, high-sensitivity C-reactive protein from baseline to week 8, and achievement rate of the LDL-C goal.A total of 298 patients (141 men and 157 women; 149 patients in each group; mean [SD] age, 62.4 [9.2] in the test group vs 60.3 [8.9] years in the reference group) were included. LDL-C levels were significantly decreased from baseline to week 8 in both groups, and there was no significant difference in the percent change in LDL-C level between groups (-44.0% [17.2%] in the test group, -45.4% [16.9%] in the reference group; P = 0.49). The between-group differences in the percent changes in total cholesterol and triglyceride levels were not statistically significant. In addition, there was no significant difference between the 2 groups in percent changes in HDL-C, apolipoprotein B:apolipoprotein A-I ratio, LDL-C:HDL-C ratio, LDL-C particle size, high-sensitivity C-reactive protein, and the achievement rate of the LDL-C goal. Two (1.3%) patients in the reference group (N = 150) experienced treatment-related serious adverse events (AEs): toxic hepatitis and aggravation of chest pain. Common AEs were cough (4.1%), myalgia (2.1%), and indigestion (1.4%) in the test formulation group and cough (5.3%), creatine kinase elevation (2.7%), and edema (0.7%) in the reference formulation group; however, the differences in overall prevalence of AEs between the 2 treatment groups was not significant (P = 0.88).There were no significant differences observed in the efficacy and tolerability between the test and reference formulations of atorvastatin in these Korean adult patients with primary hypercholesterolemia.
2014Inflammation and atrial remodeling after a mountain marathon.Scand J Med Sci SportsEndurance athletes have an increased risk of atrial fibrillation. We performed a longitudinal study on elite runners of the 2010 Jungfrau Marathon, a Swiss mountain marathon, to determine acute effects of long-distance running on the atrial myocardium. Ten healthy male athletes were included and examined 9 to 1 week prior to the race, immediately after, and 1, 5, and 8 days after the race. Mean age was 34.9 ± 4.2 years, and maximum oxygen consumption was 66.8 ± 5.8 mL/kg*min. Mean race time was 243.9 ± 17.7 min. Electrocardiographic-determined signal-averaged P-wave duration (SAPWD) increased significantly after the race and returned to baseline levels during follow-up (128.7 ± 10.9 vs. 137.6 ± 9.8 vs. 131.5 ± 8.6 ms; P < 0.001). Left and right atrial volumes showed no significant differences over time, and there were no correlations of atrial volumes and SAPWD. Prolongation of the SAPWD was accompanied by a transient increase in levels of high-sensitivity C-reactive protein, proinflammatory cytokines, total leucocytes, neutrophil granulocytes, pro atrial natriuretic peptide and high-sensitivity troponin. In conclusion, marathon running was associated with a transient conduction delay in the atria, acute inflammation and increased atrial wall tension. This may reflect exercise-induced atrial myocardial edema and may contribute to atrial remodeling over time, generating a substrate for atrial arrhythmias.
2013Anti-inflammatory activity of lycopene isolated from Chlorella marina on type II collagen induced arthritis in Sprague Dawley rats.Immunopharmacol ImmunotoxicolThe role of commercially available lycopene (all-trans) from tomato in controlling arthritis has been reported. Even though many reports are available that the cis form of lycopene is more biologically active, no report seems to be available on lycopene (cis and trans) isolated from an easily available and culturable sources. In the present study, the anti-arthritic effect of lycopene (cis and trans) from the algae Chlorella marina (AL) has been compared with lycopene (all-trans) from tomato (TL) and indomethacin (Indo). Arthritis (CIA) was developed in male Sprague dawley rats by collagen and the following parameters were studied. The activities of inflammatory marker enzymes like cyclooxygenase (COX), lipoxygenase (LOX) and myeloperoxidase (MPO) were found to be decreased on treatment with AL when compared to TL and Indo. Changes in Erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, red blood cells (RBC) count, hemoglobin (Hb), C-reactive protein (CRP), rheumatoid factor (RF), and ceruloplasmin levels observed in the blood of arthritic animals were brought back to normal by AL when compared to TL and Indo. Histopathology of paw and joint tissues showed marked reduction in edema on supplementation of AL. Thus these results indicate the potential beneficiary effect of algal lycopene on collagen induced arthritis in rats when compared to TL and even to the commonly used anti-inflammatory drug indomethacin. Therefore lycopene from C. marina would be recommended as a better natural source with increased activity and without side effects in the treatment of anti-inflammatory diseases.
2013Anti-inflammatory and antioxidant potential of alginic acid isolated from the marine algae, Sargassum wightii on adjuvant-induced arthritic rats.InflammopharmacologyThe present study evaluated the anti-inflammatory and antioxidant potential of alginic acid isolated from brown algae Sargassum wightii in arthritic rats. Arthritis was induced in male Sprague-Dawley rats by intradermal injection of complete Freund's adjuvant into the right hind paw, produce inflammation of the joint tissue. Paw edema volume, enzymes linked to inflammation such as cyclooxygenase, lipoxygenase and myeloperoxidase, and the level of ceruloplasmin, C-reactive protein and rheumatoid factor were evaluated in all the experimental groups. Oxidative stress during inflammation was analyzed by estimating lipid peroxidation and the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and non-enzymatic antioxidant, reduced glutathione. Alginic acid treatment (100 mg/kg) in arthritic rats exhibited reduced paw edema volume along with reduced activities of enzymes such as cyclooxygenase, lipoxygenase and myeloperoxidase. Reduction in the level of C-reactive protein, ceruloplasmin and rheumatoid factor were also observed in arthritic rats treated with alginic acid along with reduced lipid peroxidation and enhanced activities of antioxidant enzymes, which suggest the antioxidant potential of the compound. Histopathological analysis of paw tissue showed that alginic acid treatment reduced paw edema and inflammatory infiltration in arthritic rats. Overall results suggest that alginic acid isolated from Sargassum wightii exhibits potent anti-inflammatory and antioxidant activity, and can develop this marine alga as an alternative source for therapy and can be used as a drug candidate for the development of anti-inflammatory agent.
2012Onodera's prognostic nutritional index as a risk factor for mortality in peritoneal dialysis patients.J Korean Med SciThe aim of this study was to evaluate the clinical relevance and usefulness of the Onodera's prognostic nutritional index (OPNI) as a prognostic and nutritional indicator in peritoneal dialysis (PD) patients. Patients were divided into 3 groups based on the initial OPNI score: group A (n = 186, < 40), group B (n = 150, 40-45), and group C (n = 186, > 45). Group A was associated with a higher grade according to the Davies risk index than the other groups. Serum creatinine and albumin levels, total lymphocyte count, and fat mass increased with an increase in OPNI. According to the edema index, the correlation coefficient for OPNI was -0.284 and for serum albumin was -0.322. Similarly, according to the C-reactive protein (CRP), the correlation coefficient for OPNI was -0.117 and for serum albumin was -0.169. Multivariate analysis adjusted for age, Davies risk index, CRP, and edema index revealed that the hazard ratios for low OPNI, serum albumin, and CRP were 1.672 (P = 0.003), 1.308 (P = 0.130), and 1.349 (P = 0.083), respectively. Our results demonstrate that the OPNI is a simple method that can be used for predicting the nutritional status and clinical outcome in PD patients.
2013DNA vaccine encoding the major virulence factors of Shiga toxin type 2e (Stx2e)-expressing Escherichia coli induces protection in mice.VaccinePiglet edema disease is found worldwide and has historically been treated with antibiotics. However, no commercial vaccines are available for its prevention. In this study, the two major virulence factors of Shiga-toxigenic Escherichia coli (Stx2eB and FedF) were cloned to a pcDNA6.0 plasmid to develop a novel DNA vaccine against piglet edema disease. In animal trial in mouse model, the antibody titer, mortality, serum cytokine levels (interleukin-1 beta, interleukin-6, tumor necrosis factor alpha and C-reactive protein), serum malondialdehyde level and serum total superoxide dismutase activity were measured to validate the effectiveness of the DNA vaccine. The results show that Stx2eB and FedF at least partially protect against edema disease and FedF is more effective than Stx2eB. Co-immunization with both Stx2eB and FedF is most effective for protecting mice from a subsequent challenge with E. coli O139 (which is known to cause edema disease in pigs).
2012True identity of endocapillary proliferation: a case of intravascular large B cell lymphoma diagnosed with immunohistochemical study of kidney biopsy and literature review.CEN Case RepA 78-year-old Japanese female presented with low-grade fever, malaise, and appetite loss lasting for 1 month. Upper and lower gastrointestinal endoscopy and contrast-enhanced whole-body computed tomography (CT) revealed no abnormal findings at a referring hospital. She was referred to our hospital because of bilateral leg edema and 2.5 g/day proteinuria. Serum creatinine was 0.73 mg/dl and the kidneys were not enlarged. Kidney biopsy showed marked endocapillary proliferation with mesangiolysis. Soon after the kidney biopsy, her symptoms improved spontaneously, along with decreases in lactate dehydrogenase (LDH) from 503 to 197 IU/l, C-reactive protein (CRP) from 4.47 to 0.66 mg/dl, and soluble interleukin-2 receptor (sIL-2R) from 1789 to 1001 U/ml. Thus, she was followed carefully as an outpatient. One month later, however, she presented with dysarthria and right-sided hemiparesis, and diffusion-weighted brain magnetic resonance imaging (MRI) showed multiple high-intensity areas. She also had respiratory failure, and lung perfusion scintigraphy showed multiple low blood stream areas. Suspecting some endovascular abnormality, we performed immunohistochemical staining of the kidney biopsy specimen taken previously to find that endocapillary infiltrating cells were CD20-positive B lymphocytes. The infiltrating cells were confined to the endocapillary compartment in glomeruli and peritubular capillaries. Both clinical and pathological findings led us to diagnose intravascular large B cell lymphoma (IVLBCL). Two bone marrow biopsies and random skin biopsies were performed, but no abnormality was found. The present case demonstrates that clinical course and renal biopsy findings of intravascular large B cell lymphoma may mimic other renal conditions and that the identification of cell types with immunohistochemical staining may help establish an accurate diagnosis.
2012Relationship between parathyroid hormone and depression in heart failure.Arq Bras CardiolDepression has been found to be a predictor of rehospitalization and mortality in heart failure (HF). Parathyroid hormone (PTH) is a novel promising biomarker that can predict hospitalization, functional status and mortality in HF.We aimed to investigate the association of depression with serum PTH levels in patients with systolic HF.A total of consecutive 100 outpatients with systolic HF having left ventricular ejection fraction (LVEF) < 40%, were prospectively studied. All patients underwent laboratory tests, including brain natriuretic peptide (BNP) and PTH analyses. The patients were asked to complete the Beck Depression Inventory- II (BDI).Fifty-one patients (51%) were shown to have poor BDI score (BDIS > 18). Patients with poor BDI score had significantly higher PTH levels compared to those with good BDIS (133 ± 46 pg/ml vs. 71 ± 26 pg/ml, p < 0.001). In multivariable logistic regression model, PTH level (Odds ratio (OR) = 1.035, p = 0.003), LVEF (OR = 0.854, p = 0.004), NYHA functional class III/IV (OR = 28.022, p = 0.005), C-reactive protein (CRP) (OR = 1.088, p = 0.020), and presence of pretibial edema (OR = 12.341, p = 0.033) were found to be independent predictors of moderate to severe depression after adjustment of other potential confounders.Systolic HF patients with moderate to severe depression had higher serum levels of PTH and CRP, poor functional status and lower LVEF. The association of depression with such parameters might explain the contribution of depression to hospitalization and mortality in HF.
2013Therapeutic efficacy of tocilizumab in patients with rheumatoid arthritis refractory to anti-tumor-necrosis-factor inhibitors: 1 year follow-up with low-field extremity MRI.Mod RheumatolTocilizumab (TCZ) is effective in patients with rheumatoid arthritis (RA) who are refractory to anti-tumor-necrosis-factor (anti-TNF) biologics. The Rheumatoid Arthritis Society Disease Activity Score in 28 Joints (DAS28) is used to evaluate the response to TCZ. However, DAS28 is inappropriate marker because TCZ normalizes C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the early stage of treatment. The aim of our study was to test the usefulness of magnetic resonance imaging (MRI)-based markers of response to TCZ treatment.Nine patients with RA who were refractory to anti-TNF inhibitors (six to infliximab, one to etanercept, one to adalimumab, and one to both) were assessed. MRI images of both hands were obtained by low-field extremity MRI at baseline, 20, and 44 weeks of treatment, in addition to assessment with DAS28-ESR. The effect of TCZ on RA was examined by compact MRI score (cMRIS).All patients showed good or moderate response to TCZ treatment, as evaluated by significant reduction in DAS28-ESR at both 20 and 44 weeks (p < 0.001, each, relative to baseline). In contrast, MRI-based indexes (e.g., cMRIS, synovitis, edema, erosion scores) improved significantly at 44 weeks but not at 20 weeks.Differences in response to TCZ therapy were determined based on the method of evaluation, suggesting that MRI-based markers are potentially useful for evaluating RA response to TCZ therapy.
2012Fluid management in critically ill patients: the role of extravascular lung water, abdominal hypertension, capillary leak, and fluid balance.Ann Intensive CareCapillary leak in critically ill patients leads to interstitial edema. Fluid overload is independently associated with poor prognosis. Bedside measurement of intra-abdominal pressure (IAP), extravascular lung water index (EVLWI), fluid balance, and capillary leak index (CLI) may provide a valuable prognostic tool in mechanically ventilated patients.We performed an observational study of 123 mechanically ventilated patients with extended hemodynamic monitoring, analyzing process-of-care variables for the first week of ICU admission. The primary outcome parameter was 28-day mortality. ΔmaxEVLWI indicated the maximum difference between EVLWI measurements during ICU stay. Patients with a ΔmaxEVLWI <-2 mL/kg were called 'responders'. CLI was defined as C-reactive protein (milligrams per deciliter) over albumin (grams per liter) ratio and conservative late fluid management (CLFM) as even-to-negative fluid balance on at least two consecutive days.CLI had a biphasic course. ΔmaxEVLWI was lower if CLFM was achieved and in survivors (-2.4 ± 4.8 vs 1.0 ± 5.5 mL/kg, p = 0.001; -3.3 ± 3.8 vs 2.5 ± 5.3 mL/kg, p = 0.001, respectively). No CLFM achievement was associated with increased CLI and IAPmean on day 3 and higher risk to be nonresponder (odds ratio (OR) 2.76, p = 0.046; OR 1.28, p = 0.011; OR 5.52, p = 0.001, respectively). Responders had more ventilator-free days during the first week (2.5 ± 2.3 vs 1.5 ± 2.3, p = 0.023). Not achieving CLFM and being nonresponder were strong independent predictors of mortality (OR 9.34, p = 0.001 and OR 7.14, p = 0.001, respectively).There seems to be an important correlation between CLI, EVLWI kinetics, IAP, and fluid balance in mechanically ventilated patients, associated with organ dysfunction and poor prognosis. In this context, we introduce the global increased permeability syndrome.
2012Acute pancreatitis in aging animals: loss of pancreatitis-associated protein protection?World J GastroenterolTo investigate the effect of age on severity of acute pancreatitis (AP) using biochemical markers, histology and expression of the protective pancreatitis-associated proteins (PAPs).AP was induced via intraductal injection of 4% sodium taurocholate in young and old rats. Sera and pancreata were assayed at 24 h for the parameters listed above; we also employed a novel molecular technique to assess bacterial infiltration using polymerase chain reaction to measure bacterial genomic ribosomal RNA.At 24 h after induction of AP, the pancreata of older animals had less edema (mean ± SE histologic score of young vs old: 3.11 ± 0.16 vs 2.50 ± -0.11, P < 0.05), decreased local inflammatory response (histologic score of stromal infiltrate: 3.11 ± 0.27 vs 2.00 ± 0.17, P < 0.05) and increased bacterial infiltration (174% ± 52% increase from sham vs 377% ± 4%, P < 0.05). A decreased expression of PAP1 and PAP2 was demonstrated by Western blotting analysis and immunohistochemical staining. There were no differences in serum amylase and lipase activity, or tissue myeloperoxidase or monocyte chemotactic protein-1 levels. However, in the most-aged group, serum C-reactive protein levels were higher (young vs old: 0.249 ± 0.04 mg/dL vs 2.45 ± 0.68 mg/dL, P < 0.05).In older animals, there is depressed PAP expression related to a blunted inflammatory response in AP which is associated with worsened bacterial infiltration and higher C-reactive protein level; this may explain the more aggressive clinical course.
2012[Clinical analysis of children with severe hand-foot-and-mouth disease in Shanghai].Zhonghua Er Ke Za ZhiTo retrospectively analyzed the clinical features and epidemiology of children with severe hand-foot-and-mouth disease during 2009 and 2010 in Shanghai to investigate some risk factors with fatal cases.All the clinical records and laboratory results of serious patients were collected. A retrospective study was performed.A total of 748 serious patients were enrolled into this study, and the ratio of male to female was about 1.7:1; 724 patients were categorized into stage 2 with 254 patients in 2009 and 470 in 2010; 24 patients were categorized into stage 3 with 17 in 2009 and 7 in 2010. The rate of severity in 2010 (1.5%) was lower than in 2009 (6.3%) (χ2=12.836, P<0.01). Seven patients of stage 3 died, with the fatality 29.2%, which was higher than in stage 2 (P<0.01). The children aged between 3 months 10 days to 12 years 9 months with onset median age of 25 months. Among them, 77.1% patients aged between 1 and 4 years which also accounted for 79.2% of the fatal cases (19/24). But there was no significant difference between the age and the severity (χ2=0.804, P>0.05). Fever (100%), vomiting (57.0%) and myoclonus jerk (62.3%) were the most frequent symptoms occurred in those serious cases. The average period of fever in children of stage 2 and 3 was (4.10±1.40) d and (5.05±1.05) d, respectively, which indicated significant difference between the two groups (t=3.173, P<0.05). The average values of white-blood-cell counts and blood glucose in fatal patients were (14.8±6.25)×10(9)/L and (8.63±3.51) mmol/L. They were higher when compared to those in stage 2 with the white-blood-cell counts of (11.8±4.23)×10(9)/L and blood glucose of (5.51±2.14) mmol/L (P<0.05). But there was no significant difference in C-reactive protein or cerebrospinal fluid white-blood-cell counts; A total of 182 patients were enrolled for MRI study during the acute stage with 37 (37/182, 20.3%) presented abnormal findings. Among them, most frequent findings were hyperintense lesions seen in brain stem (11 cases). A stage 3 case who died presented brain edema on MRI examination.The epidemic of HFMD has some correlation with the area, season, health condition of the family and gender of the children. Children under 4 years of age especially those who lived in rural areas were susceptible to the HFMD. Frequent vomiting or myoclonus jerk may indicate the central nervous system involvement. But persistent high fever may indicate tendency to deteriorate. Some laboratory examinations can help find the fatal cases at an early time.
2012[Caecal ligation and puncture in the minipig - a model of sepsis induction].Cas Lek CeskSepsis belongs among the most serious conditions and animal models of sepsis are the basic tools to investigate the pathophysiological response to this condition.A total of 16 adult minipigs with identical baseline parameters were randomized into two groups. In the sepsis group (n = 10), sepsis was induced using caecal ligation and puncture (CLP). The control group (n = 6) underwent laparotomy without CLP. Selected clinical and laboratory parameters as well as histological findings between the sepsis and control group were subsequently compared.All animals undergoing CLP developed diffuse peritonitis and sepsis. Compared to the control group, experimental animals showed significant increase of body temperature and heart rate (while) requiring noradrenaline to maintain their perfusion pressure. No significant differences in the monitored biochemical parameters (including C-reactive protein levels) between the two groups were found. Histological findings in organs of experimental animals were consistent with changes of organs seen in sepsis, i.e., centrilobular liver necroses, acute tubular renal necrosis, serous fibrinopurulent exudate, myocardial malacias, and pulmonary edema.Experimental caecal ligation with a predefined size of the perforation in the intestinal wall is a suitable model for assessing the pathophysiological changes occurring in the body in sepsis.
2012Petechiae/purpura in well-appearing infants.Pediatr Emerg CareWell infants with petechiae and/or purpura can present to emergency departments, and their management can be difficult. Many will have extensive investigations and treatment that may not be necessary.This was a retrospective and descriptive audit investigating well infants (<8 months of age) presenting with petechiae or purpura in the absence of fever to a pediatric emergency department over a 9½-year period. All presenting problems of petechiae or purpura were reviewed. Patients were excluded if they appeared unwell, were febrile or have a history of fever, or had eccyhmoses on presentation.Thirty-six babies were identified. The average age was 3.8 months (range, 1-7 months). The majority of the infants had localized purpura/petechiae to the lower limbs (92%) with two thirds of these patients having bilateral signs. None had generalized signs. Most infants had a full blood count (94%), coagulation profile (59%) and C-reactive protein (59%), and blood cultures (59%), with all being normal (except for mild elevation in platelets). Nine patients were admitted for observation, with only 1 patient having progression of signs. This patient had a diagnosis of acute hemorrhagic edema of infancy. The rest of the patients were thought to have either a mechanical reason for their petechiae/purpura (tourniquet phenomena) or a formal diagnosis was not specified.Well infants with localized purpura and/or petechiae with an absence of fever are more likely to have a benign etiology. Further study is required to determine if a full blood count and coagulation profile is necessary, or a period of observation (4 hours) is all that is required. If there is no progression of signs, it is likely that they can be safely discharged. The likely cause may be due to a tourniquet phenomenon (eg, diaper).
2012Nonarteritic anterior ischemic optic neuropathy and double thrombophilic defect: a new observation.Case Rep OphthalmolWE REPORT THE FIRST CASE OF NONARTERITIC ANTERIOR ISCHEMIC NEUROPATHY (NAION) ASSOCIATED WITH DOUBLE THROMBOPHILIA: protein S deficiency and prothrombin G20210A mutation. A 58-year-old man is presented including the clinical and laboratory findings, cardiovascular profile and thrombophilia screening. The patient presented with 3/10 vision and an inferior altitudinal defect in the right eye. Funduscopic examination of the right eye revealed a hyperemic optic disk with blurred superior optic disk border and sectoral nerve fiber layer edema. Complete blood count, erythrocyte sedimentation rate and C-reactive protein were normal, suggesting a NAION. A workup of cardiovascular risk factors revealed hyperlipidemia, arterial hypertension and high-risk asymptomatic coronary artery disease. Due to the family history of deep vein thrombosis in the patient's daughter, a thrombophilia screening was additionally performed. The results revealed a double thrombophilic defect, namely congenital protein S deficiency and heterozygosity for prothrombin G20210A mutation, which were also identified in the patient's daughter. Anticoagulant warfarin therapy was initiated and the patient underwent a triple bypass surgery. At three-month follow-up, the right optic disk edema had resolved, leaving a pale superior optic nerve head. Visual acuity in the right eye had slightly improved to 4/10; however, the dense inferior altitudinal field defect had remained unchanged. The patient is currently treated with warfarin, atorvastatin, irbesartan and metoprolol. This case suggests that the first line of investigation in all patients with NAION involves assessment of cardiovascular risk factors. However, careful history taking will identify NAION patients who are eligible for additional thrombophilia screening: young patients without vasculopathic risk factors, bilateral or recurrent NAION, idiopathic or recurrent venous thromboembolism (VTE), positive family history of VTE, and VTE in young age or in unusual sites (e.g. cerebral, hepatic, mesenteric, or renal vein).
2012Efficacy of a high-dose in addition to daily low-dose vitamin A in children suffering from severe acute malnutrition with other illnesses.PLoS OneEfficacy of high-dose vitamin A (VA) in children suffering from severe acute malnutrition (SAM) has recently been questioned. This study compared the efficacy of a single high-dose (200,000 IU) in addition to daily low-dose (5000 IU) VA in the management of children suffering from SAM with diarrhea and/or acute lower respiratory tract infection (ALRI).In a randomized, double-blind, controlled clinical trial in icddr,b, Bangladesh during 2005-07, children aged 6-59 months with weight-for-height <-3 Z-score and/or bipedal edema (SAM) received either a high-dose VA or placebo on admission day. Both the groups received 5,000 IU/day VA in a multivitamins drop for 15 days and other standard treatment which is similar to WHO guidelines.A total 260 children (130 in each group) were enrolled. All had diarrhea, 54% had concomitant ALRI, 50% had edema, 48.5% were girl with a mean±SD age of 16±10 months. None had clinical signs of VA deficiency. Mean±SD baseline serum retinol was 13.15±9.28 µg/dl, retinol binding protein was 1.27±0.95 mg/dl, and pre-albumin was 7.97±3.96 mg/dl. Median (inter quartile range) of C-reactive protein was 7.8 (2.1, 22.2) mg/L. Children of the two groups did not differ in any baseline characteristic. Over the 15 days treatment period resolution of diarrhea, ALRI, edema, anthropometric changes, and biochemical indicators of VA were similar between the groups. The high-dose VA supplementation in children with SAM did not show any adverse event.Efficacy of daily low-dose VA compared to an additional single high-dose was not observed to be better in the management of children suffering from SAM with other acute illnesses. A single high-dose VA may be given especially where the children with SAM may leave the hospital/treatment center early.ClinicalTrials.gov NCT00388921.
2013Prevalence and significance of the MEFV gene mutations in childhood Henoch-Schönlein purpura without FMF symptoms.Rheumatol IntFamilial Mediterranean fever (FMF) has been reported more frequently in patients presenting with Henoch-Schönlein purpura (HSP) than in the general population. But, there is no clear knowledge about MEFV mutations in patients with HSP. We investigated the prevalence of MEFV mutations in children with HSP and without FMF whether these mutations have any effect on the disease course or complications. A total of 76 children with HSP who had no typical symptoms of FMF were screened for the mutations in exon 2 and exon 10 of the MEFV gene. Eleven of 76 patients (14.4 %) were heterozygous (E148Q in 5, M694V in 4, M680I in 1, E148V in 1), 5 (6.6 %) were homozygous (M694V/M694V in 4, V726A/V726A in 1), and 2 (2.6 %) were compound heterozygous (E148Q/M694V mutations in 1 and L110P/E148Q mutations in 1). Altogether, 7 patients carried 2 mutated MEFV alleles (9.2 %), which was higher than that observed in the general Turkish population (1 %). No significant differences in joint, gastrointestinal, renal involvement, or subcutaneous edema, and also acute phase reactants including leukocyte count, erythrocyte sedimentation rate, and serum C-reactive protein concentration were found between the groups. The prevalence of the two allele-MEFV mutations in patients with HSP was found higher than that of the general population. However, it seems that MEFV gene mutations may not have any effect on the clinical presentation of HSP.
2012Remitting seronegative symmetrical synovitis with pitting edema syndrome in a chronic hemodialysis patient.Case Rep MedA 75-year-old male who was undergoing chronic hemodialysis developed abrupt-onset pitting edema and pain in the dorsum of both hands and feet. Biochemical analysis disclosed increased C-reactive protein, and negative rheumatoid factor and antinuclear antibody. Radiological examination showed no bony erosion. Computed tomography and gallium scintigraphy revealed no active infection or neoplasms. The clinical diagnosis was remitting seronegative symmetrical synovitis with pitting edema (RS(3)PE) syndrome. The pitting edema and inflammatory response quickly subsided after low-dose prednisolone therapy. This case demonstrates that RS(3)PE syndrome could be a differential diagnosis in elderly patients undergoing dialysis who develop pitting edema and joint pain.
2012The time-averaged inflammatory disease activity estimates the progression of erosions in MRI of the sacroiliac joints in ankylosing spondylitis.Clin RheumatolA method to estimate the individual ankylosing spondylitis (AS) patient radiological progression of semi-quantitative magnetic resonance imaging (MRI) changes in the sacroiliac joints has not been described yet, which this study examines. Inflammatory disease activity and MRIs of the sacroiliac joints of 38 patients with recent onset established AS were analyzed at baseline and during follow-up. Sacroiliac MRIs were semi-quantitatively assessed using a modification of the "Spondylarthritis Research Consortium of Canada" (SPARCC) method. In each patient, the annual inflammatory disease activity was estimated by the time-averaged C-reactive protein (CRP; mg/l), calculated as the area under the curve. The mean (SD) CRP decreased from 1.3 (1.8) at baseline to 0.5 (0.6) at follow-up MRI (p < 0.04), which has been performed after a mean (SD) disease course of 2.8 (1.5) years. The mean (SD) annual increase (∆) of SPARCC score from baseline to follow-up MRI was 0.4 (0.4). Baseline individual SPARCC sub-score for bone marrow edema did not statistically significantly correlate with individual ∆SPARCC sub-score for erosions (p = N.S.). The individual AS patient correlation between annual time-averaged inflammatory disease activity and each annual ∆SPARCC sub-scores was only statistically significant for erosions (p < 0.01; r = 0.71). Our results show that bone marrow edema and contrast-medium enhancement at baseline do not relate to the progression of erosions but the calculation of the individual patient annual time-averaged inflammatory disease activity allows to estimate the annual progression of erosions in sacroiliac MRIs of patients with AS.
Twelve weeks of pioglitazone therapy significantly attenuates dysmetabolism and reduces inflammation in continuous ambulatory peritoneal dialysis patients--a randomized crossover trial.Perit Dial IntThe aim of the present study was to investigate the effect of oral pioglitazone (PIO) on lipid metabolism, insulin resistance, inflammation, and adipokine metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients.In this randomized crossover trial, 36 CAPD patients with serum triglyceride levels above 1.8 mmol/L were randomly assigned to receive either oral PIO 15 mg once daily or no PIO for 12 weeks. Then, after a 4-week washout, the patients were switched to the alternative regimen. The primary endpoint was change in serum triglycerides during the PIO regimen compared with no PIO. Secondary endpoints included changes in other lipid levels, homeostatic model assessment of insulin resistance (HOMA-IR), adipocytokines, and C-reactive protein (CRP).All 36 CAPD patients (age: 64 ± 11 years; 33% men; 27.8% with diabetes mellitus) completed the study. Comparing patients after PIO and no PIO therapy, we found no significant differences in mean serum triglycerides (3.83 ± 1.49 mmol/L vs 3.51 ± 1.98 mmol/L, p = 0.2). However, mean high-density lipoprotein (0.94 ± 0.22 mmol/L vs 1.00 ± 0.21 mmol/L, p = 0.004) and median total adiponectin [10.34 μg/mL (range: 2.59 - 34.48 μg/mL) vs 30.44 μg/mL (3.47 - 93.41 μg/mL), p < 0.001] increased significantly. Median HOMA-IR [7.51 (1.39 - 45.23) vs 5.38 (0.97 - 14.95), p = 0.006], mean fasting blood glucose (7.31 ± 2.57 mmol/L vs 6.60 ± 2.45 mmol/L, p = 0.01), median CRP [8.78 mg/L (0.18 - 53 mg/L) vs 3.50 mg/L (0.17 - 26.30 mg/L), p = 0.005], and mean resistin (32.70 ± 17.17 ng/mL vs 28.79 ± 11.83 ng/mL, p = 0.02) all declined. The PIO was well tolerated, with only one adverse event: lower-extremity edema in a patient with low residual renal function.Blood triglycerides were not altered after 12 weeks of PIO 15 mg once daily in CAPD patients, but parameters of dysmetabolism were markedly improved, including insulin resistance, inflammation, and adipokine balance, suggesting that PIO could be of value for this high-risk patient group. Larger, more definitive studies are needed to confirm these findings.
2012Early undernutrition is associated with attenuated inflammatory response and alteration in pharmacological efficacy of indomethacin in rats.Eur J Pharm SciThe intent of this study is to examine whether intrauterine malnutrition provokes alterations in the progression of the acute and subchronic inflammatory response, and its influence on the pharmacological effect of indomethacin.Rat offspring of dams which were fed from the first day of their gestation to term receiving a balanced diet (Labina) or a basic regional diet (BRD) from northeastern Brazil. According to their dams, the offspring were divided in two groups: Control-N (nourished) and BRD-g (undernourished during gestation). At 2 months of age, the animals were divided into groups (n=06): (1) Animals that were subjected to carrageenan or (2) zymosan-induce paw edema (acute inflammation models) and (3) Animals that were subjected to cotton pellet-induced granuloma (subchronic inflammation model). All animals received (saline 0.9%; p.o.). Another set of adult offspring was submitted to the same procedure as above, but instead of saline they received (via gavage) a single oral dose of indomethacin (10mg/kg) for the animals subjected to acute inflammation models or 2mg/kg for seven consecutive days for the animals subjected to subchronic inflammation model. The animals were further divided in two groups: Control-NI (Control-N treated with indomethacin), and BRDI-g (BRD-g treated with indomethacin). The volume of hind paw swelling (mL) was measured at time zero (before), 30, 60, 120, 180 and 240 min after carrageenan or zymosan injection. In the subchronic model of inflammation, the pellets were removed and dried to a constant weight. Hind paw swelling, weight of granuloma, blood albumin and C-reactive protein (CRP) levels, leukocyte count and cytokine levels were evaluated as indicators of inflammation.Undernutrition during pregnancy caused fetal growth retardation which was shown in terms of low birth weight (5.38±0.28), when compared to the Control-N (7.26±0.64) group. The volume of paw edema, the serum levels of CRP and albumin and cytokine levels were lower than those in the BRD-g group when compared to those in the Control-N groups, in both models of acute inflammation studied. However, no difference was found in the total leukocyte count. When compared to the respective groups treated with saline (Control-N and BRD-g), the antiinflammatory effect of indomethacin in the animals of BRDI-g groups was lower than in the Control-NI groups, in the model of acute inflammation. In the model of subchronic inflammation, the pharmacological effect of indomethacin was effective only in nourished animals.Malnutrition in the early stages of development attenuated the severity of the acute inflammatory response, but there was no statistically significant change in subchronic inflammation induced by granulomatous lesion. Our findings provide impetus for larger trials to assess the influence of undernutrition on the pharmacokinetics/pharmacodynamics of indomethacin.
2012Eleven cases of angioedema with eosinophilia treated in a single hospital in Japan.Allergol IntAngioedema with eosinophilia (AE) is mostly reported in Japanese patients, and only as case reports. In this study, we aimed to determine how prevalent AE cases appear, the characteristic features and the course of AE, and to evaluate whether corticosteroid therapy for AE is necessary or not.The patients whose blood samples showed an eosinophil count of ≥2,000/μL, among the samples tested for blood cell counts and differential counts between January 2006 and December 2010, in Japanese Red Cross Medical Center, were firstly included. Among these, patients with AE were extracted.All of the 11 patients were Japanese young females. One patient with arthralgia showed radioisotope accumulation in the joints by bone scintigraphy. The peak peripheral blood eosinophil count was 7,839 ± 6,008 (2,130-23,170)/μL after visiting our hospital. An increase in white blood cell count was only due to an increase in eosinophil count. Serum C-reactive protein and IgE levels remained almost normal. Peripheral blood eosinophil count decreased steadily for 8 weeks, regardless of corticosteroid use. Edema in all of the patients and arthralgia in 6 patients improved within 12 weeks. As far as followed, none of the patients had a recurrence of AE.AE developed in Japanese young females and likely showed a single course. In AE, the count of eosinophil of 104/μL was observed. Only eosinophil count increased among leukocyte series. Serum C-reactive protein and IgE levels remained almost normal. The eosinophil count in AE patients will return to the normal level within 8 weeks even without corticosteroid therapy.
2012Anti-arthritis activity of roots of Hemidesmus indicus R.Br. (Anantmul) in rats.Asian Pac J Trop MedTo investigate the protective effects of hydroalcoholic and its fractions from roots of Hemidesmus indicus on arthritis in in vitro models of rodents.Preliminary phytochemical analysis and thin-layer chromoatography were performed to analyze constituents of hydroalcoholic extract and its three fraction namely ethyl acetate fraction, chloroform fraction and residual fraction of root of Hemidesmus indicus. Arthritis rats models were established by Complete Freund's Adjuvant. The parameters including paw edema, body weight, arthritic index, erythrocyte sedimentation rate, serum rheumatoid factor, serum C-reactive protein, serum nitrite level, and histopathology of synovial joints were observed. Methotrexate was taken as positive control.Rats treated with hydroalcoholic extract (450 mg/kg, p.o.), ethyl acetate (75 mg/kg, p.o.), chloroform (60 mg/kg, p.o) and residual fractions (270 mg/kg, p.o.), showed significant decrease in physical and biochemical parameters compared with arthritic model rats. Hydroalcoholic extract and its ethyl acetate fraction of Hemidesmus indicus showed significantly higher anti-arthritic activity than chloroform and residual fraction. Histopathological analysis demonstrated that both of hydroalcoholic extract and its ethyl acetate fraction had comparable anti-arthritic activity with methotrexates.The present study suggests that Hemidesmus indicus has protective activity against arthritis and the activity might be attributed to presence of terpenoid in hydroalcoholic extract, as well as in ethyl acetate fraction.
2012The effects of the combination of sodium ferulate and oxymatrine on lipopolysaccharide-induced acute lung injury in mice.InflammationIn our previous study, the remarkable analgesic and anti-inflammatory effects of the combination of sodium ferulate (SF) and oxymatrine (OMT) had been found. In this study, we investigated the effect of the combination of SF and OMT on acute lung injury using lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The cell counting and the protein concentration in the bronchoalveolar lavage fluid (BALF) were measured. The animal lung edema degree was evaluated by wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators including C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were assayed by enzyme-linked immunosorbent assay method. The data showed that treatment with the combination of SF and OMT markedly attenuated inflammatory cell numbers and protein concentration in the BALF and improved SOD activity and inhibited MPO activity compared to LPS group. Moreover, the combination significantly inhibited the production of CRP and TNF-α in lung homogenate. The histological changes of the lungs were also more significantly improved by the combination. At the same dose, the obvious protective effect was not found in SF or OMT-treated alone group except that the protein concentration slightly decreased in SF group. The results indicated that the combination SF and OMT had a protective effect on LPS-induced ALI in mice, and the effect was much better than that of SF or OMT used alone.
2011Glutaraldehyde-induced colitis: case reports and literature review.Kaohsiung J Med SciGlutaraldehyde-induced colitis is an uncommon colitis in clinical practice. Because the involvement of colonic segment is determined by the endoscopic part where glutaraldehyde remains, a recent history of endoscopy and a demarcated involvement of colonic segment are the most characteristic signs of glutaraldehyde-induced colitis. The typical clinical scenario is acute onset of lower abdominal pain, fever, and bloody stool. Laboratory data usually show leukocytosis and elevated C-reactive protein. The endoscopic pictures of involved segments are compatible with acute colitis, including hyperemic, edematous, with or without multiple erosions. Acute ischemic colitis and infectious colitis should be differentiated at the outset of the disease. Stool pathogen tests are usually negative. Parenteral empiric antibiotic may be considered if severe transmural edema of the involved segment is observed in computed tomography. Conservative treatment, including bowel rest and parenteral hydration, is able to stabilize the condition in a week. Herein, we present two cases of acute proctocolitis caused by glutaraldehyde after uneventful colonoscopy.
2012Deferoxamine attenuates lipid peroxidation, blocks interleukin-6 production, ameliorates sepsis inflammatory response syndrome, and confers renoprotection after acute hepatic ischemia in pigs.Artif OrgansWe have previously shown that deferoxamine (DFO) infusion protected myocardium against reperfusion injury in patients undergoing open heart surgery, and reduced brain edema, intracranial pressure, and lung injury in pigs with acute hepatic ischemia (AHI). The purpose of this research was to study if DFO could attenuate sepsis inflammatory response syndrome (SIRS) and confer renoprotection in the same model of AHI in anesthetized pigs. Fourteen animals were randomly allocated to two groups. In the Group DFO (n=7), 150mg/kg of DFO dissolved in normal saline was continuously infused in animals undergoing hepatic devascularization and portacaval anastomosis. The control group (Group C, n=7) underwent the same surgical procedure and received the same volume of normal saline infusion. Animals were euthanized after 24h. Hematological, biochemical parameters, malondialdehyde (MDA), and cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α) were determined from sera obtained at baseline, at 12h, and after euthanasia. Hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling were used to evaluate necrosis and apoptosis, respectively, in kidney sections obtained after euthanasia. A rapid and substantial elevation (more than 100-fold) of serum IL-6 levels was observed in Group C reaching peak at the end of the experiment, associated with increased production of oxygen free radicals and lipid peroxidation (MDA 3.2±0.1nmol/mL at baseline and 5.5±0.9nmol/mL at the end of the experiment, P<0.05) and various manifestations of SIRS and multiple organ dysfunction (MOD), including elevation of high-sensitivity C-reactive protein, severe hypotension, leukocytosis, thrombocytopenia, hypoproteinemia, and increased serum levels of lactate dehydrogenase (fourfold), alkaline phosphatase (fourfold), alanine aminotransferase (14-fold), and ammonia (sevenfold). In sharp contrast, IL-6 production and lipid peroxidation were completely blocked in DFO-treated animals offering remarkable resistance to the development of SIRS and MOD. Profound proteinuria, strips of extensive necrosis of tubular epithelial cells, and occasional apoptotic tubular epithelial cells were already present in Group C, but not in Group DFO animals at the time of euthanasia. DFO infusion attenuated lipid peroxidation, blocked IL-6 production, and substantially diminished SIRS and MOD, including tubulointerstitial damage in pigs after acute ischemic hepatic failure. This finding shows that iron, IL-6, and lipid peroxidation are important participants in the pathophysiology of renal injury in the course of generalized inflammation and provides novel pathways of therapeutic interventions for renal protection.
2013The effectiveness of Echinacea extract or composite glucosamine, chondroitin and methyl sulfonyl methane supplements on acute and chronic rheumatoid arthritis rat model.Toxicol Ind HealthThe study aimed to investigate the effect of the oral administration for 15 days of either Echinacea (E) or genuphil (a composite of chondroitin sulphate, glucosamine and methyl sulfonyl methane [GCM]) nutraceutical supplements on female rat model of acute or chronic arthritis induced by bacterial outer membrane protein (OMP) from faecal flora of healthy and rheumatic humans. Anti-cyclic citrullinated peptide (anti-CCP2), C-reactive protein (CRP) and rheumatoid factor (RF) values increased (p < 0.05) in both arthritic groups as compared to normal values. The rheumatic markers anti-CCP2, CRP and RF values decreased significantly in E- and GCM-treated groups compared to arthritic none-treated acute or chronic groups. The results of RF values of GCM-treated groups in acute and chronic models decreased exhibiting no statistical difference compared with the normal value. Histological examinations of the hind paw sections revealed moderate inflammation, oedema and mild proliferation of synovial cells in acute arthritic rats and more damage to cartilage and bone with severe inflammation in chronic ones. Echinacea acute treated group showed edema with proliferated synovial membrane and partial damage in cartilage and bone. While in the E-chronic treated group, rough edge with destructed cartilage and bone existed. However, the acute GCM group revealed mild cartilage damage. But the chronic GCM group showed mild synovial cells proliferation and revealed no inflammation with mild cartilage damage edge. Results demonstrated the OMP arthropathic property and through promising light on arthritis treatment using E- or GCM, with the advantage of GMC results over that of E-. The composite GCM is needed for further studies over the dose and duration to assess its preventive effects against the bacterial OMP arthrogenicity.
2012Anti-inflammatory and antioxidative effects of mucilage of Trigonella foenum graecum (Fenugreek) on adjuvant induced arthritic rats.Int ImmunopharmacolThe aim of this study was to investigate anti-inflammatory and antioxidant effects of mucilage from fenugreek in adjuvant induced arthritis in rats. Arthritis was induced by intradermal injection of complete Freund's adjuvant into the right hind paw produce inflammation of the joint. The activities of inflammatory enzymes like cyclooxygenase, lipoxygenase and myeloperoxidase, and levels of nitrite and C-reactive protein were observed. Also oxidative stress was measured by analyzing the activity of catalase, superoxide dismutase, glutathione peroxidase and the levels of glutathione and vitamin C and lipid peroxidation. The blood parameters like ESR, total WBC, RBC and hemoglobin content was checked. Fenugreek mucilage exhibited maximum percentage of edema inhibition at a dose of 75 mg/kg on 21st day of adjuvant arthritis. The effect was higher than that of standard drug indomethacin. The activities of cyclooxygenase-2 and myeloperoxidase and concentration of thiobarbituric acid reactive substance (TBARS) were decreased and the activities of antioxidant enzymes, vitamins C and reduced glutathione level were increased on treatment with fenugreek mucilage. The increment in ESR and total WBC, reduction in RBC count and hemoglobin and aberrant changes to the C-reactive protein (CRP) levels observed in the arthritic animals were also found to be significantly restored in fenugreek mucilage treated rats. Histopathology of paw tissue showed decreased edema formation and cellular infiltration on supplementation with fenugreek mucilage. Thus the results demonstrated the potential beneficiary effect of fenugreek mucilage on adjuvant induced arthritis in rats.
2012Adalimumab successful in sarcoidosis patients with refractory chronic non-infectious uveitis.Graefes Arch Clin Exp OphthalmolAdalimumab, a humanized monoclonal antibody targeted against TNF-α, has proved to be successful in the treatment of uveitis. Another anti-TNF-α agent, i.e., infliximab, has been reported of benefit in the treatment of refractory sarcoidosis. The aim of this prospective case series was to evaluate the effect of adalimumab on intraocular inflammatory signs and other relevant clinical manifestations (lung function, serological inflammatory parameters, and fatigue) of sarcoidosis.Sarcoidosis patients with refractory posterior uveitis (n = 26, 17 females, 41 eyes in total) were systematically followed for 12 months after initiation of adalimumab 40 mg sc once a week. Inclusion criteria were non-responsiveness to prednisone and methotrexate (MTX) or intolerance to these drugs. Adjunctive therapy with prednisone and MTX was tapered during treatment with adalimumab. Localization and improvement, stabilization or deterioration of intraocular inflammatory signs was scored. Pulmonary function- and laboratory testing were performed and Fatigue Assessment Scale was completed. Results at baseline, 6 months, and 12 months were compared.Choroidal involvement resolved in 10/15 patients, five had partial improvement; vasculitis resolved in 1/1 patient; papillitis resolved in 7/8 patients, one had partial response; macular edema resolved in 5/8 patients, three had partial response; vitreous cleared completely in 5/5 patients. Overall outcome regarding intraocular inflammatory signs showed improvement in 22 patients (85%) and stabilization in four patients (15%). At 12 months, no recurrences were reported in those successfully treated. Laboratory parameters of inflammatory activity (C-reactive protein; serum angiotensin-converting enzyme and soluble interleukin-2 Receptor) improved (p < 0.01). Moreover, fatigue improved in 14/21 (67%) of the patients suffering from fatigue and the diffusion capacity for carbon monoxide (DLCO) improved in 7/8 (88%) of patients with a decreased DLCO (p < 0.01). The dosage of both prednisone and MTX could be tapered down significantly (p < 0.01 and p < 0.05, respectively).Adalimumab appeared successful in sarcoidosis patients with refractory chronic non-infectious uveitis showing improvement in intraocular inflammatory signs as well as in other relevant clinical indicators of disease activity. Future randomized studies are needed to determine the optimal dosage, dose interval and duration of therapy in refractory multisystemic sarcoidosis.
2011Cytokine response to diabetic ketoacidosis (DKA) in children with type 1 diabetes (T1DM).Endocr JIt has been suggested that cytokine release during DKA may result in capillary perturbation and thus may contribute to the development of its acute clinical complications (i.e.cerebral or pulmonary edema). We studied in 38 newly diagnosed T1DM children with DKA, aged 7.68±3.07 years, plasma levels of cytokines IL-1β (interleukin-1β), IL-2, IL-6, IL-8, IL-10, TNF-α (tumour necrosis factor-α) and also WBC (white blood cell count), hs-CRP (high sensitivity C-reactive protein), GH (growth hormone) and cortisol, prior to, during and 120h after DKA management, with the aim to monitor their levels at different time-points and in different degrees of DKA severity. Prior to DKA management the levels of IL-6, IL-8, IL-10, WBC and cortisol were elevated, but were all reduced within 120 h after DKA management. Then the patients were divided into two groups: a. moderate/severe: pH≤7.2, b. mild DKA: pH>7.2. In the group with moderate/severe DKA (ph≤7.2), IL-10 levels were the highest of all cytokines, but were significantly decreased after 6h (91.76 vs 18.04 pg/mL, p=0.008), with no further change, while IL-6 levels were decreased at 120 h (28.32 vs 11.9 pg/mL, p=0.003). The above were not observed in the group with mild DKA. In conclusion, in the children with DKA of our study, in the group with moderate/severe DKA the IL-10 levels were prematurely reduced at 6 hours, while the IL-6 levels remained high and were reduced at 120 hours after the DKA management. These changes may be responsible for increased capillary perturbation, which could lead to the subsequent development of acute DKA complications.
2011[A case of fasciitis localized in the calf muscles associated with Edwardsiella tarda sepsis].Rinsho ShinkeigakuA 49-year-old man presented with fever and pain, redness, swelling, and difficulty in walking. The serum C-reactive protein (CRP), creatin kinase (CK), and endotoxin levels were elevated. A blood culture revealed Edwardsiella tarda(E. tarda). Computed tomography (CT) showed subfascial and subcutaneous low-density areas in the lower legs, suggesting focal abscesses and edema. The patient was likely to have necrotizing fasciitis or cellulitis. He was successfully treated with several antibiotics and discharged after 43 days. Because E. tarda causes sepsis and fulminating necrotizing fasciitis with a high mortality rate in patients with an underlying illness, it should be considered a potentially important pathogen. The lack of an underlying illness may be a factor for a good outcome in this case.
2011Synovitis and osteitis are very frequent in rheumatoid arthritis clinical remission: results from an MRI study of 294 patients in clinical remission or low disease activity state.J RheumatolIn rheumatoid arthritis (RA), radiographic progression may occur despite clinical remission. This may be explained by subclinical inflammation. Magnetic resonance imaging (MRI) provides a greater sensitivity than clinical examination and radiography for assessing disease activity. Our objective was to determine the MRI characteristics of RA patients in clinical remission or low disease activity (LDA) state.Databases from 6 cohorts were collected from 5 international centers. RA patients in clinical remission according to Disease Activity Score28-C-reactive protein (DAS28-CRP < 2.6; n = 213) or LDA-state (2.6 ≤ DAS28-CRP < 3.2; n = 81) with available MRI data were included. MRI were assessed according to the OMERACT RA MRI scoring system (RAMRIS).70% women, median age 55 (interquartile range, IQR 43-63) years, disease duration 2.3 (IQR 0.7-5.1) years, DAS28-CRP 2.2 (IQR 1.8-2.6), Simplified Disease Activity Index, SDAI, 3.9 (IQR 1.9-6.5), Clinical Disease Activity Index, CDAI, 3.1 (IQR 1.5- 5.8), rheumatoid factor/anti-cyclic citrullinated peptide positivity 57%/54%, presence of radiographic erosions: 66%. Wrist and metacarpophalangeal MRI (MCP-MRI) data were available for 287 and 241 patients, respectively. MRI inflammatory activity in wrist and/or MCP joints was observed in the majority [synovitis: 95%, bone edema (osteitis): 35%] of patients. The median (IQR) RAMRIS score was 6 (3-9) for synovitis and 0 (0-2) for osteitis. Synovitis and osteitis were not less frequent in DAS28 clinical remission (synovitis/osteitis 96%/35%) than LDA (91/36). A trend towards lower frequencies of osteitis in patients in SDAI and CDAI remission was observed.Subclinical inflammation was identified by MRI in the majority of RA patients in clinical remission or LDA state. This may explain structural progression in such patients. Further work is required to understand the place of modern imaging in future remission criteria.
2011The synergistic anti-inflammatory effect of the combination of sodium ferulate and oxymatrine and its modulation on inflammation-associated mediators in RAW 264.7 cells.J EthnopharmacolThe combination of Radix Angelicae sinensis (Oliv.) Diels and Radix Sophora flavescens Ait. was extensively used in traditional Chinese medicine to treat inflammatory diseases, such as acne, heart disease, and hepatitis. Sodium ferulate (SF) and oxymatrine (OMT) were effective component of Radix Angelicae sinensis (Oliv.) Diels and Radix Sophora flavescens Ait., respectively.In this study, we investigated the synergistic anti-inflammatory effect of the combination of SF and OMT, and its modulation on inflammation-associated mediators in RAW 264.7 cells.In vivo, the anti-inflammatory effects of the combination of SF and OMT were evaluated with the xylene-induced mouse ear edema model and the carrageenan-induced rat paw edema model. In vitro, chemokines and cytokines mRNA expressions in lipopolysaccharide (LPS)-activated RAW 264.7 cells were determined by real-time PCR (RT-PCR) microarray analysis. The levels of interleukin-11 (IL-11), C-reactive protein (CRP) and interferon-γ (INF-γ) in the supernatant of LPS-stimulated RAW 264.7 cells were measured by enzyme-linked immune-sorbent assay (ELISA).The combination of SF and OMT could significantly inhibit the edema in the xylene-induced mouse ear edema and carrageenan-induced rat paw edema, but no effect was found when each drug was used alone according to above doses. The combination exhibited a better effect in down-regulating mRNA expressions of inflammation-associated mediators in LPS-stimulated RAW 264.7 cells than SF or OMT alone. The ELISA results showed that the combination synergistically inhibited LPS-induced IL-11, CRP and INF-γ production in a dose-dependent manner.The combination of SF and OMT showed synergistic anti-inflammatory effect, and the activity was probably related to its modulation on inflammation-associated mediators, especially IL-11, CRP and INF-γ.
2012Rheumatoid arthritis complicated with immunodeficiency-associated lymphoproliferative disorders during treatment with adalimumab.Mod RheumatolA 71-year-old woman was diagnosed with rheumatoid arthritis in 2002. Treatment was started with methotrexate and she was switched to adalimumab in 2006. In May 2008, she started complaining of swelling of the left axilla and the left elbow lymph nodes, and adalimumab was discontinued in December. Her lymphadenopathy did not resolve and she was admitted to hospital with fever in May 2009. Subsequent laboratory examinations showed that serum alkaline phosphatase, gamma-glutamyl transpeptidase, C-reactive protein, and soluble interleukin-2 receptor levels were 3,078 IU/l, 510 IU/l, 20 mg/dl, and 7,290 U/ml, respectively. Gallium scintigraphy showed high-intensity areas in the above-mentioned lymph nodes. She suddenly progressed to jaundice and died of pulmonary edema on the 25th day of hospitalization. Autopsy indicated large atypical cells with a distorted nucleus that had multiplied in the above-mentioned lymph nodes. On immunohistochemical staining these cells showed positive staining for CD15, CD30, PAX-5, Epstein-Barr virus (EBV) early small RNA (EBER), and LMP-1. Reactivation of EBV was diagnosed via EBV antibodies and an EBV DNA determination. We considered that she had developed EBV-associated lymphoproliferative disorders due to immunodeficiency caused by adalimumab administration. Reactivation of EBV associated with adalimumab and the relationship of this reactivation to malignant lymphoma have been rarely reported.
2011Imatinib in active diffuse cutaneous systemic sclerosis: Results of a six-month, randomized, double-blind, placebo-controlled, proof-of-concept pilot study at a single center.Arthritis RheumTo better understand the feasibility of using imatinib, a tyrosine kinase inhibitor, to treat active diffuse cutaneous systemic sclerosis (dcSSc).We performed a 6-month, randomized, double-blind, placebo-controlled, proof-of-concept pilot study of imatinib in patients with active dcSSc. Data on safety, modified Rodnan skin thickness scores (MRSS), Health Assessment Questionnaire (HAQ) scores, patient's and physician's global assessments (100-mm visual analog scale), and biomarkers in serum and skin biopsy samples were collected. We used a 4:1 randomization strategy (imatinib 200 mg administered twice a day versus placebo), stratifying according to current use of methotrexate. The plan was to enroll 20 dcSSc patients.After enrolling 10 patients (9 receiving active drug and 1 receiving placebo), we found poor tolerability and high rates of adverse events with imatinib, and study enrollment was discontinued. There was no significant difference in the mean MRSS in all patients who took imatinib (31.1 at baseline versus 29.4 at 6 months) or in only those who completed 6 months of imatinib (31.0 at baseline versus 30.3 at 6 months), and there was no difference in the C-reactive protein level, erythrocyte sedimentation rate, physician's global assessment, patient's global assessment, response to the Health Transition query, or the HAQ scores between those who did and those who did not complete 6 months of therapy. Side effects were edema, fluid retention, fatigue, nausea, cramps/myalgias, diarrhea, alopecia, and anemia. Most side effects occurred within the first week of treatment, and even when imatinib was reintroduced at a lower dosage (200 mg daily), it was poorly tolerated. Two patients were hospitalized because of side effects of the medication. In general, biomarker levels in plasma and skin did not change.Imatinib was poorly tolerated, and this could limit its application in SSc. The study was too small to form conclusions about the efficacy of imatinib in SSc.
2011Association between symptoms of chronic venous disease in the lower extremities and cardiovascular risk factors in middle-aged women.Int AngiolThe association between chronic venous disease (CVD) and atherosclerosis has been intensively investigated. Because data regarding cardiovascular disease in women are sparse, we evaluated the potential association between the symptoms of CVD and cardiovascular risk factors including markers of preclinical atherosclerosis in middle-aged women.A questionnaire for chronic lower limb venous insufficiency was completed by 902 women, aged 45-54 years, from the general population. At the same time, all women were examined for the presence of cardiovascular risk factors, including the ankle/brachial systolic blood pressure index (ABI) and carotid intima media thickness of the common carotid arteries measured by ultrasound. Differences in cardiovascular risk factors and markers of preclinical atherosclerosis between women with and without symptoms of CVD were evaluated.Symptoms (cramps, aching, edema, disturbance of sleep) suggestive of CVD in the lower extremities were reported by 606 (67.2%) women and 114 (12.6%) reported that those symptoms were severe enough to limit their usual daily activities. A higher prevalence of ABI of less than 0.91 was observed in women with any (P=0.005) or severe (P=0.029) CVD symptoms. A significantly higher prevalence of the following were observed in women with any or severe CVD symptoms: coronary artery disease, history of diabetes mellitus, increased body mass index, waist circumference, serum triglycerides, serum C-reactive protein and lower serum HDL cholesterol.CVD symptoms were strongly associated with a higher prevalence of pathological values of ABI and several other manageable cardiovascular risk factors. These findings support the data that chronic venous disease might also indicate increased risk for atherosclerosis.
2012Analgesic and anti-inflammatory effects of ethyl acetate fraction of Polygonum cuspidatum in experimental animals.Immunopharmacol ImmunotoxicolPolygonum cuspidatum (PC) has been used for the treatment of arthritis and urinary diseases in traditional medicine. Despite recent evidence that PC has anti-oxidant, anti-tumoral, and anti-inflammatory effects, analgesic and anti-inflammatory effects of PC have not been elucidated yet in vivo. Thus, in the present study, analgesic and anti-inflammatory effects of ethyl acetate extract of PC (EAPC) were investigated in vivo for the first time. Hot plate test and tail-flick test revealed that EAPC at 200 mg/kg exerts analgesic effect (p < 0.05). In contrast, EAPC did not show significant analgesic effect in acetic acid-induced writhing test. Serotonin-induced paw edema model and Freund's complete adjuvant (FCA)-induced adjuvant arthritis model were used to examine anti-inflammatory effect of EAPC in vivo. In serotonin-induced paw edema model, EAPC suppressed swelling inflammatory response within 12 min after serotonin injection, at both 100- and 200-mg/kg dose (p < 0.05). Consistently, in FCA-induced adjuvant arthritis model, FCA at 200 mg/kg significantly suppressed FCA-induced joint swelling within 3 days (p < 0.05), whereas FCA at 100 mg/kg showed the similar result within 5 days (p < 0.05). Furthermore, EAPC effectively inhibited positive responses of c-reactive protein and rheumatoid factor compared to untreated control. Taken together, our findings suggest that EAPC can be a potent candidate for rheumatoid arthritis treatment.
2011Diagnostic utility of C-reactive protein combined with brain natriuretic peptide in acute pulmonary edema: a cross sectional study.Respir ResDiscriminating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) from cardiogenic pulmonary edema (CPE) using the plasma level of brain natriuretic peptide (BNP) alone remains controversial. The aim of this study was to determine the diagnostic utility of combination measurements of BNP and C-reactive protein (CRP) in critically ill patients with pulmonary edema.This was a cross-sectional study. BNP and CRP data from 147 patients who presented to the emergency department due to acute respiratory failure with bilateral pulmonary infiltrates were analyzed.There were 53 patients with ALI/ARDS, 71 with CPE, and 23 with mixed edema. Median BNP and CRP levels were 202 (interquartile range 95-439) pg/mL and 119 (62-165) mg/L in ALI/ARDS, and 691 (416-1,194) pg/mL (p < 0.001) and 8 (2-42) mg/L (p < 0.001) in CPE. BNP or CRP alone offered good discriminatory performance (C-statistics 0.831 and 0.887), but the combination offered greater one [C-statistics 0.931 (p < 0.001 versus BNP) (p = 0.030 versus CRP)]. In multiple logistic-regression, BNP and CRP were independent predictors for the diagnosis after adjusting for other variables.Measurement of CRP is useful as well as that of BNP for distinguishing ALI/ARDS from CPE. Furthermore, a combination of BNP and CRP can provide higher accuracy for the diagnosis.
2011Acute hemorrhagic edema of young children: a concise narrative review.Eur J PediatrAcute hemorrhagic edema of young children is an uncommon but likely underestimated cutaneous leukocytoclastic vasculitis. The condition typically affects infants 6-24 months of age with a history of recent respiratory illness with or without course of antibiotics. The diagnosis is made in children, mostly nontoxic in appearance, presenting with nonpruritic, large, round, red to purpuric plaques predominantly over the cheeks, ears, and extremities, with relative sparing of the trunk, often with a target-like appearance, and edema of the distal extremities, ears, and face that is mostly non-pitting, indurative, and tender. In boys, the lesions sometimes involve the scrotum and, more rarely, the penis. Fever, typically of low grade, is often present. Involvement of body systems other than skin is uncommon, and spontaneous recovery usually occurs within 6-21 days without sequelae. In this condition, laboratory tests are non-contributory: total blood cell count is often normal, although leukocytosis and thrombocytosis are sometimes found, clotting studies are normal, erythrocyte sedimentation rate and C-reactive protein test are normal or slightly elevated, complement level is normal, autoantibodies are absent, and urinalysis is usually normal. Experienced physicians rapidly consider the possible diagnosis of acute hemorrhagic edema when presented with a nontoxic young child having large targetoid purpuric lesions and indurative swelling, which is non-pitting in character, and make the diagnosis either on the basis of clinical findings alone or supported by a skin biopsy study.
Van neck disease: osteochondrosis of the ischiopubic synchondrosis.J Pediatr OrthopVan Neck disease (VND) is a benign skeletal abnormality of children involving a hyperostosis of the ischiopubic synchondrosis (IPS) seen on radiographs. Patients typically complain of vague groin or buttock pain. Few descriptions of this disorder exist and it easily can be mistaken for other entities, particularly osteomyelitis or tumor. It is often considered a diagnosis of exclusion as laboratory values are usually normal and routine radiographic workup may be nonspecific. We present a series of patients with VND and we compare them with a similar cohort of patients with acute hematogenous ischiopubic osteomyelitis (IPOM). We also draw attention to a new magnetic resonance imaging (MRI) finding that seems to support the theory that VND results from an excessive pull of the hamstring tendon on the ischial tuberosity.All patients presenting to our institution for the evaluation of groin or buttock pain during an 8-year period (August 2001 to May 2009) were retrospectively identified. Twenty-five patients demonstrated enhancement of the ischiopubic area on MRI. Five patients were excluded for lack of sufficient laboratory data. Ten patients were diagnosed and treated with culture proven IPOM and 10 patients were diagnosed with VND and treated with observation. History, physical examination, laboratory values, plain films, and MRI were compared to identify the diagnostic differences between these 2 entities.The age range for both groups was between 4 and 12 years old. The mean age was 7 years for the VND group and 7.6 years for the IPOM group. The VND group tended to have more distinct hyperostosis of the IPS on radiographs. The factors that were characteristic of IPOM were: fever, limp, pain with rotation of the hip, elevated erythrocyte sedimentation rate, elevated C-reactive protein (CRP), and positive blood culture. MRI showed obvious myositis, abscess, and free fluid surrounding the IPS in all patients with IPOM, but not in the VND patients. Enhancement was seen in the ischial tuberosity, near the hamstring origin, in nearly all Van Neck patients; this pattern of edema may support stress reaction and callus formation as a mechanism for IPS hypertrophy.VND is a little-known entity characterized by enlargement of the IPS and should be in the differential of groin or buttock pain in children from the age of 4 to 12 years. IPOM may present similar to VND. Absence of fever, limp, pain with rotation of the hip, elevated C-reactive protein/erythrocyte sedimentation rate, and negative blood culture can help to differentiate VND from IPOM. Presence of marrow edema around the IPS and in the ischial tuberosity, along with absence of surrounding myositis, abscess, and free fluid on MRI are reliable findings that can confirm the diagnosis of VND. The absence of these characteristics can eliminate the need for admission, aspiration, or biopsy. The treatment for VND is observation and the symptoms should abate over time with expectant management.Comparative Diagnostic, Level IV.
2011Treatment of small hepatocellular carcinomas with US-guided high-intensity focused ultrasound.Ultrasound Med BiolHigh-intensity focused ultrasound (HIFU) is a noninvasive method that can cause complete coagulation necrosis without requiring the insertion of any instruments. The purpose of this study was to evaluate the safety and efficacy of HIFU treatment for small liver cancers without performing transcatheter arterial chemoembolization (TACE) or rib resection. HIFU ablation was performed without rib resection or the aid of TACE or percutaneous ethanol injection (PEI) in 12 patients with hepatocelullar carcinoma. The HIFU system (Chongqing Haifu Tech, Chongqing, China) was used under ultrasound guidance. All 12 patients completed the treatment without experiencing any adverse events. Complete coagulation was achieved by applying the sonications from the intercostal space when the tumor was located in the right lobe. After treatment, serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) levels were significantly higher than the baseline values; these levels recovered within 1 week. C-reactive protein (CRP) levels increased 1 week after treatment but decreased within 1 month. An epidural anesthetic provided sufficient pain suppression during the procedure. Edema of the subcutaneous tissue was detected in five cases, but the edema disappeared within 1 month. None of the patients developed acute hepatic failure, liver abscess or renal dysfunction. In conclusion, HIFU is effective for the treatment of patients with small liver cancer.
2011[Chronic renal failure: unexpected late sequela of pulmonary tuberculosis after 30 years].Mikrobiyol BulTuberculosis-related chronic granulomatous tubulointerstitial nephritis (GTN) and chronic renal dysfunction as a consequence of GTN is a rarely seen clinical condition, with a few case reports in the literature. In this report, a case with end stage renal failure as an unexpected late extrapulmonary sequela of tuberculosis has been presented. A 60 years old female patient was admitted to hospital with the complaints of fever, malaise and nausea. Her history revealed that she had pulmonary tuberculosis 30 years ago and received antituberculosis therapy for nine months. The laboratory results on admission were as follows: blood urea nitrogen 90 mg/dl, serum creatinine 9 mg/dl, sodium 116 mEq/L, potassium 6.6 mEq/L, albumine 2.9 g/dl, hemoglobin, 8.4 g/dl, white blood cell count 10.800/mm3, C-reactive protein 187 mg/L and erythrocyte sedimentation rate 110 mm/hour. Urinalysis showed 8.1 g/L protein, 10-12 leukocytes, 1-2 erythrocytes, while 24-hours urinalysis yielded proteinuria with 8 ml/minutes creatinine clearance value. Urine and blood cultures of the patient revealed neither bacteria or mycobacteria. PPD skin test was negative. Acid-resistant bacilli (ARB) were not detected in sequential urine samples obtained on three consecutive days. Since sputum samples could not be obtained, diagnostic procedures for sputum were not performed. Abdomen ultrasonography yielded bilateral edema and grade II echogenity in kidneys. Computed tomography of the chest showed bilateral pulmonary nodules, chronic sequela lesions, pleural scarring and calcifications, as well as minimal interstitial infiltrate. Transthoracic lung biopsy showed chronic inflammation and fibrosis, while amyloid was negative. Renal biopsy showed GTN with central caseified necrosis and granulomas, multinuclear giant cells, tubular atrophy and interstitial fibrosis. Amyloid was negative and ARB were not detected in renal biopsy sample. Definitive diagnosis was achieved by the demonstration of Mycobacterium tuberculosis nucleic acid in kidney biopsy by polymerase chain reaction (PCR). Antituberculosis therapy was not initiated since there were no signs of active tuberculosis. The patient became clinically stable following dialysis and was discharged, however, she has been undergoing hemodialysis three times a week. The aim of this case presentation was to emphasize that renal tuberculosis should be considered in the differential diagnosis of patients with end stage renal failure, especially in countries like Turkey where tuberculosis incidence is high.
2011Usefulness of various inflammatory markers to differentiate pulmonary edema from pneumonia.Isr Med Assoc JCommunity-acquired pneumonia requiring hospitalization is a severe illness with high mortality, especially if the appropriate treatment is delayed. Sometimes diagnosis is difficult due to an equivocal clinical picture or chest film, or to accompanying diseases that mask or simulate pneumonia.To assess the usefulness of certain inflammatory markers in differentiating pulmonary edema from pneumonia throughout the hospital stay in patients admitted for pneumonia or pulmonary edema of non-infectious origin and to monitor the response to treatment.The study group comprised 50 patients admitted for pneumonia, 50 admitted for pulmonary edema and 30 healthy individuals. Blood samples for determination of leukocyte count, erythrocyte sedimentation rate (ESR), fibrinogen, C-reactive protein (CRP), albumin, sCD14 and oxidized fibrinogen were drawn upon admission, at 48 and 72 hours after admission, and at discharge from the intensive care unit.The levels of sCD14 were similar in both patient groups but higher than control levels during the first 48 hours (P< 0.03). They decreased gradually with hospital stay. The concentration of oxidized fibrinogen was similar in both patient groups and significantly lower than that of the healthy control group throughout the hospitalization period.Oxidized fibrinogen and sCD14 are not reliable markers for the diagnosis of pneumonia, for its differential diagnosis from pulmonary edema, and for patient follow-up throughout hospitalization. The finding of elevated levels of oxidized fibrinogen in the group of healthy controls warrants further study to identify the factors responsible for altering fibrinogen oxidation. The other markers are more indicative.
2011Binge alcohol exposure modulates rodent expression of biomarkers of the immunoinflammatory response to orthopaedic trauma.J Bone Joint Surg AmAlcohol is a known modulator of the immune system and host-defense response. Alcohol abuse is common in trauma patients, although the influence of alcohol intoxication on the inflammatory response following major orthopaedic injury remains unknown. The aim of this investigation was to examine the influence of binge alcohol exposure on biomarkers of the systemic inflammatory response following bilateral traumatic femoral fracture in a rodent model.Ninety-two Sprague-Dawley rats were administered intraperitoneal injections of either saline solution or alcohol for three days. These animals then underwent a sham procedure or bilateral femoral intramedullary pinning and mid-diaphyseal closed fracture via blunt guillotine. The animals were killed at specific time points after the injury. Serum and lung tissue were collected, and twenty-five inflammatory markers were analyzed by immunoassay. Histological sections of lung tissue were evaluated by a board-certified pathologist.Bilateral femoral fracture significantly (p < 0.05) increased multiple serum biomarkers of inflammation. Binge alcohol treatment prior to injury significantly suppressed the increase in serum levels of interleukin (IL)-6, white blood cells, IL-2, IL-10, and C-reactive protein after the fracture. However, alcohol-treated animals were found to have increased pulmonary levels of IL-6, IL-1β, IL-2, and macrophage inflammatory protein-1α following bilateral femoral fracture. In addition, lung tissue harvested following alcohol treatment and injury demonstrated increased pathologic changes, including parenchymal, alveolar, and peribronchial leukocyte infiltration and significantly elevated pulmonary wet-to-dry ratio, indicative of pulmonary edema.Our results indicate that acute alcohol intake prior to bilateral femoral fracture with fixation in rats modulates the inflammatory response after injury in a tissue-dependent manner. Although serum biomarkers of inflammation were suppressed in alcohol-treated animals following injury, several measures of pulmonary inflammation including cytokine levels, histological changes, and findings of pulmonary edema were significantly increased following fracture with the presence of alcohol.
2012Role of matrix metalloproteinase-3 (MMP-3) and magnetic resonance imaging of sacroiliitis in assessing disease activity in ankylosing spondylitis.Rheumatol IntThe objective of this study is to evaluate the role of MMP-3 and MRI in assessing disease activity in sacroiliac joints of AS patients in comparison to the conventional measures Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Serum MMP-3 was measured in 30 patients who fulfilled the modified New York criteria for AS and in ten healthy volunteers. AS patients were categorized into those having high or low MMP-3 according to a cut-off value = 7.1 ng/ml. MRI of the sacroiliac joints (SIJs) was performed on all patients. SIJs were evaluated for enhancement and subchondral bone marrow edema. Results of MMP-3 and findings on MRI were correlated with multiple clinical parameters including BASDAI, ESR and CRP. Serum MMP-3 was significantly elevated in AS patients with active disease. Elevated MMP-3 levels were significantly associated with high BASDAI (P = 0.046), but not with ESR or CRP. MRI showed bone marrow edema and enhancement of SIJs in 19/30 patients with one patient showing enhancement only. These MRI findings were not correlated with MMP-3, BASDAI, CRP or ESR. In conclusion, serum MMP-3 is an objective measure reflecting clinical disease activity in AS. Bone marrow edema and enhancement detected by MRI of SIJs is another objective measure of disease activity, but are not correlated with MMP-3 or the conventional parameters as BASDAI, ESR, or CRP. Although both MMP-3 and MRI can reflect disease activity in AS they seem to be unrelated, perhaps each is reflecting a different aspect of disease activity. MMP-3 and MRI should be considered together with BASDAI in assessing disease activity and in guiding the available recommendations for initiation of biologics in AS.
2011A case of femoral hemorrhage in a patient with microscopic polyangiitis with low levels of myeloperoxidase-antineutrophil cytoplasmic autoantibody.Clin Exp NephrolWe present the case of a 67-year-old female with femoral hemorrhage accompanied by microscopic polyangiitis. She was admitted to our hospital with symptoms of general fatigue, fever, and edema of the lower limbs. She was diagnosed with microscopic polyangiitis on the basis of the cardinal symptoms of the condition, including rapidly progressive glomerulonephritis and the presence of myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA), albeit at a low titer. Renal biopsy demonstrated the presence of fibrocellular crescent-shaped glomeruli with interstitial infiltration. No immune deposits were detected in immunofluorescence studies. The patient was treated with steroids and anti-platelet agents; subsequently, the inflammatory reaction subsided and MPO-ANCA and C-reactive protein titers decreased. However, on day 14, the patient experienced sudden onset of swelling in the left femoral region accompanied by hypotension. Her hemoglobin level dropped from 8.8 to 4.5 g/dl in the subsequent hours. Although computed tomography of the legs revealed an extensive hematoma in the left quadriceps femoris muscle, the patient recovered after receiving a transfusion and supportive therapy with discontinuation of dipyridamole. Thereafter, her renal function improved, and she was discharged. To our knowledge, this is the first report of a case of microscopic polyangiitis accompanied by femoral hemorrhage.
2010[Evaluation of MRI in the diagnosis of rheumatoid arthritis].Zhonghua Yi Xue Za Zhito study the features of rheumatoid arthritis (RA) on MRI of hands and wrists and compare MRI with clinical manifestations and laboratory tests of RA.a total of 25 patients fulfilling the 2009 ACR/EULAR RA criteria were enrolled. MRI and plain films of hands and wrists and clinical data of swollen joints, tender joints, visual scale (VAS) score, DAS28 score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), RF classification, anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) were obtained simultaneously.MRI revealed pathologic findings on the wrist and hand joints in all diagnosed RA patients. VAS had a positive correlation with bone marrow edema(r = 0.562, P = 0.003). Although the disease duration was less or more than 1 year, the difference of bone erosion had statistical significance between anti-CCP antibody-positive group and anti-CCP antibody negative group (all P = 0.000). The serum concentration of RF-IgA had a positive correlation with bone marrow edema (r = 0.561, P = 0.041). The synovitis score of MRI of RA was higher in the RF-IgG positive group than that in the RF-IgG negative group (P = 0.035). There was significant difference in MRI synovitis between the RF-IgG or RF-IgM positive and negative groups of patients with a disease course of under 1 year (P = 0.015, P = 0.007). The serum CRP level had a positive correlation with arthroderma (r = 0.457, P = 0.022).MRI is proved to be a valuable examination for an early diagnosis and assessment of RA.
2010How many general and inflammatory variables need to be fulfilled when defining sepsis due to the 2003 SCCM/ESICM/ACCP/ATS/SIS definitions in critically ill surgical patients: a retrospective observational study.BMC AnesthesiolIt has never been specified how many of the extended general and inflammatory variables of the 2003 SCCM/ESICM/ACCP/ATS/SIS consensus sepsis definitions are mandatory to define sepsis.To find out how many of these variables are needed to identify almost all patients with septic shock.Retrospective observational single-centre study in postoperative/posttraumatic patients admitted to an University adult ICU. The survey looked at 1355 admissions, from 01/2007 to 12/2008, that were monitored daily computer-assisted for the eight general and inflammatory variables temperature, heart rate, respiratory rate, significant edema, positive fluid balance, hyperglycemia, white blood cell count and C-reactive protein. A total of 507 patients with infections were classified based on the first day with the highest diagnostic category of sepsis during their stay using a cut-off of 1/8 variables compared with the corresponding classification based on a cut-off of 2, 3, 4, 5, 6, 7 or 8/8 variables.Applying cut-offs of 1/8 up to 8/8 variables resulted in a decreased detection rate of cases with septic shock, i.e., from 106, 105, 103, 93, 65, 21, 3 to 0. The mortality rate increased up to a cut-off of 6/8 variables, i.e., 31% (33/106), 31% (33/105), 31% (32/103), 32% (30/93), 38% (25/65), 43% (9/21), 33% (1/3) and 0% (0/0).Frequencies and mortality rates of diagnostic categories of sepsis differ depending on the cut-off for general and inflammatory variables. A cut-off of 3/8 variables is needed to identify almost all patients with septic shock who may benefit from optimal treatment.
2010[Preliminary investigation of the changes and mechanism of Leptin after myocardial ischemia/reperfusion injury].Zhongguo Wei Zhong Bing Ji Jiu Yi XueTo explore the effect of rat myocardial ischemia/reperfusion (I/R) injury on serum Leptin, endothelin (ET), C-reactive protein (CRP) and myocardial Leptin expression, and discuss the role of Leptin in myocardial I/R injury.Fifty Sprague-Dawley (SD) rats were randomly divided into sham-operation, ischemia and I/R 1, 2, 3 hours groups, with 10 rats in each group. Anterior descending artery of the left coronary artery was ligated for 45 minutes and released for 1, 2 and 3 hours to establish myocardial I/R model, and the said artery of the rats in sham-operation group was not ligated. Blood from left femoral artery was collected at different time points, and serum Leptin, ET and CRP contents were detected. Myocardial tissue was harvested, and stained with hematoxylin-eosin (HE) and immunohistochemistry for its observation of the myocardial pathological changes and Leptin protein expression.Serum Leptin content (μg/L) of ischemia group was significantly lower than that of sham-operation group (4.69±1.67 vs. 6.48±2.02, P<0.05); as the reperfusion time was prolonged, serum Leptin level increased gradually, and the level of I/R 3-hour group recovered to that before injury [(6.59±2.58) μg/L]. ET content (ng/L) of ischemia group was significantly higher than that of sham-operation group (110.58±37.86 vs. 80.74±34.43, P<0.05), the levels of ET in I/R 1, 2 and 3 hours groups were significantly lower than those of ischemia group (35.87±13.56, 31.98±10.88, 34.56±14.37 vs. 110.58±37.86, all P<0.05). CRP content (mg/L) of ischemia group was significantly higher than that of sham-operation group (13.12±4.82 vs. 3.24±1.72, P<0.01); as the reperfusion time was prolonged, serum CRP level increased gradually, and the levels of I/R 1, 2 and 3 hours groups were significantly higher than those of ischemia group (18.37±6.48, 24.30±9.51, 27.08±8.32 vs. 13.12±4.82, all P<0.05). Pathological examination showed that there was necrosis of ischemic myocardial cells in ischemia group, with mild congestion and edema in interstitial spaces. After I/R injury, the myocardial cells showed coagulative necrosis, and there was severe congestion of myocardial interstitial. Immunohistochemistry results showed that there was a tendency of decrease in Leptin protein expression in the early phase but increase in the late phase after the injury.Leptin content in the serum and myocardial tissue decreases significantly in the early phase after myocardial I/R but increases gradually in the rehabilitative phase, suggesting that Leptin maybe a stress protective factor against I/R-induced myocardial injury. There is a possible association between Leptin and the early increase followed by a delayed decrease of ET as well as the increase of CRP.
2010Para-aortic Lymphadenopathy Associated with Kawasaki Disease.Iran J PediatrKawasaki disease is an acute vasculitis that occurs mainly in children. Cervical lymphadenopathy is one of the major presenting manifestations of Kawasaki disease. We report a case of Kawasaki disease with para aortic lymphadenopathy, as an unusual feature in this disease.This 2.5 year old girl presented with persistent high grade fever, erythematous rash, bilateral non purulent conjunctivitis, red lips, and edema of extremities. Laboratory results included an elevated erythrocyte sedimentation rate, leukocytosis, anemia, and positive C-reactive protein. On second day after admission she developed abdominal pain. Ultrasonography of abdomen revealed multiple lymph nodes around para aortic area, the largest measuring 12mm×6mm. Treatment consisted of aspirin and high dose intravenous γ-globulin. Ultrasonography and CT scan of abdomen performed one week later showed disappearance of the lymph nodes.There are few previous reports of lymphadenopathy in unusual sites such as mediastinum in Kawasaki disease. Para aortic lymph nodes enlargement might be an associated finding with acute phase of Kawasaki disease. In these patients a close observation and ultrasonographic follow up will prevent unnecessary further investigation.
2011[Cerebral actinomycosis pseudotumor: a case report].Rev Neurol (Paris)Cerebral actinomycosis is rare and difficult to diagnose.We report a case of a 45-year-old man hospitalized for seizures associated with fever and left hemiparesis. The white cell count and C-reactive protein were elevated. HIV serology was negative. Blood cultures remained sterile. The CT scan revealed hyperdense nodular lesions in the occipital area, with annular contrast uptake and peripheral edema causing a mass effect, suggestive of brain metastasis. The pathology examination of a surgical specimen disclosed cerebral actinomycosis. A dental origin of the infection was suspected. Hemiparesis remained after a 12-month antibiotic regimen associated with dental care and short-term corticosteroid therapy.Actinomycosis should be discussed as a possible diagnosis for all cerebral lesions, particularly in patients with a potential dental infection. Histology is required for positive diagnosis. Antibiotic therapy alone is generally sufficient; surgery is often performed for diagnostic purposes.
2010Miniaturized biocompatible cardiopulmonary bypass for the Fontan procedure.Surg TodayPostoperative inflammatory response and perioperative systemic edema are the risks of failed Fontan circulation. We evaluated the efficiency of the miniaturized, poly-2-methoxyethylacrylate (PMEA)-coated cardiopulmonary bypass (CPB) circuit, which we devised in 2003, in the Fontan circulation.Thirty-seven patients who underwent the Fontan procedure between March 1996 and December 2006 were divided into two groups: one consisting of patients with a priming-volume >250 m on uncoated conventional bypass (group C; n = 20), and one consisting of those with miniaturized (<200 ml) and PMEA-coated circuits (group M; n = 17). We compared the body weight gain (%BWG), minimum platelet count, maximum postoperative C-reactive protein (CRP), and minimum hematocrit (Hct) levels during the operation, maximum white blood cell (WBC) count, and postoperative pleural effusion, between the two groups. Stepwise multiple logistic regression analyses were used to investigate the most affecting factors.The %BWG and CRP levels were significantly lower in group M (P = 0.047 and P = 0.012, respectively). The minimum platelet count was significantly higher in group M (P = 0.012). There were no significant differences in postoperative pleural effusion, minimum Hct, or maximum WBC.The miniaturized biocompatible CPB system reduced perioperative inflammatory responses.
2010[Arthritis of the atlanto-axial joint with inflammatory neck pain as a primary manifestation of seronegative rheumatoid arthritis].Dtsch Med WochenschrA 68-year-old woman with known degenerative joint disease suffered from increasing neck pain. Physical examination revealed painfully restricted movement of the cervical spine.Erythrocyte sedimentation rate and C-reactive protein were increased. Tests for rheumatoid factors, antinuclear, anti-citrullinated protein and anti-neutrophil cytoplasmic antibody were negative. Cervical spine x-ray showed osteochondrosis with partially bridging spondylosis at C5/C6, but there was no atlanto-axial dislocation. Magnetic resonance imaging (MRI) revealed bone marrow edema and hyperintensity of the odontoid process, but there were no indications of fissures or fracture lines.These findings indicated seronegative rheumatoid arthritis, with predominantly active atlanto-axial arthritis. After methotrexate and prednisolone had been administered the symptoms improved rapidly and inflammatory parameters returned to normal. Three months later no atlanto-axial arthritis was seen at MRI.Rheumatoid arthritis involving the atlanto-axial region should be considered in patients with persisting neck pain and signs of inflammation.
2011Non-surgical periodontal therapy improves serum levels of C-reactive protein and edematous states in female patients with idiopathic edema.J PeriodontolThe relationship between periodontal disease and systemic disease is revealing new and exciting associations. Idiopathic edema presents a clinical syndrome with obscure pathophysiology. The present study investigates whether non-surgical periodontal therapy is beneficial in patients who are not responding to conventional treatment of idiopathic edema.Thirty patients with idiopathic edema were allocated to intervention and control groups. All the subjects were assessed for systemic (body weight, body mass index, visual scale of edema, serum C-reactive protein, and serum albumin) and periodontal (plaque index, calculus index, and gingival index) parameters. Non-surgical periodontal therapy, including oral hygiene instructions, scaling and root planing, and systemic antibiotic therapy, was provided in the intervention group. Both groups were reevaluated after 4 weeks.Both groups were comparable at baseline. All parameters, except serum albumin, showed significant improvement after periodontal therapy. The control group showed further worsening of these parameters.This study shows that sources for systemic inflammation, such as periodontal disease, could affect the pathogenesis of idiopathic edema. Successful elimination of such covert sources of inflammation leads to a clinical benefit in patients who are distressed by this condition.
2010Pure intracerebral mass lesion of adult T-cell leukemia/lymphoma--case report.Neurol Med Chir (Tokyo)A 48-year-old female presented with a rare case of adult T-cell leukemia/lymphoma (ATL) occurring as only intracerebral mass lesion manifesting as progressively worsening headaches, transient mild weakness of the left lower extremity, bilateral papilledema, and left homonymous hemianopsia. Laboratory examination showed transient leukocytosis (15900/microl) without febrile episode or elevation of C-reactive protein. Neuroimaging revealed a solitary enhanced mass lesion in the right occipital lobe adjacent to the choroid plexus with prominent perifocal edema. The patient underwent gross total removal, and the histological diagnosis was intracerebral ATL. She underwent radiation therapy and chemotherapy after local recurrence and metastasis to an optic nerve. The lesions had disappeared on magnetic resonance imaging with contrast medium 10 months after onset and no recurrence was detected even 5 years later. Intracerebral ATL should be considered in the differential diagnosis of intracerebral mass without leukemia or systemic lymphoma.
2010Chronic hip pain in a boy with mental retardation and cerebral palsy.J Dev Behav PediatrJonny is a 13 year old boy with spastic quadriparesis and severe mental retardation following Haemophilus influenza type B (HIB) meningitis at 2-months of age. Signs of meningitis started on the evening of his 2-month immunizations that included the HIB vaccine. He presented to his pediatrician with left hip pain that occurred intermittently for a few years and more frequently in the past six months. His parents initially attributed the pain to whizzing around the back yard in a motorized wheelchair. An earlier evaluation of hip pain led to bilateral femoral osteotomies for hip dysplasia. Obesity, associated with inactivity and a tendency to consume fatty foods, complicates Jonny's disabilities. His only activity is a modest amount of physical therapy at school and "floor time" for about one hour each day at home. In the office of his pediatrician, Jonny is friendly, smiling, and verbalizing a few words with his limited expressive vocabulary. He is resistant to a hip examination and grimaces with manipulation of his left hip. Spasticity of the left leg appears increased compared to previous examinations. He has nonpitting edema of his lower legs and feet, a cryptorchid left testicle, and a somewhat tender left inguinal area. Jonny lives with his mother and father in a small house on a busy street less than one-half mile from the pediatrician's office. Jonny's pediatrician often sees him in his wheelchair, accompanied by his mother or grandmother, and waves or stops to chat. He has van services to school, and there is a Hoyer lift in the home, but his parents do not own a van. Recently, Jonny's father finds it more difficult to lift him. The family has also been challenged by the mental health problems of Jonny's two older brothers, and a serious eye injury suffered by his middle brother in a motor-vehicle accident. Jonny's pediatrician has cared for him and his two brothers since birth. Although the parents continue to believe that the HIB vaccine caused his catastrophic illness, they remain with the pediatrician. In general, they are satisfied with the individualized educational plan at a local public school. When he was 6.5 years old, Jonny's school aid reported that he attempted to touch her in the genital area. The pediatrician attended the meeting to review this incident and successfully advocated for Jonny by pointing out that this was an isolated incident; it did not occur again. At 6 years old Jonny functioned in the 1.5-2.5 year old range with motor skills in the 6-12 month level according to the Bayley Scales of Infant Development and the Vineland Adaptive Behavior Scales. In the past a neurologist and a physiatrist saw Jonny, but both of these individuals moved from the community. He had prior evaluations at a children's orthopedic clinic at a small community hospital and at the local Shriner's hospital. He had a tonsillectomy and adenoidectomy at 7 years old. He is currently treated for constipation and receives dental care at a clinic for people with disabilities. His pediatrician has always respected the parents for their care and obvious love for their disabled child. However, parental resistance to addressing major issues such as obesity has frustrated his pediatrician. When the pediatrician suggested that Jonny was eligible for the state's managed care program, which would convert Medicaid coverage to a state sponsored program with more extensive services and case management, Jonny's mother repeatedly said that she would "think it over." At the current visit, the pediatrician recommended an adjustment of Jonny's wheelchair, a hip x-ray, a referral to Shriner's Hospital, and an appointment with a pediatric surgeon to address the undescended testicle and possible hernia. Jonny's mother mentioned that he had been to Shriner's Hospital for hip pain two years earlier but was told nothing could be done "because nothing was wrong with his bone." The hip x-ray was normal as well as a complete blood count and a C-reactive protein. The pediatric surgeon did not find a hernia and deferred treatment of the cryptorchid testicle. His parents contacted the wheelchair company to arrange adjustments. The pediatrician called the medical director at the Shriner's Hospital to discuss Jonny's case, but 2 months after the initial visit, the parents had not arranged for an appointment at the Shriner's Hospital. Jonny's hip pain persisted. The pediatrician now wonders how he can more effectively address Jonny's current problems and improve overall care for him and his family.
2010[Clinical analysis of 75 patients with severe influenza A H1N1 in Qinghai Province].Zhongguo Wei Zhong Bing Ji Jiu Yi XueTo observe clinical features of severe influenza A H1N1 in Qinghai Province.The clinical data of 75 severe influenza A H1N1 patients were analyzed retrospectively in regard to common features, clinical symptoms, signs, laboratory data and treatments hospitalized in Qinghai Hospital for Infectious Diseases during September 4, 2009 to December 31, 2009.The first case with severe influenza A H1N1 was diagnosed on October 14, and up to 75 patients (47.78%) on December 31. Among 75 patients, 45 patients were from rural areas (60.00%) and 30 patients were urbanites, 48 patients were male, and 27 female. Fifty-three patients were complicated with pneumonia (70.67%) and 41 patients with pre-existing medical conditions (54.67%), 65 patients with fever (86.67%), 63 patients with cough and sputum (84.00%), 61 patients with dyspnea (81.33%), 1 patients with meningitis as the main manifestation, 2 patients with acute pulmonary edema and left heart failure, 28 patients with leucopenia (37.33%), 28 patients with myocardial enzyme abnormalities (37.33%), 23 patients with blood glucose abnormalities (30.67%), 8 patients with coagulopathy (10.67%), 4 patients with lipid abnormalities (5.33%), 51 patients with increased C-reactive protein (68.00%). Forty-eight patients received oseltamivir, 27 patients received anti-virus "Jun Ke Ao Wei" capsules. Low molecular weight heparin was given to 27 patients for anticoagulation, and 22 were treated with methylprednisolone. In 33 patients who underwent non-invasive mechanical ventilation, among them it was switched to invasive mechanical ventilation in 10 patients. Second-line antibiotics were used, and sputum culture was done. In 8 patients with fungal infection anti-fungal therapy was given. Except 1 patient out of 75 patients died, and the rest were cured.In Qinghai Province, cases with influenza A H1N1 peaked early with relative high incidence of severe cases. Patients suffering from influenza A H1N1 are susceptible to pulmonary complications. The condition of patients rapidly deteriorate, and they are prone to develop respiratory failure, disseminated intravascular coagulation and multiple organ failure.
2010Case of remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome) showing dermatomyositis-like eruption.J DermatolA 73-year-old woman developed linear erythema at the sites of scratching-induced scars on the bilateral thighs 2 weeks before the initial consultation. Subsequently, edematous erythema developed in the upper eyelids, dorsum of the nose and the face, and pitting edema in the dorsum of the bilateral hands and feet. The C-reactive protein (CRP) level was 8.2 mg/dL and erythrocyte sedimentation rate (ESR) 121 mm/h. The antinuclear antibody titer was 1:160, and rheumatoid factor (RF) and anti-Jo-1 antibody were negative. X-ray examination of the bilateral hands showed neither narrowing of the joint spaces nor bone erosion. Ga scintigraphy showed synovitis of the bilateral wrists. A diagnosis of remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE) was made. The erythema disappeared after diclofenac sodium administration. However, because the joint swelling and pitting edema did not improve, p.o. administration of prednisolone (20 mg/day) was initiated. The CRP and ESR levels normalized 2 months after the initiation of administration, and pitting edema disappeared after 3 months. We report this case because linear erythema like that observed in dermatomyositis has not been described as eruptions associated with RS3PE.
2010Anti-inflammatory and antioxidant effects of Jeevaneeya Rasayana: an ayurvedic polyherbal formulation on acute and chronic models of inflammation.Immunopharmacol ImmunotoxicolThe present study was aimed to establish the efficacy of Jeevaneeya Rasayana (JR), an ayurvedic polyherbal formulation, in adjuvant-induced arthritic (AIA) rat model with reference to mediators of inflammation. The methanolic (MJR), ethanolic (EJR), and water extracts (WJR) of JR were prepared and their anti-inflammatory activity in carrageenan-induced acute model was evaluated. MJR at a dose of 25 mg/kg showed significantly higher anti-inflammatory effect than EJR, WJR, and standard drug diclofenac. MJR also significantly decreased the paw edema in AIA rats. Activities of cyclooxygenase, 5-lipoxygenase, and myeloperoxidase were decreased significantly on treatment with MJR. Supplementation with MJR increases the activities of antioxidant enzymes and the level of glutathione content. The increment in the concentration of C-reactive protein, thiobarbituric acid reactive substance, and ceruloplasmin observed in arthritic rats were found to be significantly restored in MJR treated rats. Thus, the results demonstrated the potential beneficiary effect of methanolic extract of Jeevaneeya Rasayana on acute and chronic models of inflammation.
2010Bone marrow edema is the most specific finding for rheumatoid arthritis (RA) on noncontrast magnetic resonance imaging of the hands and wrists: a comparison of patients with RA and healthy controls.J RheumatolTo evaluate the sensitivity and specificity of magnetic resonance imaging (MRI) in detecting erosions, bone edema, and synovitis in the metacarpophalangeal and wrist joints for rheumatoid arthritis (RA).MRI scans of bilateral hands and wrists of 40 healthy subjects and 40 RA patients were performed using 0.2 T extremity-MRI and read blindly using a modified RA MRI (RAMRIS) system (no contrast injection, imaging in 1 plane only). To determine interreader reliability, images of 10 randomly selected subjects were read independently by a musculoskeletal radiologist.A total of 3360 bones were evaluated. Patients with RA had significantly more erosions as well as higher scores for bone edema and synovitis than healthy subjects. Age had a significant effect on the number of erosions in both groups. However, when disease duration was factored in, age became insignificant in RA patients. Erosion number correlated with positive rheumatoid factor and higher C-reactive protein values. The intraclass correlation coefficient between the 2 readers was 0.76 for individual joints and 0.88 for total scores. When having a single erosion was used as a positive test for RA, the sensitivity of this test was 90%, but the specificity was only 35%. Presence of bone edema provided 65% sensitivity and 82.5% specificity. Eliminating the lunate from scoring for bone edema increased the specificity to 87.5% while decreasing the sensitivity to 62.5%.While MRI is a highly sensitive tool for identifying and tracking the progression of erosions, erosions detected by MRI with measures commonly used in a rheumatologist's office (no contrast, imaging in 1 plane) provide low specificity for RA. Bone marrow edema is the most specific MRI lesion for RA in this setting.
2009Clinical, radiological, and biochemical characteristics in patients with diseases mimicking polymyalgia rheumatica.Clin Interv AgingTo find out clues to differentiate between polymyalgia rheumatica (PMR) and other diseases that mimic PMR. We studied Japanese patients with PMR (n = 7), pseudogout (n = 1), remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome (n = 1), and post-infectious polyarthritis (n = 1). The distribution of inflammation in patients was evaluated using a gallium-67 scintigraphy. We measured serum C-reactive protein (CRP), matrix metalloproteinase-3 (MMP-3), and vascular endothelial growth factor (VEGF) in patients before and after treatment. Further, we compared the clinical course of PMR with that of other diseases that mimic PMR. Patients with pseudogout, RS3PE syndrome, post-infectious polyarthritis manifested similar changes in scintigraphic findings and serum CRP, MMP-3, and VEGF levels to PMR before the treatment. A significant reduction in serum CRP levels at one week after use of nonsteroidal anti-inflammatory drugs (NSAIDs) is a good clue to differentiate pseudogout and post-infectious polyarthritis from PMR. Chondrocalcinosis in the radiographs of joints is also effective to differentiate pseudogout from PMR. A small reduction of CRP levels after NSAIDs use and promptly ameliorated CRP and symptoms by a low-dose steroid therapy, which was commonly observed in patients with PMR, were also found in a patient with RS3PE syndrome. Pitting edema of the back of hands and gallium uptake in metacarpophalangeal (MCP) joints were useful to differentiate RS3PE syndrome from PMR. In conclusion, pseudogout, RS3PE syndrome, post-infectious polyarthritis should be included in the spectrum of diseases mimicking PMR. A promptly decreased serum CRP level by NSAIDs is a good clue to differentiate pseudogout and post-infectious polyarthritis from PMR. Pitting edema of the back of hands and symmetric gallium uptake in MCP joints are characteristic for RS3PE syndrome.
2010Angioedema: 6 years experience with fourteen cases.Auris Nasus LarynxTo study the difference in the findings between the causes of angioedema and the characteristics of angioedema induced by angiotensin receptor II blockers (ARBs), and to investigate whether laboratory examinations for acute phase inflammatory markers can aid in diagnosis and predict airway risk.We retrospectively reviewed fourteen cases of patients with angioedema that were treated from 2000 to 2006. Data were collected regarding age, sex, location of the edema, cause, time course of resolution and laboratory examinations (leukocyte counts, serum C-reactive protein (CRP) level, complement function and the activity of C1 esterase inhibitor).The causes of angioedema were ACEIs in six patients (42.9%), candesartan (ARB) in three (21.4%), HAE (types 1 and 2) in two, and unknown in three. Of these patients, 71.4% exhibited edema in the floor of the mouth, irrespective of the cause. Two patients with edema induced by candesartan exhibited both lingual and laryngeal edemas. The remaining one with candesartan-induced edema exhibited edema in the neck and mediastinum and pleural effusion. The average time to resolution was 4.1 days, ranging from one to twelve days. The edema in eleven patients resolved with conservative therapy, while three patients underwent tracheotomy. In two patients with candesartan-induced edema, although the edemas resolved completely after cessation of candesartan administration, the edemas reappeared in the same locations, two and thirty days after the cessation of candesartan for each patient. None of the patients with angioedema induced by ACEIs exhibited elevation of serum CRP levels. No significant differences were found for leukocyte counts and serum CRP levels between patients with angioedemas induced by ACEIs, ARB and those of unknown cause. No significant differences were observed in the above findings between the patients who underwent tracheotomy and those who did not. Two patients exhibited low C4 levels, and one of the two exhibited no activity of C1 esterase inhibitor.Consistent with previous reports, angioedema in the floor of the mouth extending to the tongue should be considered as a possible risk factor for airway compromise. Laboratory examinations for acute phase inflammatory markers are not useful for diagnosis and are not predictive for airway intubation and tracheotomy. Angioedema induced by candesartan can present in anomalous sites and reappear following drug cessation even if the edema has resolved completely.
2009Can magnetic resonance imaging differentiate undifferentiated arthritis based on knee imaging?J RheumatolTo compare findings as observed on enhanced magnetic resonance imaging (MRI) of the knee joints, in oligoarticular-undifferentiated arthritis (UA) in those with established rheumatoid arthritis (RA) and spondyloarthropathy (SpA).A total of 55 patients with knee arthritis were consecutively recruited for the study, including 25 with undifferentiated oligoarthritis of the knee joint(s), 15 fulfilling the American College of Rheumatology criteria for RA and 15 with SpA. Laboratory investigations included erythrocyte sedimentation rate, C-reactive protein, complete blood count, aspartate aminotransferase, alanine aminotransferase, serum creatinine, and urine analysis. In all patients in the UA and in the RA group, rheumatoid factor and anti-CCP2 antibody (ELISA) were tested. All patients underwent enhanced MRI of the more symptomatic knee. All groups were compared in terms of demographics, laboratory investigations, and MRI findings.Synovial thickness differed significantly in the RA group compared to UA and SpA groups (p < 0.001). The RA group showed a higher rate of bony and cartilaginous erosions and bone marrow edema compared to UA and SpA groups (p < 0.001). Enthesitis was found in all patients in the SpA group (100%) and differed from RA and UA groups (p < 0.001).Patients with RA showed more destructive changes in terms of synovial thickening, bone marrow edema, cartilaginous and bone erosions compared to UA and SpA groups. Enthesitis is a common feature on MRI in SpA, while absent in the RA and UA groups. This latter finding may have important clinical implications for classification purposes, and can help to determine the evolving pattern of patients with UA of the knee joint.
2009Tako-tsubo cardiomyopathy observed in a patient with sepsis and transient hyperthyroidism.Monaldi Arch Chest DisA 55-years-old woman, with a history of hypertension and ischemic stroke with residual left hemiparesis, was admitted to our hospital because of dyspnoea with clinical evidence of acute pulmonary edema. She was found to have a sinus tachycardia with ST-elevation in leads D1, aVL and V1-V4 in the electrocardiogram, and akinesis of the left ventricular apex with overall left ventricular systolic function being severely impaired and an ejection fraction of 28% on echocardiography. Orotracheal intubation was performed and mechanical ventilation was immediately started. Emergency cardiac catheterization was performed 2 h after the symptom onset. Coronary angiography showed no significant coronary artery disease. Blood analysis revealed an increase in the creatine kinase MB fraction, a significant positive detection in troponin T, a white blood cell count of 35000 per microliter, C-reactive protein of 59,9 mg/dl, and transient elevation in the concentration of free triiodothyronine, free thyroxine, thyroid globulin antibody, and thyroid peroxidase antibody. The symptoms improved during the next days, and follow-up echocardiography 18 days later showed complete resolution of the left ventricular dysfunction. These data suggest that tako-tsubo cardiomyopathy may be induced in patients with sepsis and transient hyperthyroidism.
2009Mural inflammation in Crohn disease: location-matched histologic validation of MR imaging features.RadiologyTo validate proposed magnetic resonance (MR) imaging features of Crohn disease activity against a histopathologic reference.Ethical permission was given by the University College London hospital ethics committee, and informed written consent was obtained from all participants. Preoperative MR imaging was performed in 18 consecutive patients with Crohn disease undergoing elective small-bowel resection. The Harvey-Bradshaw index, the C-reactive protein level, and disease chronicity were recorded. The resected bowel was retrospectively identified at preoperative MR imaging, and wall thickness, mural and lymph node/cerebrospinal fluid (CSF) signal intensity ratios on T2-weighted fat-saturated images, gadolinium-based contrast material uptake, enhancement pattern, and mesenteric signal intensity on T2-weighted fat-saturated images were recorded. Precise histologic matching was achieved by imaging the ex vivo surgical specimens. Histopathologic grading of acute inflammation with the acute inflammatory score (AIS) (on the basis of mucosal ulceration, edema, and quantity and depth of neutrophilic infiltration) and the degree of fibrostenosis was performed at each site, and results were compared with MR imaging features. Data were analyzed by using linear regression with robust standard errors of the estimate.AIS was positively correlated with mural thickness and mural/CSF signal intensity ratio on T2-weighted fat-saturated images (P < .001 and P = .003, respectively) but not with mural enhancement at 30 and 70 seconds (P = .50 and P = .73, respectively). AIS was higher with layered mural enhancement (P < .001), a pattern also commonly associated with coexisting fibrostenosis (75%). Mural/CSF signal intensity ratio on T2-weighted fat-saturated images was higher in histologically edematous bowel than in nonedematous bowel (P = .04). There was no correlation between any lymph node characteristic and AIS.Increasing mural thickness, high mural signal intensity on T2-weighted fat-saturated images, and a layered pattern of enhancement reflect histologic features of acute small-bowel inflammation in Crohn disease.
[Enteritis and cystitis - a cause of abdominal pain in lupus].Acta Reumatol PortWe present a case of a 28-year-old black female patient with a previous diagnosis of overlapping syndrome of lupus and rheumatoid arthritis, treated with corticosteroids and methotrexate, who was admitted to our department due to abdominal pain with vomits and diarrhea for 15 days. On complementary evaluation elevated C-reactive protein and erythrocyte sedimentation rate, lactate dehydrogenase and amylase levels were detected, C3 was reduced, blood, faeces, peritoneal fluid and urine cultures were negative; abdominal computerized tomography disclosed jejunal thickening with parietal edema, bilateral ureterohydronephrosis and bladder parietal thickening; on endoscopy with biopsy there was chronic pangastritis and duodenitis; cystoscopy with biopsy showed chronic cystitis. Those aspects suggested lupus enteritis and cystitis which appear rarely associated and have poor prognosis. This patient was treated with high dose corticosteroids followed by azathioprine and prednisolone, with clinical and imaging improvement.
2009High serum cartilage oligomeric matrix protein determines the subset of patients with early-stage rheumatoid arthritis with high serum C-reactive protein, matrix metalloproteinase-3, and MRI-proven bone erosion.J RheumatolTo identify the significance of serum cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in patients with early-stage rheumatoid arthritis (RA) in relation to other serologic variables and magnetic resonance imaging (MRI) features.Ninety-eight patients with early-stage RA, whose disease duration from onset was less than 2 years, were enrolled. The objective measures at baseline were Disease Activity Score (DAS28), serum C-reactive protein (CRP), serum matrix metalloproteinase-3 (MMP-3), serum antibodies against cyclic citrullinated peptide (anti-CCP), and MRI features of both wrist and finger joints. The MRI features included the number of sites scored positive for synovitis, bone edema, and bone erosion.Serum COMP concentration was not different among groups identified with low, moderate, and high DAS28-CRP values. However, COMP values were statistically high in subjects positive for bone erosions on MRI compared with the subjects who were negative for bone erosions. A positive correlation of COMP with CRP and with MMP-3 values was also identified.Elevation of COMP may reflect joint damage that is dependent on the synovial inflammatory process in early-stage RA.
2009Serial contrast-enhanced cardiac magnetic resonance imaging demonstrates regression of hyperenhancement within the coronary artery wall in patients after acute myocardial infarction.JACC Cardiovasc ImagingOur aim was to determine whether serial contrast-enhanced cardiac magnetic resonance (CE-CMR) is useful for the characterization of tissue signal changes within the coronary vessel wall in patients after acute myocardial infarction (AMI).Inflammation plays a key role in the development of AMI. CE-CMR of the vessel wall has been found useful for the characterization of inflammatory tissue signal changes in patients with carotid artery stenosis, giant cell arteritis, or Takayasu's arteritis; however, it has never been serially performed in the coronary artery wall in patients with acute and chronic myocardial infarction using a gadolinium-based contrast medium and compared with systemic markers of inflammation.CE-CMR using a T1-weighted 3-dimensional gradient echo inversion recovery sequence of the coronary artery wall and 0.2 mmol/kg of gadolinium-diethylenetriaminepentaacetic acid was performed in 10 patients with AMI 6 days and 3 months after coronary intervention and in 9 subjects without coronary artery disease on invasive coronary angiography. Contrast-to-noise ratio (CNR) within the coronary artery wall was quantified in comparison with blood signal.Patients with AMI demonstrated a significantly increased coronary vessel wall enhancement 6 days after infarction compared with normal subjects (CNR 7.8 +/- 4.4 vs. 5.3 +/- 3.2, p < 0.001). Three months after infarction, CNR decreased to 6.5 +/- 4.7 (p < 0.03). This decrease paralleled declines in C-reactive protein. Angiographically normal segments showed no contrast changes, but CNR significantly decreased in stenotic segments, from 10.9 +/- 3.8 to 6.8 +/- 5.0 (p < 0.002), resulting in a reduction of enhanced segments from 70% to 25% (p < 0.01).Serial CE-CMR identified changes in spatial extent and intensity of coronary contrast enhancement in patients after AMI. This technique may be useful for the characterization of transient coronary tissue signal changes, which may represent edema or inflammation during the post-infarction phase. In addition, CE-CMR may offer the potential for visualization of inflammatory activity in atherosclerosis associated with acute coronary syndromes.
2009Anti-inflammatory activity of flower extract of Calendula officinalis Linn. and its possible mechanism of action.Indian J Exp BiolCalendula officinalis flower extract possessed significant anti-inflammatory activity against carrageenan and dextran-induced acute paw edema. Oral administration of 250 and 500 mg/kg body weight Calendula extract produced significant inhibition (50.6 and 65.9% respectively) in paw edema of animals induced by carrageenan and 41.9 and 42.4% respectively with inflammation produced by dextran. In chronic anti-inflammatory model using formalin, administration of 250 and 500 mg/kg body weight Calendula extract produced an inhibition of 32.9 and 62.3% respectively compared to controls. TNF-alpha production by macrophage culture treated with lipopolysaccharide (LPS) was found to be significantly inhibited by Calendula extract. Moreover, increased levels of proinflammatory cytokines IL- 1beta, IL-6, TNF-alpha and IFN-gamma and acute phase protein, C- reactive protein (CRP) in mice produced by LPS injection were inhibited significantly by the extract. LPS induced cyclooxygenase-2 (Cox-2) levels in mice spleen were also found to be inhibited by extract treatment. The results showed that potent anti-inflammatory response of C. officinalis extract may be mediated by the inhibition of proinflammatory cytokines and Cox-2 and subsequent prostaglandin synthesis.
2009Fatal acute compartment syndrome in patients after surgical treatment: 2 case reports.Leg Med (Tokyo)This report describes 2 cases died from acute compartment syndrome after surgical treatment. Case 1 was a 30-year-old man suffered from upper arm fracture, who complicated with the acute compartment syndrome at the following day after surgical fixation, and died 6 days later. Case 2 was a 9-year-old woman sustained medial malleolus sprain, who experienced plaster cast immobilization and died 7 days after management. At autopsy, swollen and necrotized skeletal muscles with edema were detected in the involved region in both cases. Histopathologically, hemorrhage and infiltration of neutrophils were observed in the skeletal muscles. Intensive positive immunoreactivity of myoglobin was detected in granular casts in distal convoluted tubules by immunohistochemical staining. Marked elevation in serum urea nitrogen uric acid, creatinine and C-reactive protein levels was demonstrated by serological tests. The pathological findings and postmortem biochemical measurements indicated that both victims died due to myoglobinuric renal failure.
2009Mechanisms of C-reactive protein-induced blood-brain barrier disruption.StrokeIncreased mortality after stroke is associated with brain edema formation and high plasma levels of the acute phase reactant C-reactive protein (CRP). The aim of this study was to examine whether CRP directly affects blood-brain barrier stability and to analyze the underlying signaling pathways.We used a cell coculture model of the blood-brain barrier and the guinea pig isolated whole brain preparation.We could show that CRP at clinically relevant concentrations (10 to 20 microg/mL) causes a disruption of the blood-brain barrier in both approaches. The results of our study further demonstrate CRP-induced activation of surface Fcgamma receptors CD16/32 followed by p38-mitogen-activated protein kinase-dependent reactive oxygen species formation by the NAD(P)H-oxidase. The resulting oxidative stress increased myosin light chain kinase activity leading to an activation of the contractile machinery. Blocking myosin light chain phosphorylation prevented the CRP-induced blood-brain barrier breakdown and the disruption of tight junctions.Our data identify a previously unrecognized mechanism linking CRP and brain edema formation and present a signaling pathway that offers new sites of therapeutic intervention.
2009[Human parvovirus B19 infection in 15 adults--two-year Toho University Hospital study].Kansenshogaku ZasshiHuman parvovirus B19 infection in adults features clinical symptoms and laboratory abnormal findings unlike those in children commonly associated with cheek rash. We diagnosed 15 adult cases based on the positive increase in anti-parvovirus B19 IgM antibody (8.89 +/- 7.86 mean +/- SD, enzyme immunoassay (EIA)). Antibody titer was measured in 78 patients clinically showing fever, edema, exanthema, arthralgia, and myalgia among 11,040 outpatients first visiting the hospital from January 2005 to December 2007. Based on clinical and laboratory findings for these 15 cases, we recommended that physicians taking anti-parvovirus B19 antibody blood samples note whether (1) the level of C reactive protein is negative or low and without leucocytosis; (2) a miliary rash is observed in short duration (rarely facial); (3) arthralgia and/or myalgia is present in the extremities (sometimes asymmetrical); (4) edema is present in the extremities, especially finger, ankle, or sole of the foot; (5) contact has been made with ill children; (6) flu-like symptoms occur such as fatigue, headache, or fever;and (7) normo- or hypocomplementemia and/or antinuclear antibody is positive. Patients who fulfill requirement (1) plus at least three of requirements (2) through (7) should have a blood sample taken. We retrospectively studied 78 cases using these requirements, finding their sensitivity to be 100% (15/15), specificity to be 88.9% (56/63), positive predictive value to be 68.1% (15/22) and negative predictive value to be 100% (56/56). These requirements are thus useful in selecting patients for measuring antibody titer and definitively diagnosing severe or persistent parvovirus B19 infection occationally observed in adults.
Bilateral non-simultaneous optic neuropathy and unilateral macular edema in a patient with POEMS syndrome.Eur J OphthalmolTo report a case of bilateral non-simultaneous optic neuropathy and unilateral macular edema in a patient with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome.A 61-year-old man with POEMS syndrome had bilateral anterior optic neuropathy and unilateral macular edema.Visual field testing showed bilateral superior altitudinal field defect. Fluorescein angiography revealed unilateral pooling of fluid consistent with cystoid macular edema. Optical coherence tomography (OCT) showed bilateral loss of retinal nerve fiber layer thickness. The erythrocyte sedimentation rate and C-reactive protein values were normal. The serum vascular growth factor measurement was elevated.This is the first reported case of ophthalmoscopic, angiographic, and OCT evidence of non-simultaneous optic neuropathy and macular edema in this syndrome. The increased vascular permeability could explain all these factors.
2008MEFV mutations modify the clinical presentation of Henoch-Schönlein purpura.J RheumatolTo investigate the prevalence of MEFV gene mutations in Turkish patients with Henoch-Schönlein purpura (HSP) but with no symptoms of familial Mediterranean fever (FMF). In addition, we assessed the clinical and laboratory characteristics of HSP patients with and without MEFV mutations.Eighty pediatric patients with HSP (44 boys and 36 girls) were enrolled. Blood for mutation analysis was obtained either at the time of the diagnosis of HSP or during followup visits in previously diagnosed patients. No patient had the diagnosis of FMF in their history and in the followup period. Exon 10 of the MEFV gene was screened, together with p.E148Q mutation analysis.Twenty-seven (34%) patients were found to be heterozygous for one of the screened MEFV mutations; p.M694V in 16, p.M680I in 5, p.V726A in 3, and p.E148Q in 3 patients. Patients with MEFV mutations were younger than those without mutations and they had edema and arthritis more frequently. Also, the frequencies of elevated erythrocyte sedimentation rate and C-reactive protein values were found to be significantly higher in patients who had MEFV mutations.Alterations in the MEFV gene are important susceptibility factors for the development of HSP and also affect the clinical presentation of it.
2008C-reactive protein, cytokines and inflammation in cardiovascular diseases.Bratisl Lek ListyInflammation of vascular cell wall is the key problem and proinflammatory cytokines and chemokines play a great role in it. These molecules, togheter with C-reactive protein (CRP) can predict risk of coronary events. It is questionable to what extend are CRP and pro-inflammatory cytokines purely acute phase markers and to what extend are they active inflammatory participants. Besides inflammation, other prominent mechanism in the pathogenesis of atherosclerosis and atherothrombosis--underlying causes of coronary events, is genetics. Gene polymorphisms including polymorphisms of inflammatory markers are studied and one of them, polymorphism of monocyte chemoattractant protein (MCP-1/CCL2) and its receptor CCR2 (key components of atherosclerosis) belong to most studied one. MCP-1/CCL2 and CCR2 polymorphisms have been implicated as susceptibility factors for chronic stable angina pectoris and myocardial infarction by several independent investigators. It seems that CCL2/CCR2 axis plays an important role both in post-ischemic and post-reperfusion inflammation and could become a new therapeutic goal in selected cardiovascular diseases as well as in stroke in future. Inhibition of this axis disrupts ischemic-reperfusion injury by decreasing edema, leucocyte infiltration and expression of inflammatory mediators. One can suppose that identifying genes influencing inflammatory biomarkers might improve understanding of genetic determinants of cardiovascular disease our management and prevention (Tab. 2, Fig. 1, Ref. 105). Full Text (Free, PDF) www.bmj.sk.
2008[Acute myocarditis after visiting Pakistan].Dtsch Med WochenschrA 42-year-old German woman presented in hospital with a high temperature (40 degrees C) after visiting Pakistan. She had manifest psychomotor retardation but no signs of meningitis, bradycardia and some pale circular erythematous skin lesions on the abdomen, which disappeared on pressure.The C-reactive protein (CRP) was 39.27 mg/dl, but the white cell count was normal. Screening tests for malaria were negative, but the blood culture grew Salmonella typhi.As typhoid fever was suspected and finally confirmed, the patient was treated with oral ciprofloxacin for 14 days. Four days after admission she had to be resuscitated, although the CRP had fallen. The underlying course of the disease was an acute myocarditis with pulmonary edema. Under intensive care complete regression of symptoms was achieved within six days. But after the antibiotic therapy had been completed the patient developed a typhoid relapse with similar but less pronounced signs and symptoms. The antibiotic treatment was changed to ceftriaxon for 14 days and complete remission of clinical, chemical and echocardiographic findings was achieved.Symptoms of high fever after visiting countries with sometimes poor hygiene should make one suspect typhoid fever, particularly when bradycardia and a normal leukocyte cell count are documented. Because of the pathophysiology of this infection different systemic complications are possible, such as acute myocarditis. Relapses are also a frequent problem: they may occur despite antibiotic treatment given according to the results of microbiological tests.
2008Exenatide as a treatment for diabetes and obesity: implications for cardiovascular risk reduction.Curr Atheroscler RepAmong the challenges in improving outcomes in patients with diabetes is effectively implementing existing pharmacotherapies. However, current therapies for diabetes are often limited by adverse effects such as edema, hypoglycemia, and weight gain. Understanding the role of the incretin effect on the pathophysiology of diabetes has led to the development of new therapeutic agents. Exenatide is the first in a new class of agents termed "incretin mimetics," which replicate several glucoregulatory effects of the endogenous incretin hormone, glucagon-like peptide-1. In clinical trials, patients with type 2 diabetes treated with exenatide demonstrate sustained improvements in glycemic control, with reductions in fasting and postprandial glucose levels and improvements in glycosylated hemoglobin levels. Improvements in glycemic control with exenatide are coupled with reductions in body weight. Lipid parameters, blood pressure, and C-reactive protein have been shown to improve favorably in patients treated with exenatide. The sustained glycemic improvements and progressive reduction in body weight with exenatide treatment support a shift toward a more favorable cardiovascular risk profile and may have a positive impact on decreasing the risk of associated long-term complications.
2008[Staphylococcal scalded skin syndrome].An Pediatr (Barc)Staphylococcal scalded skin syndrome is a rare disease caused by Staphylococcus aureus that produces exfoliative toxins. There are few epidemiological data in our environment.We present an observational cohort study. We review the cases of staphylococcal scalded skin syndrome monitored at La Paz Children Hospital during the last ten years (January 1997 to December 2006).We obtained 26 patients, 7 in the first 5 years and 19 more in the following years. The mean age at diagnosis was 19 months. Four cases (15%) occurred during the neonatal period. Sixty-seven percent of the cases were diagnosed during spring and summer. Main clinical signs were: erythroderma with blisters and posterior desquamation (100%), perioral fissures (54%), fever (46%), conjunctivitis (42%) and palpebral edema (31%). No significant increases in leukocytes (mean: 11,341/.l) or C-reactive protein (mean: 9 mg/l) were found on blood analysis. Diagnosis was made by clinical findings. S. aureus was isolated in nasal or conjunctival samples on 59% of cases. All strains were sensitive to cloxacillin, clindamycin and vancomycin. The patients were treated with cloxacillin with good progress.Staphylococcal scalded skin syndrome seems to be more common in the last few years. It must be suspected in children with acute erythroderma and perioral or conjunctival lesions. Treatment with cloxacillin leads to healing without sequelae.
2008Acute pulmonary capillary leak syndrome during elective surgery under general anesthesia.J AnesthA 75-year-old previously healthy man presented for elective resection of rectal cancer under general anesthesia. Six days before the operation, he had a high-grade fever, and elevated leukocyte count and C-reactive protein concentration, but this was resolved by an intravenous antibiotic. His condition was well controlled before the operation. Soon after the operation started, severe hypoxemia emerged, with low arterial pressure. Fiberoptic bronchoscopy demonstrated a massive amount of plasma-like edema fluid; the total amount of suctioned fluid was approximately 800 ml at the end of the surgery. This acute pulmonary edema appeared to be due to increased permeability rather than pulmonary congestion as indicated by chest radiography, pulmonary artery occlusion pressure, echocardiogram, and the protein-rich edema fluid. Elevated concentrations of the proinflammatory cytokines, interleukin (IL)-6 and IL-8, in both plasma and the pulmonary edema fluid, suggested a possible role of systemic and pulmonary inflammation in the development of this acute pulmonary capillary leak. According to the "two-hit" hypothesis, the bacterial infection preceding the operation may have primed the immune cells, and the following surgical stress may have then triggered rapid progression of acute respiratory distress syndrome. We should keep in mind that, especially following sepsis, sudden massive pulmonary capillary leak can occur during elective surgery, even though the patient's condition is well controlled.
2007[Clinical manifestations and endoscopic features of abdominal type Henoch purpura in children].Zhonghua Er Ke Za ZhiTo investigate the clinical manifestations and endoscopic features of abdominal type Henoch purpura in children and improve the diagnostic level.Retrospective review was made on the clinical, endoscopic and histopathological features of 57 cases of children with Henoch purpura abdominal type who had been hospitalized from Jan. 2002 to May 2007. Upper gastrointestinal endoscopy was performed in all cases. All the cases had various digestive system symptoms without cutaneous purpura before endoscopy. Mucosal specimens were taken from sinus ventriculi and duodenum for histopathological analysis. Helicobacter pylori (H.pylori) infection was identified by rapid urease test and histology, and diagnosis of H.pylori infection was made when both were positive.The common gastrointestinal symptoms of Henoch purpura were abdominal pain (46 cases), vomiting (32 cases), hematochezia (11 cases), diarrhea (4 cases) and abdominal distention (1 case). Three cases had arthralgia and joint swelling. The main laboratory findings were increased peripheral white blood cells (33 cases, 57.9%), 1/5 of cases had elevated C reactive protein (CRP), low serum albumin and seroperitoneum. Endoscopy demonstrated the damages to the mucosa, which varied from congestion, edema, petechia and ecchymosis (37 cases, 64.9%) to erosive and multiple ulcers (14 cases, 24.6%), granulation of mucosa in descendent duodenum (4 cases, 7.0%), and diffuse hemorrhage of mucosa (2 cases, 3.5%). The upper gastrointestinal endoscopy showed that the commonest and most serious position involved was the descendent duodenum (55 cases, 96.5%), followed by duodenal bulb (32 cases, 56.1%) and stomach (18 cases, 36.1%), esophagus was less involved (1 case, 1.8%). Histological manifestations showed swollen vascular endothelial cells of capillary vessels and small blood vessels, fibrotic necrosis of small vessels and bleeding, diffuse perivascular lymphocytic and neutrophilic infiltration and nuclear debris in mucosa and submucosa. Three cases (5.3%) were found infected with H. pylori. In 49 cases (86.0%) cutaneous purpura appeared 1 - 7 days after endoscopy. Eight cases had no cutaneous purpura until they left hospital. Two cases were lost to follow up and 6 cases (10.5%) remained free from cutaneous purpura were followed up until now (1 - 5 years).Descending duodenum is the commonest and most serious position of upper gastrointestinal tract involved in Henoch purpura. Upper gastrointestinal endoscopy with the mucosal biopsy are useful for the early diagnosis of Henoch purpura.
2008Pioglitazone reduces atherogenic outcomes in type 2 diabetic patients.J Atheroscler ThrombThe aim of this study was to evaluate the anti-atherogenic outcomes of pioglitazone, a thiazolidinedione derivative, in type 2 diabetic patients.Eight patients with poor diabetic control were treated with 15 mg of pioglitazone for 4 months. Blood samples were collected monthly, and the levels of fasting plasma glucose (FPG), HbA1c, and lipids, such as triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol, were measured. Other parameters, including immunorecative insulin (IRI), remnant-like particle-cholesterol (RLP-C), adiponectin, plasminogen activator inhibitor type 1 (PAI-1), tumor necrosis factor (TNF)- alpha , leptin, brain natriuretic peptide (BNP), and high-sensitivity (hs)-C-reactive protein (CRP), were examined at the beginning and end of the study. In addition, clinically adverse side-effects were evaluated.Treatment with pioglitazone significantly decreased the levels of HbA1c, FPG, the homeostasis model assessment of insulin resistance (HOMA-IR) index, RLP-C, PAI-1, TNF- alpha , and hs-CRP, but not the level, IRI, lipids, or leptin. In contrast, adverse side-effects, including body weight gain, liver dysfunction and edema, were not observed during this study.These results strongly suggested that treatment with pioglitazone has a greater clinical benefit for the prevention of atherosclerosis, including coronary heart diseases, without any adverse side-effects.
2008Plasmatic B-type natriuretic peptide and C-reactive protein in hyperacute stroke as markers of CT-evidence of brain edema.Int J Med SciPlasmatic B-type-natriuretic peptide (NT-PBNP) and C-reactive protein (CRP) have been reportedly elevated in stroke patients; however their clinical significance remains uncertain. The purpose of this work is to investigate whether elevation of these proteins at baseline predicts CT-evidence of brain edema.We recruited 41 consecutive patients with stroke and determined NT-PBNP and CRP at baseline (within 5 hours after onset), after 48-72 hours, and at discharge. Stroke severity was measured by means of the NIHS scale at baseline and at discharge. We also carried out brain CT at admittance and after 48 hours.There were 29 ischemic strokes and 12 hemorrhagic strokes. Evidence of brain edema on delayed scan was seen in 14 patients. Baseline levels of NT-PBNP did not predict CT-evidence of edema but CRP levels did so significantly (0.7 mg/dl in patients without edema versus 4.7 mg in patients with edema; p=0.001). Both NT-PBNP and PC levels correlated poorly to NIHSS score and increased markedly from baseline to the second determination in patients with edema. For these patients the NT-PBNP increase was 133.6 pmol/l in comparison to 1.58 pmol/l in patients without edema (p=0.002). Neither CRP nor NT-PBNP baseline levels were predictive of dependency or death.We conclude that CRP at baseline but not NT-PBNP predicts CT evidence of brain edema in stroke patients. We hypothesize that NT-PBNP levels elevated in response to edema after 48 hours of admission.
2008An autopsy case of internal jugular vein thrombophlebitis involving sepsis following blunt neck injury.J Forensic Leg MedWe report an unusual case of delayed death due to sepsis following closed blunt injury to the neck. The victim was a 71-year-old male with a clinical history of hypertension, diabetes and gout. He was found dead about three weeks after being assaulted. He had not consulted a hospital after the assault. Forensic autopsy demonstrated a large liquefied subcutaneous hematoma on the right side of the neck, peri- and thrombophlebitis of the right internal jugular vein. Otherwise, there was no evidence of trauma. Histological examination showed dermal vesicles in the skin covering the hematoma, accompanied by marked inflammatory cell infiltration phagocytosing gram-positive streptococci, subcutaneous edema, panphlebitis with partially organized thrombi and bacterial colonies, pulmonary edema and multiple pulmonary microthrombi involving bacterial aggregates. Postmortem serum C-reactive protein and neopterin levels were markedly elevated. These findings suggest sepsis as the cause of death, induced by infected internal jugular vein thrombophlebitis following blunt neck injury involving impaired skin barrier.
2007[An elderly woman with duodenal perforation difficulty diagnose].Nihon Ronen Igakkai ZasshiAn 86-year-old woman was referred with acute epigastric pain. She had tenderness, but no muscular guarding of the epigastric lesion. Abdominal ultrasound showed a gallstone with a normal gallbladder wall and no ascites. The white blood cell count was 11,600/mm(3), but she was negative for C-reactive protein (CRP). An upper gastrointestinal tract endoscopic examination revealed only edema of the duodenal mucosa. Although H2-receptor antagonists were given, she had to be admitted due to chills and high fever. While the abdominal symptoms did not change, the CRP concentration became 14.79mg/dl. While plain abdominal X-ray did not show an abnormal gas pattern, subsequent abdominal CT examination showed air and fluid collection around the second portion of the duodenum. We diagnosed duodenal perforation and prepared for emergency operation. However, her general condition had markedly deteriorated during the hours. Laparotomy revealed a free purulent fluid around second portion of the duodenum caused by perforation of a duodenal diverticulum. The patient gradually recovered and was discharged after 58 days. Since a duodenal perforation in an elderly patient is difficult to diagnose early in spite of serious illness, abdominal CT should be encouraged.
2008Pulmonary edema after extensive radiofrequency ablation for atrial fibrillation.J Cardiovasc ElectrophysiolMore extensive ablation strategies for the treatment of atrial fibrillation (AF) have increased success rates but are associated with new and sometimes serious complications. We describe a new complication after extensive radiofrequency (RF) ablation in the left atrium (LA) for persistent AF.Electroanatomic guided circumferential ablation around both ipsilateral pulmonary veins (PV) was performed with the endpoint of complete conduction block. When necessary, supplementary RF applications were added, including ablation of complex fractionated potentials and/or isolation of other thoracic veins and/or linear left atrial lesions. RF energy was delivered via an irrigated tip catheter with a maximum power of 30-35 W. Four out of 120 patients undergoing extensive RF ablation for persistent AF (including two patients with additional LA substrate modification) developed dyspnea, bilateral pulmonary edema, and signs of a systemic inflammatory response syndrome (SIRS) (rise in body temperature, leukocyte count, and C-reactive protein (CRP levels) 18-48 hours after the procedure. There were no signs of PV stenosis, focal lung injury, left ventricular dysfunction, circulatory failure, or infection. All patients had complete recovery with supportive therapy within 3-4 days after the onset of symptoms.Extensive LA radiofrequency ablation bears the risk of a severe pulmonary edema. Although the precise mechanism is elusive, clinical features point toward a systemic inflammatory response.
2008On the importance of pedal edema in hemodialysis patients.Clin J Am Soc NephrolVolume control is a key component of treatment of hemodialysis patients. The role of pedal edema as a marker of volume is unknown. The objective of this study was to determine factors that are associated with edema.A cross-sectional study of asymptomatic hemodialysis patients (n = 146) in four university-affiliated hemodialysis units was conducted. Echocardiographic variables, blood volume monitoring, plasma volume markers (plasma renin and aldosterone and N-terminal pro B-type natriuretic peptide), and inflammation markers (C-reactive protein and IL-6) were measured as exposures, and edema was measured as outcome.In a multivariate logistic regression analysis, age, body mass index, and left ventricular hypertrophy were independent determinants of edema. Compared with patients with normal or low weight, overweight patients had odds ratio for edema of 5.7 (95% confidence interval [CI] 1.0 to 31.8), and obese patients of 44.8 (95% CI 9.0 to 223). Patients in the top quartile of left ventricular mass index and normal to low weight had odds ratio of edema of 7.7 (95% CI 2.3 -25.9), those who were overweight of 43.5 (95% CI 3.9 to 479.8), and those who were obese of 344.8 (95% CI 33.8 to 3515). Inferior vena cava diameter, blood volume monitoring, plasma volume markers, and inflammation markers were not determinants of edema.Pedal edema correlates with cardiovascular risk factors such as age, body mass index, and left ventricular mass but does not reflect volume in hemodialysis patients.
2007A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of the efficacy and tolerability of combination therapy with rosiglitazone and sulfonylurea in African American and Hispanic American patients with type 2 diabetes inadequately controlled with sulfonylurea monotherapy.Clin TherType 2 diabetes mellitus is twice as prevalent in African Americans and Hispanic Americans as in non-Hispanic whites. However, the effectiveness and safety profile of rosiglitazone maleate used as combination therapy with sulfonylureas in the management of diabetes and its effect on cardiovascular disease (CVD) biomarkers/parameters have not been studied in these populations.The purpose of this study was to determine the efficacy and tolerability of the addition of rosiglitazone to a regimen of glyburide once daily in African American and Hispanic American patients with type 2 diabetes previously inadequately controlled with sulfonylurea monotherapy.This randomized, double-blind, placebo-controlled, parallel-group study was conducted at 38 centers in the United States. Eligible patients were aged < or =21 years, had type 2 diabetes, a fasting plasma glucose (FPG) level > or =140 mg/dL, and a glycosylated hemoglobin (HbA(1c)) value > or =7.5%, and had been treated with sulfonylurea monotherapy for at least 2 months before screening. Patients were assigned to receive treatment with glyburide 10 or 20 mg/d plus rosiglitazone 8 mg (GLY+RSG) or placebo (GLY+PBO) PO (tablets) QD for 24 weeks. The primary efficacy end point was the change from baseline in HbA(1c) after 24 weeks of treatment. Secondary end points included change in FPG; proportion of patients achieving HbA(1c) targets (<7.0% and <6.5%); and changes in biomarkers for CVD risk, including C-reactive protein (CRP), plasminogen activator inhibitor (PAI)-I activity, fibrinogen, tissue plasminogen activator (tPA) antigen, von Willebrand factor (vWF), soluble vascular cell adhesion molecule (sVCAM), lipoprotein-associated phospholipase A 2 activity, and urinary albumin/creatinine ratio (UACR). Tolerability was assessed using physical examination, including vital-sign measurement, clinical laboratory tests, and adverse event (AE) reports collected at each study visit.A total of 245 patients (101 African American and 144 Hispanic American) were enrolled. Demographic characteristics were comparable between the GLY+RSG and GLY+PBO groups: mean (SD) age (52 [11.9] vs 53 [10.4] years), HbA(1c) (9.2% [1.3%] vs 9.4% [1.4%]), sex (men/women, 45.3%/54.7% vs 48.3%/51.7%), race (African American/Hispanic American, 43.6%/56.4% vs 37.9%/62.1%), and mean (SD) weight (86.3 [18.8] vs 88.3 [19.4] kg). In the overall study population, treatment with GLY+RSG was associated with a significantly greater mean (95% CI) reduction from baseline in HbA(1c) compared with GLY+PBO (between-group Delta, -1.4% [-1.7% to -1.1%]; P < 0.001). When assessed by ethnicity, HbA(1c) values were significantly reduced with GLY+RSG compared with GLY+PBO in African American patients (between-group Delta, -1.4%) and in Hispanic American patients (between-group Delta, -1.5%) (both, P < 0.001), as were FPG levels (between-group Deltas, -3.1 mmol/L [57 mg/dL] and -3.8 mmol/L [-69 mg/dL], respectively; both, P < 0.001). With GLY+RSG, 9151 (17.6%) African American patients and 17/66 (25.8%) Hispanic American patients achieved HbA(1c) <7%, compared with 2/44 (4.5%) and 1/72 (1.4%) patients, respectively, who achieved this goal with GLY+PBO. Homeostasis model assessment estimates of insulin sensitivity and beta-cell function were significantly improved with GLY+RSG compared with GIX+PBO (between-group Deltas, 29.3% and 78.4%, respectively; both, P < 0.001). With regard to CVD biomarkers, there were potentially deleterious changes compared with baseline in the GLY+PBO group for CRP (+29.4%; P = 0.042), PAI-1 activity (+27.0%; P = 0.006), fibrinogen (+15.7%; P = 0.007), and sVCAM (+7.0%; P = 0.035), whereas there were no significant increases in these factors in the GLY+RSG group. In the GLY+RSG group, there were significant improvements in tPA (-17.8%; P < 0.001), vWF (-11.3%; P = 0.019), and UACR (-17.2%; P = 0.028) over 24 weeks' treatment, whereas there were no significant changes in any of these factors in the GLY+PBO group. As a result, significant treatment effects were observed for CRP (-29.2%; P = 0.019), tPA (-18.4%; P < 0.001), vWF (-12.9%; P < 0.015), and UACR (-26.7%; P = 0.006) with GLY+RSG compared with GLY+PBO. The most frequently reported AEs with GLY+RSG were edema and weight increase (both 121121 [9.9%] patients) and with GLY+PBO were upper respiratory tract infection (18/124 [14.5%] patients). AEs were reported in 83/121 (68.6%) patients in the GLY+RSG group, of which 6/121 (5.0%) were assessed as severe, compared with 70/124 ( 56.5 % ) patients who received GLY+PBO, of which 31124 (2.4%) were assessed as severe.Add-on rosiglitazone administered for 24 weeks was effective and well tolerated in these African American and Hispanic American patients with type 2 diabetes previously inadequately controlled on sulfonylurea monotherapy.
2008Miniaturized cardiopulmonary bypass system in neonates and small infants.Interact Cardiovasc Thorac SurgCardiopulmonary bypass (CPB) in children is associated with a capillary leak due to inflammatory response, which results in an increase in total body water. This study was designed to reveal that our miniaturized CPB system reduced the peri-operative systemic inflammatory response in small infants. In our institution, the priming volume has been reduced from 500 ml to 140 ml currently. Eighty consecutive patients weighing <5 kg were retrospectively reviewed. The postoperative peak C-reactive protein (CRP), body weight gain (%BWG), and the duration of postoperative mechanical ventilation (MVT) data were collected for each patient. Stepwise multiple logistic regression analyses were used to investigate which of the factors most affected the peri-operative inflammatory responses. A priming volume (coefficient: 0.060, P=0.01), most affected the postoperative peak CRP (mg/dl). A combination of priming volume (coefficient: 0.015, P=0.006), and bypass time (coefficient: 0.013, P=0.028), most affected %BWG (%). A combination of priming volume (coefficient: 0.05, P=0.001) and age (coefficient: -0.02, P=0.001) most affected the MVT (days). The miniaturized circuits reduced the peri-operative inflammatory response, resulting in reduced postoperative systemic edema, and postoperative mechanical ventilation time.
2007[Research on the clinical features and effective factors of 249 diabetic patients with deep foot infection].Zhonghua Yi Xue Za Zhi249 diabetic patients with deep foot infection were retrospectively studied. Their clinical features and effective factors related to wound healing were analyzed.249 patients team (physician, surgeon and diabetes-specific nurse) were divided into 3 groups. Group A: patients healed without amputation (n = 107), group B: patients healed after amputation (n = 114), and group C: patients didn't heal after amputation. All patients' clinical features, lab examinations and foot wound features were compared.The group A patient were (59 +/- 12) years old, significantly younger than the group B (67 +/- 11, P < 0.01). Hypersensitive C reactive protein (hs-CRP, 18 +/- 5 mg/L) and plasma albumin (32 +/- 7 g/L) of group A were significantly higher than those of group B (13 +/- 5 mg/L and 29 +/- 5 g/L, respectively, P < 0.01). The duration of diabetes mellitus of group B (17 +/- 11) year was significantly longer than that of group A (10 +/- 6 year, P < 0.05). The possibility of probing bone, purulent secretion, necrosis, bone exposure, cacosmia, edema and critical limb ischemia of group B were more frequent (P < 0.01 or P < 0.05) compared to group A. The age of group B (67 +/- 11) are younger than that of group C (72 +/- 9, P < 0.05). In group B, temperature (38.1 +/- 1.1) degrees C, white blood cell (WBC) count (10 +/- 3) x 10(9)/L and hs-CRP (13 +/- 5) mg/L were higher than those of group C (37.4 +/- 0.8 degrees C, 8 +/- 2 x 10(9)/L and 7 +/- 6 mg/L, respectively, all P < 0.05). Critical limb ischemia of group B (37%) was more frequent than that of group A (7%, P < 0.05), but less frequent than that of group C (77%, P < 0.01). hs-CRP and plasma albumin were protective factors for wound healing. Age, the possibility of probing bone, purulent secretion, necrosis, bone exposure, cacosmia, edema and critical limb ischemia were risk factors for wound healing.diabetic patients with deep foot infection are difficult to be diagnosed in early stage since they often have no significant clinical syndrome such as fever, redness, swelling and pain, and their WBC count does not increase. Though multidisciplinary team manages these patients, more than half of them need amputation. Wound healing in the patients is related to multiple factors, including age, duration of diabetes mellitus, hs-CRP, plasma albumin, WBC count, level of limb ischemia and wound features.
2008Increased plasma levels of inflammatory markers and upper airway resistance during sleep in pre-eclampsia.Sleep MedTo evaluate pregnancy-associated sleep disorders, pregnancy outcomes and inflammatory markers in pre-eclampsia and normal pregnancy (control).We studied 15 consecutive pre-eclamptic women and 14 controls. Pre-eclamptic women underwent overnight pulse oximetry and nasal pressure measurements at a university teaching hospital, and the sleep study for the controls was performed at home. Mean gestation was 31 weeks. Nasal airflow was carefully analyzed visually, and the time with flow limitation was calculated as a percentage of total recording time. At the time of the sleep study, the subjects were clinically evaluated, they answered sleep questionnaires, and fasting blood samples were drawn for tumor necrosis factor alpha TNF-alpha, interleukin 6 (IL-6) and sensitive C-reactive protein. Pregnancy outcomes were collected after delivery.Pre-eclampsia patients spent significantly more time with flow limitation (mean+/-SD: 21+/-18% vs. 4+/-9%), had higher plasma levels of TNF-alpha (6.2+/-2.3 ng/l vs. 4.1+/-ng/l) and IL-6 (4.4+/-ng/l vs. 1.2+/-0.4 ng/l), had more generalized edema, had increased fatigue and snoring, and had poorer pregnancy outcomes than did controls. Age, gestational age, mean SpO2 and body mass index did not differ between the groups.Pregnant women with pre-eclampsia showed significantly more nasal flow limitation during the night, higher fasting IL-6 and TNF-alpha plasma levels, more edema and worse pregnancy outcomes than did healthy pregnant women.
2007Bone edema determined by magnetic resonance imaging reflects severe disease status in patients with early-stage rheumatoid arthritis.J RheumatolTo determine the significance of bone edema, detected by magnetic resonance imaging (MRI), in early-stage rheumatoid arthritis (RA).We simultaneously examined serologic variables, MRI of wrist sites and finger joints of both hands, clinical disease activity score (DAS), and HLA-DR typing at entry in 80 patients with early-stage RA.The number of bones scored as positive for bone edema correlated with the number of sites scored as positive for MRI synovitis and MRI bone erosion, rate of enhancement (E-rate), and serum C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and interleukin 6 (IL-6). Findings for MRI synovitis and MRI bone erosion, E-rate, CRP, MMP-3, IL-6, seropositivity, and titer of anti-cyclic citrullinated peptide antibody (anti-CCP antibody), DAS28-CRP and HLA-DRB1*0405 allele carriership, were significantly higher in the positive versus the negative bone edema group.Bone edema based on our scoring system may reflect severe disease status in patients with early-stage RA. However, its clinical value at entry in prognostication of RA should be examined through prospective clinical followup studies.
2008Effect of pioglitazone on heart function and N-terminal pro-brain natriuretic peptide levels of patients with type 2 diabetes.Acta DiabetolWe assessed the effect of the addition of pioglitazone on metabolic control and heart function of patients with type 2 diabetes already receiving sulfonylurea plus metformin. Forty-four patients were given 30 mg of pioglitazone for 3 months. Physical examination, laboratory tests including N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiography, were performed at baseline and at study completion. Target HbA(1c) levels were achieved by 44.2% of the patients. Pioglitazone ameliorated lipid profile and lowered liver enzymes and C-reactive protein. Significant increases in NT-proBNP by 39% (P < 0.005) were noticed, but echocardiographic parameters were not altered, even in high-risk subgroups (patients older than 60 years, with diabetes for more than 10 years, with hypertension, with elevated baseline NT-proBNP levels, with left ventricular hypertrophy). In patients with a greater than 60% increase in NT-proBNP levels, a significant increase in left ventricular ejection fraction (P < 0.05) and in fractional shortening (P < 0.05) was found. None of the patients developed edema or signs or symptoms of heart failure. Triple oral combination antidiabetic treatment is an effective therapeutic strategy and weight gain does not abrogate its beneficial actions. Pioglitazone does not affect heart function and even though it increases NT-proBNP, this appears to represent a reaction to volume overload.
2008The effects of contrast agent and intraductal pressure changes on the development of pancreatitis in an ERCP model in rats.Langenbecks Arch SurgAlthough there are various experimental pancreatic models in animals, only a few studies have evaluated how intraductal pressure and contrast agent affect the development of pancreatitis after endoscopic retrograde cholangiopancreatograpy (ERCP).The rats were randomly divided into seven groups (n = 8/group). The rats in all groups underwent laparotomy and their biliopancreatic ducts were cannulated transduodenally using a 24G catheter. In the control group, group 1, the biliopancreatic ducts of the rats were not infused with any fluid. The biliopancreatic ducts of the rats in groups 2, 3, and 4 were infused with 0.5 ml isotonic NaCl solution at 10, 2, and 50 mmHg, respectively. Groups 5, 6, and 7 were given 0.5 ml of 50% diluted contrast agent at 10, 25, and 50 mmHg, respectively. The serum amylase, aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and C-reactive protein (CRP) were measured 24 h after the procedure. Pancreatic tissue was also evaluated histopathologically.Pancreatitis due to the contrast agent was noted when comparing the low pressure isotonic NaCl group and the low pressure contrast group (p < 0.05). Based on serum amylase and CRP values, there was a positive correlation between the severity and frequency of acute pancreatitis and pressure (p < 0.01). AST and LDH levels increased in all of the groups that underwent the procedure; however, no correlation was detected with increasing pressure or with the use of contrast agent (p > 0.05). Both pancreatic edema and the inflammatory cell infiltration score were elevated in isotonic NaCl and contrast group (p < 0.05); however, necrosis was not significantly changed (p > 0.05).The results of this study suggest that the main mechanism for preventing pancreatitis after ERCP is to minimize trauma to the pancreatic canal, to cannulate the pancreas only when it is necessary, and to give contrast agent under low pressure when it is needed.
2007Low-dose rosiglitazone in patients with insulin-requiring type 2 diabetes.Arch Intern MedThe objective was to compare the efficacy and safety of adding low-dose rosiglitazone (2 or 4 mg/d) to insulin therapy vs continued insulin monotherapy in patients with type 2 diabetes mellitus who were unable to achieve glycemic control with insulin therapy alone.In this 24-week, double-blind study, 630 individuals with type 2 diabetes mellitus that was inadequately controlled with insulin therapy alone were randomized to treatment with rosiglitazone (2 or 4 mg/d) or placebo in combination with ongoing insulin therapy. The dosage of insulin therapy could be adjusted at the investigator's discretion if required for hypoglycemia or additional glycemic control.The addition of rosiglitazone (2 or 4 mg/d) to insulin therapy significantly decreased mean glycated hemoglobin concentrations compared with placebo plus insulin (-0.3% [P=.02] and -0.4% [P<.001]) and compared with baseline (-0.6% and -0.8% [both P<.001]) after 24 weeks. The addition of 2 or 4 mg/d of rosiglitazone significantly decreased the C-reactive protein level (vs baseline: -22.0% [P<.001] and -34.2% [P<.001]; vs placebo: -22.2% [P=.003] and -32.0% [P<.001]) and fibrinogen (vs baseline: -10.5% and -12.0% [both P<.001]; vs placebo: -7.9% [P=.002] and -7.6% [P=.004]), while 4 mg/d of rosiglitazone significantly reduced matrix metalloproteinase 9 levels (vs baseline: -17.1% [P=.007]; vs placebo: -23.3% [P<.001]). The adverse event profile, including incidence of hypoglycemia and edema, was similar between treatment groups, and most adverse events were mild to moderate in intensity.The addition of low-dose rosiglitazone to insulin therapy is an effective and well-tolerated treatment option for patients with type 2 diabetes mellitus who continue to have poor glycemic control despite administration of exogenous insulin as monotherapy.clinicaltrials.gov Identifier: NCT00054782.
2007Stroke biomarkers: can they help us to guide stroke thrombolysis?Timely Top Med Cardiovasc DisThe use of blood biomarkers is getting increasingly popular in the field of cerebrovascular diseases, since biomarkers might aid physicians in several steps of stroke evaluation. We will discuss whether stroke diagnosis might be possible using some specific brain biomarkers and if this approach will permit rapid referral of stroke patients to hospitals with acute treatments such as tissue plasminogen activator (t-PA) available. Although thrombolytic therapy in acute stroke is effective since it accelerates clot lyses and earlier restoration of blood flow, up to 40-50% of treated patients do not recanalize or do it too late, and between 6 and 15% suffer hemorrhagic transformations with high death rates. In the context of the neurovascular unit, t-PA may degrade extracellular matrix integrity and increase risks of neurovascular cell death, blood-brain barrier leakage, edema and hemorrhage. In humans, biomarkers such as matrix metalloproteinase-9 (MMP-9) or fibronectin, which might be used to select patients at higher risk of hemorrhagic transformation, and high plasminogen activator inhibitor-1 (PAI-1) interfering with tPA-induced recanalization, thus predicting clot-lyses resistance and poor outcome, have been recently identified. Moreover, high levels of MMP-9 and MMP-13 are involved in DWI lesion growth in spite of thrombolytic therapy suggesting its ultra-early role in brain injury. Other biomarkers such as C-reactive protein may accurately predict stroke mortality following reperfusion therapies. Finally, we will also show that genetic background of stroke patients may condition plasma levels of some of these biomarkers and influence therapeutic response in t-PA-treated patients.
2007Long-term oral sodium bicarbonate supplementation does not improve serum albumin levels in hemodialysis patients.Nephron Clin PractMetabolic acidosis, a frequent event in hemodialysis patients, has been implicated as a potential cause of protein-energy malnutrition. Unfortunately, correction of metabolic acidosis by means of high bicarbonate concentration in the dialysate does not seem to lead to significant changes in nutritional parameters. The project was a single-arm, open-label, 12-month pilot study at a university-based tertiary care center aimed at evaluating whether correction of metabolic acidosis through long-term oral sodium bicarbonate supplementation improves serum albumin levels and other nutritional parameters in patients undergoing maintenance hemodialysis. Twenty highly acidotic hemodialysis patients patients were invited to consume an oral supplementation of sodium bicarbonate (1 g, thrice daily), for 12 months. Patients were followed at baseline and every month, until month 12. At each follow-up visit, dry body weight, BMI, blood pressure, presence of edema, venous bicarbonate, and serum albumin were measured. Total lymphocyte count, fasting total cholesterol and C-reactive protein were assessed every 2 months. At baseline and at 12 months, the subjective global assessment of nutritional status and the protein equivalent of nitrogen appearance normalized to actual body weight were determined. Plasma bicarbonate level rose from 18.1 +/- 2.7 to 22.1 +/- 4.5 mmol/l after 10 months (p = 0.001). Mean serum albumin levels were 3.8 +/- 0.2 mg/dl at baseline and 3.9 +/- 0.2 at the end of the study. Repeated measure ANOVA showed that there was no significant effect of bicarbonate treatment on serum albumin levels (p = 0.29), dry weight (p = 0.1), serum total cholesterol (p = 0.97), total lymphocyte count (p = 0.69), or C-reactive protein (p = 0.85). Mean subjective global assessment score was 4.53 +/- 0.37 at baseline and 4.58 +/- 0.54 at 12 months (p = 0.1). Mean nPNA (g/kg/day) was 0.86 +/- 0.05 at baseline and 0.85 +/- 0.08 at month 12. The present study demonstrates that long-term oral sodium bicarbonate at the dose of 1 gram thrice daily has no significant effect on nutritional status of HD patients.
2007Therapeutic effects of Saireito (TJ-114), a traditional Japanese herbal medicine, on postoperative edema and inflammation after total hip arthroplasty.PhytomedicineSaireito (TJ-114) is a traditional Japanese herbal medicine that has been used for treating edema and inflammation in diseases such as nephritic disease. This study investigates the effect of TJ-114 on postoperative edema and inflammation after total hip arthroplasty (THA). Patients who underwent cementless THA were randomly divided into two groups: Group A consisted of 8 hips of 8 patients who were treated with TJ-114 at a dose of 9 g/day 2 days before surgery and for 2 weeks after surgery; Group B consisted of 9 hips of 9 patients who did not take TJ-114. Although no significant difference was observed between the two groups for lower extremity edema, it was found that swelling of the proximal leg in Group A was less than that in Group B. Furthermore, 3 weeks after surgery, every measuring point in the lower extremity showed that TJ-114 tended to decrease postoperative swelling compared to measurements of swelling of patients who did not take TJ-114. Serum C-reactive protein (CRP) levels of 6 out of 8 patients in Group A decreased and became negative 2 weeks after surgery; however, there were no patients in Group B whose CRP levels became negative after 2 weeks. In conclusion, TJ-114 is safe and useful for the prevention and early recovery of postoperative leg edema after THA with an association of rapid CRP reduction.
2007["Free" iron, transferrin and ferritin levels in serum and their relation with severe malnutrition].An Pediatr (Barc)"Free" serum iron has been associated with the development of edema in Kwashiorkor-type severe acute malnutrition.A descriptive, cross sectional study was performed. Twenty-four children with edematous malnutrition, 22 with marasmus and 20 without malnutrition were compared. "Free" iron, transferrin, saturation index and attachment capacity of iron, ferritin, total protein, albumin, total iron, and C-reactive protein (CRP) were determined in serum.A significant difference was found between malnourished children with "free" serum iron and the control group in which "free" iron was not found. However, no significant differences were found in "free" serum iron levels between marasmatic and edematous children. Transferrin was negatively correlated with "free" iron (r=-0.519; p=0.000). Total proteins, albumin and transferrin were all significantly lower in children with edema than in those with marasmus. A low transferrin level and a high saturation index could be used to estimate the probability of edema in 67.5% of cases (p=0.001).Severe acute malnutrition was associated with the presence of "free" serum iron both in children with marasmus and in those with edema. "Free" iron does not explain the presence of edema but, as with severe hypoalbuminemia, the concurrence of a low transferrin level and a high saturation index may contribute to the etiology of edema.
2006Stroke biomarkers: Can they help us to guide stroke thrombolysis?Drug News PerspectThe use of blood biomarkers is getting increasingly popular in the field of cerebrovascular diseases, since biomarkers might aid physicians in several steps of stroke evaluation. We will discuss whether stroke diagnosis might be possible using some specific brain biomarkers and if this approach will permit rapid referral of stroke patients to hospitals with acute treatments such as tissue plasminogen activator (t-PA) available. Although thrombolytic therapy in acute stroke is effective since it accelerates clot lyses and earlier restoration of blood flow, up to 40-50% of treated patients do not recanalize or do it too late, and between 6 and 15% suffer hemorrhagic transformations with high death rates. In the context of the neurovascular unit, t-PA may degrade extracellular matrix integrity and increase risks of neurovascular cell death, blood-brain barrier leakage, edema and hemorrhage. In humans, biomarkers such as matrix metalloproteinase-9 (MMP-9) or fibronectin, which might be used to select patients at higher risk of hemorrhagic transformation, and high plasminogen activator inhibitor-1 (PAI-1) interfering with tPA-induced recanalization, thus predicting clot-lyses resistance and poor outcome, have been recently identified. Moreover, high levels of MMP-9 and MMP-13 are involved in DWI lesion growth in spite of thrombolytic therapy suggesting its ultra-early role in brain injury. Other biomarkers such as C-reactive protein may accurately predict stroke mortality following reperfusion therapies. Finally, we will also show that genetic background of stroke patients may condition plasma levels of some of these biomarkers and influence therapeutic response in t-PA-treated patients.
2006[Levels of fibrinogen compared to crp in plasma as new marker in diagnosis of pulmonary edema of non septic origin].HarefuahCommunity-acquired pneumonia, that requires hospitalization, is a severe illness with high mortality rates, especially in cases of delay of appropriate treatment. At times, the correct diagnosis of the disease is difficult due to equivocal clinical picture or chest film, accompanying diseases that could mask or simulate the pneumonia.1. follow-up levels of fibrinogen throughout hospitalization in the group of patients admitted to the hospital due to pneumonia and pulmonary edema of non-infectious origin; 2. an estimation opportunity using them as possible new markers for diagnosis of pneumonia and for following response to treatment.Three groups of patients were studied: a group of 15 patients admitted due to pneumonia, a group of 15 patients admitted due to pulmonary edema, and a control group 15 healthy subjects. The blood samples for white blood cells count, erythrocyte sedimentation rates, levels of fibrinogen, C-reactive protein, albumin, were taken for each patient on admission, 48 and 72 hours following admission and on discharge day. The received dates were compared using Student t-test.The levels of fibrinogen were higher on admission, in the patients with pneumonia, maximally after 48 and 72 hours (P<0.001) in comparison to the control group. In pulmonary edema the fibrinogen levels were also high but less than those with pneumonia (P=0.0044), with gradual declining throughout hospitalization period (P> 0.027 for both groups in discharge day). The comparison of fibrinogen levels between groups of patients with pneumonia and pulmonary edema reveal statistically significant results at time of admission, after 48 and 72 hours but not on discharge day.Fibrinogens can be used as reliable markers for primary diagnosing of pneumonia or differential diagnosis from pulmonary edema, on admission and until 72 hours but not for patient follow-up throughout hospitalization period. Additional studies are needed for discovering other new markers for patient follow-up throughout hospitalization period.
2006MRI of the sacroiliac joints in patients with moderate to severe ankylosing spondylitis.AJR Am J RoentgenolThe objectives of our study were to evaluate whether MRI findings of the sacroiliac joints are able to distinguish between active and inactive disease in patients with established ankylosing spondylitis and to determine whether these findings correlate with markers of clinical activity, disease duration, severity, and degree of radiographic damage.Eighteen patients with symptomatic moderate to severe ankylosing spondylitis were evaluated. MRI of the sacroiliac joint (1.5 T) was performed using fat-saturated T2-weighted, T1-weighted, STIR, and fat-saturated contrast-enhanced T1-weighted sequences. The sacroiliac joints were evaluated by two radiologists for enhancement, subchondral bone marrow edema, erosions, and subchondral fatty marrow infiltration. Findings on MRI were analyzed for correlation with multiple clinical characteristics and measures of disease activity, including radiographic scoring.In 17 patients, MRI showed abnormal findings of the sacroiliac joint. Ten patients showed active disease on MRI as measured by abnormal enhancement and subchondral bone marrow edema. Disease activity detected using MRI correlated in a positive fashion with only C-reactive protein (CRP) level. There was no correlation with the other measures of disease activity or with disease duration. In 14 patients, fatty subchondral bone marrow was detected on MRI. These changes were seen in patients with active and chronic disease and correlated with higher radiographic scores but not with disease duration or markers of disease activity.Contrast-enhanced MRI of the sacroiliac joint is sensitive in depicting sacroiliitis in patients with established ankylosing spondylitis. Subchondral edema and enhancement correlate with high CRP levels. Subchondral fatty bone marrow changes were seen in both active and chronic sacroiliitis and are correlated with higher radiographic scores; these changes may be a marker of more advanced disease.
2006Spinal tuberculosis: a longitudinal study with clinical, laboratory, and imaging outcomes.Semin Arthritis RheumTo study imaging changes associated with spinal tuberculosis (ST) over time and evaluate their association with clinical and laboratory data.Between 1997 and 2004, patients with proven ST in our institution were prospectively enrolled and treated for 1 year. Clinical and laboratory data were collected at baseline and every 3 months. Computed tomography (CT) and magnetic resonance imaging (MRI) were performed at baseline. MRI was performed at least twice during treatment and at the end of treatment.Nineteen patients were enrolled; neurological signs were present at baseline in 14 patients (74%). Initial MRI/CT findings comprised (in percentages of patients) the following: paravertebral abscesses (100/100); intradiscal abscesses (47/0); and epidural abscesses (82/24) with spinal cord compression (64/18) or radicular compression (36/0). Edema of the vertebral body was observed on initial MRI in all the patients. Full follow-up data were available for 15 patients: all were cured with a mean follow-up of 25 months after the end of treatment. Weight gain was nearly maximal at 6 months, and pain relief was achieved within 9 months. C-reactive protein returned to normal after 3 months. On MRI, all epidural abscesses disappeared within 9 months; paravertebral abscesses disappeared after 3, 6, and 12 months in 45, 50, and 85% of patients, respectively. Vertebral body signal converted to a fatty signal in 75% of cases at 12 months.Significant imaging abnormalities can persist after successful treatment of ST. These findings suggest that MRI need not be repeated in patients with clinical and laboratory improvement.
2006Pulmonary involvement in Sweet's syndrome: a case report and review of the literature.Int J DermatolPulmonary involvement in Sweet's syndrome (SS) is rare. We report a case of SS with severe respiratory involvement responding to corticosteroid therapy. A 82-year-old man presented fever of 39 degrees C associated with cough and dyspnea, and crackles in the left lung. The infection work-up was negative. Chest X-ray showed cardiomegaly and left lower lobe pulmonary infiltrates. Pulmonary signs did not improve on treatment with antibiotics, and after 1 week maculopapular lesions appeared, localized on the knees, the periombilical area and the back. The antibiotics were changed without improvement. A skin biopsy revealed infiltration by neutrophilic granulocytes and marked edema in the dermis, consistent with SS. The patient's condition progressively worsened, requiring high oxygenotherapy, and he was transferred to an intensive care unit. Chest X-ray revealed an important alveolar and interstitial syndrome. Bronchoalveolar lavage found 170 leukocytes with 30% neutrophils (N < 5%), 7% lymphocytes and 63% macrophages. A search for bacteria, viruses or parasites in bronchoalveolar lavage was negative. The patient was treated with antibiotics, a high dose of furosemide and steroids for 4 days. Because the patient improved dramatically within 5 days, with a negative infection work-up and a dramatic decrease of C-reactive protein, the antibiotics were stopped. Steroids were secondarily tapered very slowly. A chest computed tomography (CT) scan showed a substantial improvement of pulmonary lesions. We also review the 22 cases of pulmonary involvement of SS reported in the literature.
2006A case of recurrent Sweet's syndrome in an 80-year-old man: a clue to an underlying malignancy.Int J DermatolAn 80-year-old man presented with multiple erythematous papules on the trunk and extremities of a few weeks' duration. He had no past medical or family history of skin diseases or any other medical diseases. A biopsy showed a perivascular lymphohistiocytic infiltrate and sparse neutrophils with several atypical lymphocytes in the deeper dermis. With an initial diagnosis of T-cell pseudolymphoma or unspecified neutrophilic dermatosis, he showed a brisk response to an intramuscular injection of triamcinolone acetonide (40 mg/mL). After 1 month, his skin lesion recurred. Steroid was given with a good clinical response. One month later, however, his skin lesion relapsed. At this time, he presented with disseminated pustulopapular lesions on the trunk and extremities. Examination revealed multiple, variable-sized, erythematous plaques with central pustules on the extremities (Fig. 1). The mucous membranes were not involved. He had no pain or tenderness. He had no systemic symptoms. Laboratory tests showed a hemoglobin level of 10.3 g/dL, a leukocyte level of 6,900/mm(3), with an increased proportion of segmented nuclear neutrophils (83%), and an elevated C-reactive protein. A skin biopsy revealed a dense perivascular and interstitial infiltrate composed of neutrophils with marked dermal edema (Fig. 2). Sweet's syndrome was the final diagnosis and he was treated with oral prednisolone (30-40 mg/day) and dapsone (50 mg/day) for 2 months. As this 80-year-old patient had a recurrent history of similar skin lesions and anemia, an underlying hematologic malignancy was suspected. A bone marrow biopsy showed typical myelodysplastic syndrome (MDS). The hemoglobin level was decreased to 5.3 g/dL during a follow-up period of 5 months. The skin lesions recurred despite oral steroids and dapsone. The patient received only symptomatic treatment, such as a transfusion, for the underlying malignancy MDS.
2006Rapidly progressive glomerulonephritis in a patient with Chlamydia pneumoniae infection: a possibility of superantigenic mechanism of its pathogenesis.Clin NephrolHerein we describe a case of a patient with rapidly progressive glomerulonephritis after Chlamydia pneumoniae infection. An 88-year-old woman who had had C. pneumoniae infection two months previously was admitted to our hospital with complaints of dyspnea and generalized edema. Laboratory tests revealed acute renal failure, polyclonal hypergammaglobulinemia, highly increased level of C-reactive protein, and hematoproteinuria. A renal biopsy revealed mesangial and endocapillary proliferative glomerulonephritis with crescents. She responded to high-dose steroids, cyclophosphamide, minocycline, and plasma exchange treatment with the remission of oliguric renal failure. The percentage of the subset of CD3+ TCR+ Vbeta11+ cells markedly increased to 9.6% (normal range: < 1.04%) at the onset of the disease and decreased to 0.1% after the treatment. These clinicopathological features were similar to those of superantigen-associated glomerulonephritis after methicillin-resistant Staphylococcus aureus infection. We suggest that the superantigenic mechanism is one of the possible pathomechanisms of this glomerulonephritis.
2006Anti-inflammatory effect of Houttuynia cordata injection.J EthnopharmacolHouttuynia cordata (Saururaceae) injection (HCI) is a traditional Chinese medicine used in China. It was chosen as one of eight types of traditional Chinese medicine that play a unique role in severe acute respiratory syndrome (SARS) owing to the effect of curbing inflammation. In order to validate this plausible anti-inflammatory property, the chemical composition of HCI has been analysed by GC/MS, 22 components were identified, and the inflammation induced by carrageenan in the rat pleurisy model and by xylene in the mice ear edema model was adopted to study the anti-inflammatory activity of HCI. Injection of carrageenan into the pleural cavity elicited an acute inflammatory response characterized by protein rich fluid accumulation and leukocyte infiltration in the pleural cavity. The peak inflammatory response was obtained at 24 h when the fluid volume, protein concentration, C-reactive protein and cell infiltration were maximums. The results showed that these parameters were attenuated by HCI at any dose and touched bottom at dose of 0.54 ml/100 g, although less strong than dexamethasone. This drug was also effective in inhibiting xylene induced ear edema, and the percentage of inhibition came to 50% at dose of 80 microl/20 g. The results clearly indicate that HCI have anti-inflammatory activity.
Suspected simultaneous bilateral anterior ischemic optic neuropathy in a patient with Behçet's disease.Ocul Immunol InflammTo report a 47-year-old Japanese woman with a one-year history of Behçet's disease who complained of sudden bilateral visual loss with concurrent anterior ischemic optic neuropathy (AION).The patient's Snellen visual acuity was 0.1 (OD) and 0.3 (OS) of onset. There was bilateral mild anterior chamber inflammation. Bilateral optic disc pale swelling was observed without retinal exudates and edema. Fluorescein angiography demonstrated bilateral hypofluorescence of the optic disc in early frames but with no distinct retinal vasculitis. Visual field showed bilateral relative central scotoma and right altitudinal hemianopsia. Laboratory examination revealed an ESR of 26 mm in the first hour with a C-reactive protein level of < 0.3 mg/dl. Periocular injection of triamcinolone acetonide in both eyes without systemic corticosteroid administration improved her visual acuity to 0.7 (OD) and 1.2 (OS) within 45 days of onset. Bilateral optic disc swelling gradually resolved. In the early stages, fluorescein angiography demonstrated normal optic disc filling in both eyes. There was a residual right central scotoma on visual field.We observed an extremely rare case of simultaneous bilateral AION with Behçet's disease with marked visual recovery within 45 days of onset.
2006Patterns of pulmonary complications associated with sirolimus.RespirationSirolimus inhibits human fibroblast cell proliferation in cell cultures from transbronchial biopsies of lung transplant recipients. However, a few cases of interstitial pneumonitis and bronchiolitis obliterans organizing pneumonia have been recently described in solid organ transplant recipients, including a fatality in a heart transplant recipient. We studied the patterns of pulmonary adverse effects associated with sirolimus in 4 renal transplant recipients who developed pulmonary opacities on chest radiograph, which were proved to be noninfectious in origin. Lung biopsy was performed to obtain histological diagnosis (3 interstitial pneumonitis, 1 necrotizing vasculitis). Symptoms were dyspnea (4), cough (2), hemoptysis (1), fever (1) and eyelid edema (1). Those with interstitial pneumonitis had bilateral basal opacities on chest X-ray, and histopathology showed mild lymphoplasmocytic interstitial inflammation, scattered intraalveolar epitheloid granulomas and a focal pattern of organizing pneumonia. Serum C-reactive protein (CRP) was elevated and bronchoalveolar lavage revealed lymphocytosis (77, 79.5 and 31%). The fourth patient had an opacity localized in the upper lobe, which progressed to both the lower lobes, and histopathology showed multifocal necroses of lung tissue with lymphoplasmocytic vasculitis and scattered granulomas. In this patient, the serum CRP level was not elevated and bronchoalveolar lavage was normal. Pulmonary symptoms and opacities on chest radiograph resolved and the serum CRP level became normal after sirolimus was stopped in all patients. Sirolimus may be a cause of interstitial pneumonitis or pulmonary vasculitis, and withdrawal of sirolimus is therapeutic.
2005Efficacy and tolerability of combination therapy with valsartan plus hydrochlorothiazide compared with amlodipine monotherapy in hypertensive patients with other cardiovascular risk factors: the VAST study.Clin TherRecent antihypertensive treatment guidelines recommend greater use of combination therapies.The primary objective of this study was to determine whether combination therapy with valsartan 160 mg plus hydrochlorothiazide (HCTZ) 25 mg OD would be more effective than monotherapy with amlodipine 10 mg OD in reducing systolic blood pressure (SBP) in patients with moderate (stage II) hypertension and > or =1 other cardiovascular risk factor or concomitant condition. A secondary objective was to assess the effects of the study treatments on circulating markers of endothelial dysfunction and vascular inflammation.This was a multicenter, randomized, double-blind, active-controlled, 24-week study. After a 2-week, single-blind, placebo run-in period, patients were randomized to 3 groups, 2 of them receiving valsartan 160 mg OD and 1 receiving amlodipine 5 mg OD. At week 4, HCTZ 12.5 mg OD was added to valsartan in one of the treatment groups (V+HCTZ12.5), HCTZ 25 mg OD was added to the other (V+HCTZ25), and the amlodipine dose was force-titrated to 10 mg OD (A10). The primary efficacy variable was change in mean sitting SBP at week 24. Other variables were changes in mean sitting diastolic blood pressure (DBP) and mean pulse pressure (PP) from baseline, and response rate (systolic response defined as mean sitting SBP <140 mm Hg or a reduction in mean sitting SBP of > or =20 mm Hg from baseline; diastolic response defined as mean sitting DBP <90 mm Hg or a reduction in mean sitting DBP of > or =10 mm Hg from baseline). Changes in the following markers of endothelial dysfunction were determined at baseline and weeks 4, 12, and 24 in all randomized patients from the participating European and South African centers: high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), vascular tissue plasminogen activator (t-PA) antigen, and oxidized low-density lipoprotein (LDL).The study enrolled 1088 patients with moderate hypertension (mean age, 61 years; 82% white; 53% women). The intent-to-treat population consisted of 1079 patients: 357 in the V+HCTZ12.5 group, 363 in the V+HCTZ25 group, and 359 in the A10 group. At baseline, the groups were comparable in terms of blood pressure and most other characteristics; the only statistically significant difference between groups was in the proportion of patients aged > or =65 years, which was lower in the amlodipine group (P = 0.01). At the end of the study, the least squares mean (SD) changes from baseline in mean sitting SBP were 27.1 (13.7), 29.7 (13.7), and 27.6 (13.8) mm Hg in the V+HCTZ12.5, V+HCTZ25, and A10 groups, respectively, with corresponding percent changes of 16%, 18%, and 17% (P < 0.05, V+HCTZ25 vs A10). The changes in mean sitting DBP did not differ significantly between groups. The reductions in PP were 17.5 (11.3), 18.7 (11.3), and 16.9 (11.3) mm Hg, with percent changes of 24%, 26%, and 23% (P < 0.05, V+HCTZ25 vs A10). Significant reductions in t-PA antigen were observed in both combination-therapy groups compared with the amlodipine monotherapy group at week 12 (P < 0.05); the reductions remained significant through the end of the study in the V+HCTZ12.5 group. There was a significant reduction in IL-6 and hs-CRP at week 12 with V+HCTZ25 compared with A10 (P < 0.05). Oxidized LDL values were reduced by approximately 10% with all treatments. Rates of total adverse events were significantly lower with the valsartan-based treatments compared with amlodipine monotherapy (49.7%, 49.6%, and 67.5% with V+HCTZ12.5, V+HCTZ25, and A10, respectively; P < 0.05). Rates of total discontinuations were a respective 10.1%, 9.0%, and 24.5%, and discontinuation rates due to AEs were 4.2%, 3.5%, and 18.2%. Leg edema was more common with amlodipine monotherapy than with the valsartan-based combinations (P < 0.05).In this group of patients with moderate hypertension and > or =1 other cardiovascular risk factor or concomitant condition, similar and greater antihypertensive effects were seen with the fixed-dose combinations of valsartan 160 mg and HCTZ 12.5 and 25 mg OD, respectively, compared with amlodipine 10 mg OD, with significantly lower rates of treatment-related adverse events and possible beneficial effects on vascular markers.
2005Metabolic effects of pioglitazone in combination with insulin in patients with type 2 diabetes mellitus whose disease is not adequately controlled with insulin therapy: results of a six-month, randomized, double-blind, prospective, multicenter, parallel-group study.Clin TherType 2 diabetes mellitus (DM) is a progressive disease. Initial therapy begins with dietary and lifestyle modifications. However, as the disease progresses, glycemic control becomes more difficult to attain, often requiring > or =1 oral antihyperglycemic medication (OAM), and finally the addition of insulin to the OAMs and insulin monotherapy.This study was designed to determine the effect of pioglitazone 30 mg plus insulin (PIO + INS) versus placebo plus insulin (PLB + INS) on glycemic control, the serum lipid profile, and selected cardiovascular risk factors in patients with type 2 DM whose disease was inadequately controlled with insulin therapy alone despite efforts to intensify such treatment.This was a 6-month, randomized, double-blind, prospective, multicenter, placebo-controlled, parallel-group study. Patients with type 2 DM and a glycosylated hemoglobin (HbA(1c)) value > or =7.5% who were using insulin (with or without OAMs) entered a 3-month insulin intensification phase to achieve blood glucose targets with insulin monotherapy. After insulin intensification, those patients with HbA(1c) values > or =7.0% were randomized to PIO + INS or PLB + INS. The primary end point was the change in HbA(1c) from baseline. Cardiovascular risk markers (highly sensitive C-reactive protein [hs CRP] and plasminogen activator inhibitor-1 [PAI-1]) were measured at baseline and end point.Of the 289 patients randomized to treatment (mean [SD] age, 58.9 [7.1] years; 164 women, 125 men), 142 received PIO + INS and 147 received PLB + INS. A total of 263 patients completed the study. After 6 months, PIO + INS reduced mean HbA(1c) (-0.69%; P < 0.002) and mean fasting plasma glucose ([FPG] -1.45 mmol/L; P < 0.002) from baseline. PLB + INS produced no significant changes in HbA(1c) or FPG. The between-treatment differences for HbA(1c) (-0.55%; P < 0.002) and FPG (-1.80 mmol/L; P < 0.002) occurred despite a reduction of insulin dose in the PIO + INS group from baseline (-0.16 U/d . kg; P < 0.002). Significant between-group differences were observed for high-density lipoprotein cholesterol (0.13 mM; P < 0.002), triglycerides (ratio of geometric mean [PIO/PLB], 0.871; P < 0.01), atherogenic index of plasma (-0.11; P < 0.002), PAI-1 (-5.10 U/mL; P < 0.001), and hs CRP (-1.47 mg/L; P < 0.05). The rate of clinical and biochemical hypoglycemia (blood glucose <2.8 mmol/L) did not differ statistically between treatment groups, but reported incidences of subjective hypoglycemia occurred more often with PIO + INS than with PLB + INS (90 vs 75; P < 0.05). Edema was more common with PIO + INS than with PLB + INS (20 vs 5 instances, respectively), as was gain (mean [SEM]) in body weight (4.05 [4.03] vs 0.20 [2.92] kg, respectively).Adding pioglitazone to insulin in these study patients with type 2 DM whose disease was inadequately controlled with insulin monotherapy further improved their glycemic control.
2005MRI features of Lyme arthritis in children.AJR Am J RoentgenolOligoarthritis is the most common manifestation of late Lyme disease in children. Considerable overlap can occur in the clinical presentation of Lyme arthritis and acute septic arthritis. Early differentiation is critical, given the disparate therapeutic implications; Lyme arthritis is treated with outpatient oral antibiotics, while septic arthritis requires hospitalization, IV antibiotics, and, often, surgical drainage. We wanted to identify MRI features that may distinguish Lyme arthritis from septic arthritis in children.Knee MR images in 11 children with Lyme arthritis and 7 with septic arthritis, with a mean age 10.6 years old and 11.7 years old, respectively, were reviewed by a radiologist blinded to the final diagnosis. Joint effusion size, synovial thickness, adenopathy, subcutaneous, marrow, and muscle edema on MRI; and clinical parameters including age, sex, fever, WBC, erythrocyte sedimentation rate, C-reactive protein, and joint fluid WBC in the two patient groups were compared using univariate and multivariate analyses.Subcutaneous edema was seen in all septic arthritis patients but in only one of 11 patients with Lyme arthritis (p < 0.01). Myositis and adenopathy were present in all Lyme arthritis patients and two of seven patients with septic arthritis (both p < 0.01). No significant difference was present in synovial thickness, marrow edema, or joint fluid size. There were no statistically significant differences in the clinical parameters assessed.Our results identified three MRI features, specifically, myositis, adenopathy, and lack of subcutaneous edema, that strongly suggest the diagnosis of Lyme arthritis rather than septic arthritis in children with acute inflammation of the knee. Awareness of these characteristic MRI features may avoid unnecessary invasive procedures and cost.
2005[Infectious complications after arthroscopic replacement of the cruciate ligaments].Acta Chir Orthop Traumatol CechInfection following replacement of the cruciate ligaments of the knee joint may result in not only graft failure but also complete destruction of the joint. The aim of this study was to report the authors' experience with the diagnosis and therapy of this, fortunately occasional, complication.In the period from October 1999 till June 2003, a total of 2372 arthroscopic operations of the knee joint were carried out; of these, 908 were cruciate ligament replacements. Three surgeons using the same technique were involved. An autologous graft taken from the ligamentum patellae and fixed with interference screws was used in 857 knees, and a graft derived from the tendon of the semitendinosus or the gracilis muscle, with "endobutton" fixation, was employed. Two kinds of inflammatory complications were recorded in the early post-operative period, i. e., infection of the articular cavity and infected subcutaneous hematoma at site of graft collection.When infection of the articular cavity was suspected because of severe pain, perspiration, motion restriction, articular exudate and increased temperature, arthrocentesis was performed and a sample of the fluid withdrawn was sent for cultivation; laboratory tests (blood counts, erythrocyte sedimentation rate, C-reactive protein) were carried out and antibiotic therapy was started. When there was no subsidence of signs within 24 h, revision surgery was carried out without waiting for the results of laboratory examination. Coagula from inside of the cavity were removed through a short incision on the lateral side of the suprapatellar recess and, after repeated thorough irrigation, a suction drain was inserted. Antibiotic therapy was administered parenterally. Infected subcutaneous hematoma, associated with edema, reddening and tension of the skin, pain, fluctuation and, in some cases, high temperature, was treated by disintegration of the wound, removal of the hematoma, debridement and thorough irrigation. After drain insertion, the wound was closed by suture. The development of infectious complications was assessed in relation to the risk factors described in the literature, namely, patient's age, operating room time and tourniquet application, previous infections of the upper respiratory or urinary tracts, previous surgery on the same joint and the season in which the operation was performed.A total of 37 revision operations following replacement of the cruciate ligaments of the knee joint were carried out; of these, 29 involved the articular cavity. An infectious agent was found in six cases (0.7 % of the total number of cruciate ligament replacements). Eight knees were treated for hematoma in the wound at site of graft collection and, in seven of them, Staphylococcus aureus was isolated (0.8 % of the total number of crucial ligament replacements). For recurrent problems the distal fixation material had to be removed in two patients at 6 and 12 months, respectively. Afterwards the patients were free from symptoms. The only risk factor for the development of infection was found to be previous surgery on the same joint.The authors prefer early revision surgery in the cases showing signs of developing infection in the articular cavity or hematoma in the wound after graft collection. Therefore the results of positive cultivation were fewer in comparison with other relevant reports. In revision surgery on the articular cavity, the authors made a 2-cm incision on the lateral side of the suprapatellar recess, which enabled them to wash out all coagula, in comparison to other authors who recommend irrigation with the use of arthroscopic apparatus only. The early intervention made it possible to keep all grafts in situ. The only factor associated with a higher occurrence of complications in our patients was a previous operation on the same joint.On the basis of their experience with arthroscopic replacement of the cruciate ligaments, the authors recommend an active approach if the development of infectious complications is suspected. In our patients, no persisting sequelae were recorded.
2005Evaluation of antioxidant effect of Semecarpus anacardium Linn. nut extract on the components of immune system in adjuvant arthritis.Vascul PharmacolThe effect of Semecarpus anacardium Linn. nut extract (SA) on the level of Lipid peroxides (LPO) and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) in the lymphocytes and lymphoid organs, namely spleen and thymus of adjuvant induced arthritic rats, were investigated. The results were compared with normal and untreated arthritic rats. The levels of reactive oxygen species (ROS), namely Hydroxy radical, Superoxide radical, and H2O2 were also measured in spleen, thymus, and lymphocytes of control and experimental animals. Biochemical markers of inflammation namely C-reactive protein (CRP) level and Erythrocyte sedimentation rate (ESR) were determined. Anti-arthritic profile was evaluated from the changes in the paw edema and arthritic scores of arthritic and drug-treated rats. A significant increase in the level of LPO, ROS and decreased levels of antioxidant enzymes in arthritic rats were observed. On treatment with the drug, the above changes were reverted back to near normal levels. The increment in CRP level and ESR observed in arthritic animals were found to be significantly restored in SA treated rats. There were no significant changes in sole drug-administered normal rats. Semecarpus anacardium Linn. nut extract significantly decreased the paw edema and arthritic score in arthritic rats on administration, whereas in untreated arthritic rats, there was a significant edema in the hind paw.
2005[Organ changes induced by ergot derivative dopamine agonist drugs: time to change treatment guidelines in Parkinson's disease?].Cas Lek CeskErgot derivative dopamine agonists, e.g. pergolide, bromocriptine, dihydroergocriptine used in treatment of Parkinson's disease can cause pleural, pericardial, retroperitoneal and valvular fibrotic changes. Case No 1: A 56-year-old woman with PD was treated with pergolide 3mg/24h since July 2002. In June 2003, edema of lower extremities was first noticed and echocardiography found a minor mitral regurgitation without any morphological changes of the valve. In January 2004, left- sided cardiac failure rapidly developed and echocardiography revealed multivalvular insufficiency with predominating severe mitral regurgitation. Mitral valve replacement was performed and pergolide was changed to ropinirole. Until now, neither cardiac functions nor motor status are sufficiently compensated. Case No 2: A 66-year-old-man with PD since 1996 was treated with pergolide 3 mg/day since 1999. In the beginning of 2004, leg edema appeared. On examination, bilateral hydronephrosis with ureteric strictures and incipient renal insufficiency was found. Bilateral ureteroplasty was performed and the histology showed periureteric fibrosis. Treatment with steroids was initiated and pergolide was changed to pramipexole. Despite the treatment, the fibrosis progressed, requiring ureteral stenting. Based on the literature review and on our own experience, we propose following guidelines to minimize the risk of complications: A. Not to use EAD as the first-line dopamine agonists. B. Regularly follow all patients treated with EAD, especially monitor the majorsymptoms: dyspnea, cough, fatigue, leg edema (also asymmetric), symptoms of urinary outflow obstruction, cardiac insufficiency, chest pain, heart murmur. An elevated ESR, C-reactive protein or anemia support the diagnosis. C. All symptomatic patients should undergo workup for serosal fibrosis (according to type of complication): chest X-ray or CT scan, spirometry, renal functions, renal ultrasound, CT of retroperitoneum. D. Before the introduction of EAD therapy, examine the renal functions, perform chest X-ray and echocardiography. Screening echocardiography should be performed in 3-6 months and subsequently in every 6-12 months.
2000Gastrointestinal manifestation and outcome of Henoch-Schonlein purpura in children.Chang Gung Med JWe reviewed the clinical and laboratory manifestations and analyzed the outcome in children with Henoch-Schönlein purpura (HSP) and gastrointestinal involvement.The medical records of 158 children who had Henoch-Schönlein purpura with gastrointestinal (GI) involvement admitted to our institution from June 1987 to December 1998 were reviewed. We retrospectively analyzed their demographic features, clinical manifestations, and outcome.Totally 104 boys and 54 girls (male: female = 1.9:1) were enrolled in this study, with a mean age of diagnosis of 5.8+/-4.8 years (range: 2 to 13 years). Sixty-three (40%) of our patients had preceding upper respiratory tract infection. The main GI manifestations included abdominal pain (88%); GI bleeding (75%), and vomiting (25%). Bowel edema was found in 71% of examined patients. Upper GI endoscopy provided supportive evidence of HSP in 58% of patients examined. Five patients were found to have marked jejunal edema with bowel collapse leading to severe intestinal obstruction. Thirteen patients (8.2%) had emergent complications including massive blood loss from GI tract in 4, seizure in 2, severe hypoalbuminemia in 2, and emergent surgical condition in 6. Twenty-one patients (13%) experienced prolonged hospitalization (> or =10 days). Bilious vomiting, hematemesis, leukocytosis (>20000/cmm), high C-reactive protein (>50 mg/l), and hemorrhagic erosive duodenitis were found to correlate with prolonged hospitalization. Fourteen (20%) of 70 patients who received follow-up for more than 5 years experienced GI recurrence of HSP.Despite severe and protracted GI symptoms in some HSP patients, the overall prognosis of GI involvement in children with HSP remains good.
2004Trace microalbuminuria in inflammatory cystoid macular edema.Am J OphthalmolTo assess the role of cardiovascular morbidity, its risk factors, and microalbuminuria in the development of inflammatory cystoid macular edema (CME).A matched case-control study.study population: We included 24 consecutive patients with uveitis and CME. Twenty four uveitis patients without CME, matched for age and duration of uveitis served as controls. intervention and observation procedures: Patients and controls were interviewed for the presence of cardiovascular risk factors and cardiovascular morbidity. All medications were registered. Morning urinary albumin concentration was measured, as well as blood pressure, C-reactive protein, and creatinine in blood. Patients suffering from diabetes mellitus were excluded from this study. main outcome measures: The presence of cardiovascular morbidity and its risk factors and microalbuminuria in uveitis patients with and without CME.We found a positive association between trace- and/or microalbuminuria and inflammatory CME (P = .001; odds ratio 13.0, 95% CI 2.5 to 68.1 and P = .015; odds ratio 5.9, 95% CI 1.6 to 22.6), but no relation between CME and cardiovascular morbidity or its risk factors. No additional association between trace- and/or any microalbuminuria and general characteristics of patients, specific factors related to general disease as a cause of ocular inflammation, location of uveitis, duration of uveitis, and medication was found.The presence of trace- and/or microalbuminuria in inflammatory CME might indicate the presence of early systemic vascular disease and carry the risk of developing CME. This finding brings new insight into the pathogenesis of CME and could open up new avenues for the treatment of CME.
2004Resting energy expenditure and subsequent mortality risk in peritoneal dialysis patients.J Am Soc NephrolCardiovascular disease is the leading cause of death in ESRD patients and is strongly associated with malnutrition. The mechanism of malnutrition is not clear, but hypermetabolism is suggested to contribute to cardiac cachexia. This study examined resting energy expenditure (REE) in relation to the clinical outcomes of ESRD patients who receive continuous ambulatory peritoneal dialysis (CAPD) treatment. A prospective observational cohort study was performed in 251 CAPD patients. REE was measured at study baseline using indirect calorimetry together with other clinical, nutritional, and dialysis parameters. Patients were followed up for a mean +/- SD duration of 28.7 +/- 14.3 mo. REE was 39.1 +/- 9.6 and 40.1 +/- 9.0 kcal/kg fat-free edema-free body mass per day for men and women, respectively (P = 0.391). Using multiple regression analysis, fat-free edema-free body mass-adjusted REE was negatively associated with residual GFR (P < 0.001) and serum albumin (P = 0.046) and positively associated with diabetes (P = 0.002), cardiovascular disease (P = 0.009), and C-reactive protein (P = 0.009). At 2 yr, the overall survival was 63.3, 73.6, and 95.9% (P < 0.0001), and cardiovascular event-free survival was 72.3, 84.6, and 97.2% (P = 0.0003), respectively, for patients in the upper, middle, and lower tertiles of REE. Adjusting for age, gender, diabetes, and cardiovascular disease, patients in the upper and middle tertiles showed a 4.19-fold (95% confidence interval, 2.15 to 8.16; P < 0.001) and a 2.90-fold (95% confidence interval, 1.49, 5.63; P = 0.002) respective increase in the risk of all-cause mortality compared with those in the lower tertile. However, the significance of REE in predicting mortality was gradually reduced when additional adjustment was made for C-reactive protein, serum albumin, and residual GFR in a stepwise manner. In conclusion, a higher REE is associated with increased mortality and cardiovascular death in CAPD patients and is partly related to its close correlations with residual kidney function, cardiovascular disease, inflammation, and malnutrition in these patients.
2004Targeted inhibition of gene expression of pancreatitis-associated proteins exacerbates the severity of acute pancreatitis in rats.Scand J GastroenterolPancreatitis-associated protein (PAP) is a secretory protein not normally expressed in healthy pancreas but highly induced during acute pancreatitis. While PAP has been shown to be anti-bacterial and anti-apoptotic in vitro, its definitive biological function in vivo is not clear.To elucidate the function of PAP, antisense oligodeoxyribonucleotides (AS-PAP) targeting all three isoforms of PAP were administered via intrapancreatic injections (5 mg kg day, 2 days) to rats prior to induction of pancreatitis.Severity of pancreatitis and cytokine gene expression in peripheral blood mononuclear cells (PBMC) were evaluated. Administration of AS-PAP, but not the scrambled oligodeoxyribonucleotide (SC-PAP) control, reduced pancreatitis-induced PAP expression by 55.2 +/- 6.4%, 44.0 +/- 8.9%, and 38.9 +/- 10.7% for PAP isoforms I, II, and III, respectively, compared to saline-treated controls (P < 0.05 for all). Inhibition of PAP expression significantly worsened pancreatitis: serum amylase activity, pancreas wet weight (reflecting edema), and serum C-reactive protein levels all increased in AS-PAP-treated animals compared to SC-PAP-treated controls (by 3.5-, 1.7-, and 1.7-fold, respectively; P < 0.05 for all). Histopathologic evaluation of pancreas revealed worsened edema, elevated leukocyte infiltration, and fat necrosis after AS-PAP treatment. Gene expressions of IL-1 microm and IL-4 were significantly higher in PBMC isolated from AS-PAP-treated rats compared to SC-PAP controls.This is the first in vivo evidence indicating that PAP mediates significant protection against pancreatic injury. Our data suggest that PAP may exert its protective function by suppressing local pancreatic as well as systemic inflammation during acute pancreatitis.
2004Severe ulcerative colitis: prospective study of parameters determining outcome.J Gastroenterol HepatolOne-third of patients with exacerbations of ulcerative colitis (UC) require colectomy and 1% die. Although several studies have reported parameters associated with failure of medical treatment, studies using multivariate analysis of various predictors are scanty.Demographic, clinical and laboratory parameters within 48 h of admission of 50 consecutive patients (55 episodes) were prospectively recorded. Each episode was treated with intravenous hydrocortisone, antibiotics and fluid administration. The data of patients who failed to respond, deteriorated, developed complications requiring emergency surgery or died within 7 days of hospitalization, were compared with the data of those who responded during this period using Mann-Whitney U-test or chi-squared tests. Variables found to be significant on univariate analysis were entered into a multivariate model.Medical treatment failed in 10 of 55 episodes; eight had surgery (one died), another died with bowel perforation and peritonitis and one left hospital in a moribund state. Younger age, pedal edema, transverse colonic diameter >5 cm on abdominal radiograph, low hemoglobin, low serum albumin, high C-reactive protein, presence of fibrin degradation product (FDP) in serum, low serum fibrinogen, prolonged prothrombin time, Truelove-Witt's fulminant disease, and high clinical activity index were associated with failure of medical treatment on univariate analysis. All the above variables were significant by multivariate analysis except age, serum albumin level and presence of FDP.It may be possible to predict the failure of medical treatment in exacerbations of UC using a scoring system based on clinical parameters and simple laboratory tests.
2004Approach to the management of diabetic patients with heart failure: role of thiazolidinediones.Am Heart JDiabetes mellitus is a chronic, progressive disease that results in microvascular and macrovascular complications. Patients with diabetes are at high risk for developing heart failure, and the prevalence of diabetes in patients with heart failure ranges from 24% to 44%, with an estimated 1 to 2 million individuals in the United States having both diabetes and heart failure. Patients with diabetes and heart failure are at increased risk for mortality. Primary treatment goals in diabetes include restoration and maintenance of normoglycemia, avoidance of diabetic complications, and prevention of cardiovascular events. The range of therapeutic options for glycemic control has been extended with the introduction of thiazolidinediones (TZDs) used as monotherapy or in combination with other oral antidiabetic medications or insulin. TZDs decrease plasma insulin levels, improve endothelial function, decrease vascular inflammation, and decrease C-reactive protein levels, effects that are potentially beneficial in patients with heart failure. Weight gain and peripheral edema are recognized side effects of these drugs, particularly when used in combination with insulin. Although health care providers should be aware of the potential risk of worsened heart failure when TZDs are used in patients with diabetes and heart failure, these agents may be considered for use in patients with New York Heart Association class I and II heart failure when appropriate monitoring can be provided. Prospective clinical trials are currently under way to further define the cardiovascular safety and efficacy of TZDs in diabetic patients with heart failure.
Klinefelter's syndrome presenting with leg ulcers.SkinmedA 54-year-old man of Persian origin presented to our department with a 1-year history of ulcers on the right leg that had been unresponsive to numerous topical treatments, accompanied by lymphedema of the right leg. Medical history included hypergonadotropic hypogonadism, which had not been further investigated. He was treated for 20 years with testosterone IM once monthly, which he stopped a year before the current hospitalization for unclear reasons. The patient reported no congenital lymphedema. Physical examination revealed two deep skin ulcers (Figure 1) on the right leg measuring 10 cm in diameter with raised irregular inflammatory borders and a boggy, necrotic base discharging a purulent hemorrhagic exudate. Bilateral leg pitting edema and right lymphangitis with lymphadenitis were noted. He had low head hair implantment, sparse hair on the body and head, hyperpigmentation on both legs, onychodystrophia of the toenails (mainly the large toe and less prominent on the other toes), which was atrophic lichen-planus-like in appearance and needed no trimming (Figure 2), normal hand nails, oral thrush, and angular cheilitis. Other physical findings were gynecomastia, pectus excavatum, small and firm testicles, long extremities, asymmetrical goiter, systolic murmur 2/6 in left sternal border, and slow and inappropriate behavior. The patient's temperature on admission was 39 degrees C. Blood cultures were negative for bacterial growth. Results of laboratory investigations included hemoglobin (11.2 g/dL), hematocrit (26.8%), normal mean corpuscular volume and mean corpuscular hemoglobin volume, and red blood cell distribution width (16%). Blood smear showed spherocytes, slight hypochromia, anisocytosis, macrocytosis, and microcytosis. Blood chemistry values were taken for iron (4 micro g/dL [normal range 40-150 micro g/dL]), transferrin (193 mg/dL [normal range 220-400 mg/dL]), ferritin (1128 ng/mL [normal range 14-160 ng/mL]), transferrin saturation (1.5% [normal range 20%-55%]), serum folate (within normal limits), and vitamin B12 (within normal limits). Direct Coombs' test equaled positive 2 + IgG. All these values indicated anemia of chronic diseases combined with hemolytic anemia. Further blood work-up tested antinuclear antibody (positive <1:80 homogeneous pattern), rheumatoid factors (143 IU/mL [positive >8.5 IU/mL]), C-reactive protein (286 mg/L [normal range 0-5 mg/L]), anticardiolipin IgM antibody (9.0 monophosphoryl lipid U/mL [normal range 0-7.00 MPL U/mL]) and antithrombin III activity (135% [normal range 74%-114%]). Results of other blood tests were within normal limits or negative, including lupus anticoagulant, beta2 glycoprotein, anticardiolipin IgG Ab, anti-ss DNA Ab, C3, C4, anti-RO, anti-LA, anti-SC-70, anti-SM Ab, P-ANCA, C-ANCA, TSH, FT4, anti-T microsomal, antithyroglobulin, protein C activity, protein S free, cryoglobulins, serum immunoelectrophoresis, VDRL, hepatitis C antibodies, hepatitis B antigen, and human immunodeficiency virus. Endocrinological work-up examined luteinizing hormone (22.9 mIU/mL [normal range for adult men 0.8-6 mIU/mL]), follicle stimulating hormone (49.7 mIU/mL [normal range for adult men 1-11 mIU/mL]), testosterone (0.24 ng/mL [normal range for adult men 2.5-8.0 ng/mL]), bioavailable testosterone (0.02 ng/mL [normal range for adult men >0.6 ng/mL]), and percent bioavailable test (8.1% [normal value >20%]). These results indicate hypergonadotropic hypogonadism. Plasminogen activator inhibitor 1 was 6 U (normal value 5-20 U/mL). Karyotyping performed by G-banding technique revealed a 47 XXY karyotype, which is diagnostic of Klinefelter's syndrome. Doppler ultrasound of the leg ulcers disclosed partial thrombus in the distal right femoral vein. X-rays and bone scan displayed osteomyelitis along the right tibia. Histological examination of a 4-mm punch biopsy from the ulcer border revealed hyperkeratosis, acanthosis, hypergranulosis, and mixed inflammatory infiltrate containing eosinophils compatible with chronic ulcer. Multiple vessels were seen, compatible with a healing process. Direct immunofluorescence of the biopsy revealed granular IgM in the dermo-epidermal junction. Indirect immunofluorescence was negative. Thyroid function tests showed normal thyroid stimulating hormone and free throxine4. Multinodular goiter was seen on thyroid scan and ultrasound. Thyroid fine needle aspiration was compatible with multinodular goiter (normal follicular cells, free colloid, macrophages with pigment). IV treatment with amoxicillin-clavulanic acid 1 g t.i.d. was administered for 2 weeks, with a decrease in temperature and normalization of the leukocyte level. Oral antibiotic treatment with amoxicillin-clavulanic acid was continued for 10 more days, followed by 25 days of ciprofloxacin for the osteomyelitis. Local treatment included saline soakings followed by application of Promogran (Johnson & Johnson, New Brunswick, NJ) and Kaltostat (ConvaTec Ltd., a Bristol-Myers Squibb Company, New York, NY) with slight improvement. At the same time, the patient was treated with warfarin sodium due to deep vein thrombosis under international normalized ratio 2-3. The patient was treated with IM testosterone once monthly for 1 year, which resulted in a reduction in the diameter and depth of the leg ulcers (Figure 3). Blood tests were not performed for follow-up of the immune state.
[Reiter's syndrome after Salmonella infection].Srp Arh Celok LekTwo patients with Reiter's syndrome, after Salmonella infection were treated on the Infections disease ward at Clinical hospital center in Kragujevac. In the first patient, ten days after the onset of Salmonella infection, signs of edema and pain in the right ankle occurred, accompanied by expressed conjunctivitis. Within next two months consecutive metatarsophalanges changes joint of the right foot have appeared. In the second patient, two weeks after the onset of Salmonella infection, edema of the left hand joints and a week later edema of the right hand and right ankle joints appeared. In both patients inflammatory syndrome was expressed (high erythrocyte sedimentation rates, fibrinogen, C-reactive protein) along with negative rheumatoid factors and positive antigen HLA-B27. Outcome of the disease in both cases was favourable upon receiving nonsteroid antirheumatic therapy. Signs of arthritis disappeared after three months. No signs of recurrent arthritis have been seen during the next four years in the first and next two years in the second patient.
2004[Relapsing polychondritis with an intracranial granuloma: a case report].Rinsho ShinkeigakuWe report a case of relapsing polychondritis (RP) with an intracranial granuloma. A 67-year-old man developed progressive disorientation during the course of RP with left auricular chondritis and episcleritis. He had history of sinusitis and rupture of an aneurysm in middle cerebral artery. Laboratory examinations revealed high erythrocyte sedimentation rate and positive C-reactive protein. Head CT and MRI with contrast enhancement showed a mass adjacent to the falx cerebri and lesions in the frontal skull base. The mass was surrounded by extensive perifocal edema that spread mainly into the frontal white matter on both sides. Histologically, the mass displayed an inflammatory granuloma. By removal of the mass, edema decreased around the granuloma, and his disorientation improved markedly. Surgical findings revealed the granuloma was separated from sinusitis. There are a few reports on RP with an intracranial granuloma.
2004Magnetic resonance imaging of wrist and finger joints in healthy subjects occasionally shows changes resembling erosions and synovitis as seen in rheumatoid arthritis.Arthritis RheumTo explore the presence of changes resembling rheumatoid arthritis erosions and synovitis in metacarpophalangeal (MCP) and wrist joints of healthy individuals on magnetic resonance imaging (MRI) and to compare the MRI findings with conventional radiographic, clinical, and biochemical findings.Twenty-eight healthy individuals were studied. Contrast-enhanced MRI and conventional radiography of the dominant wrist and second through fifth MCP joints were performed, coupled with standard clinical assessments and biochemical analyses. MR images were evaluated according to the latest OMERACT (Outcome Measures in Rheumatology Clinical Trials) recommendations with respect to synovitis, erosions, and bone marrow edema.Conventional radiography revealed erosion-like changes in 1 of 224 MCP joint bones (0.4%) and in 1 of 420 wrist joint bones (0.2%). MRI depicted low-grade erosion-like changes in 5 of 224 MCP joint bones (2.2%) and in 7 of 420 wrist joint bones (1.7%), but postcontrast enhancement within the lesion was detected in only 8.3% of these. MRI depicted low-grade synovitis-like changes in 10 of 112 MCP joints (8.9%) and in 8 of 84 assessed wrist areas (9.5%), while only minimal early synovial enhancement was detected by dynamic MRI. Three subjects had elevated serum levels of C-reactive protein, and these subjects displayed 44.5% of the synovitis-like changes and 41.7% of the erosion-like changes. Bone marrow edema-like changes were not found in any joints.Changes resembling mild synovitis or small bone erosions are occasionally found in the MCP and wrist joints of healthy controls. Signs of synovitis on dynamic MRI, enhancement within bone erosion-like changes, and signs of bone marrow edema appear rarely or are absent in healthy controls. These signs may thus prove to be very specific in the distinction between arthritic and normal joints.
2004Sacroiliitis in patients with ankylosing spondylitis: association of MR findings with disease activity.Magn Reson ImagingThe purpose of this study was to determine whether MR findings can correlate disease activity as measured by laboratory markers in ankylosing spondylitis. MR images in 19 patients with ankylosing spondylitis were retrospectively analyzed for cartilage abnormality, periarticular erosion, synovial enhancement, and bone marrow edema. Each MR finding was correlated with laboratory inflammatory markers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) and the sum of ESR + CRP. Synovial enhancement showed a significant correlation with ESR (r=0.58; p<0.01) and increased activity at bone scan (r=0.74; p<0.005), whereas there was no significant correlation with CRP. A significant correlation was found between ESR + CRP and synovial enhancement (r=0.54; p<0.05). Synovial enhancement was more common when ESR + CRP was greater than 30 (p<0.05). In conclusion, synovial enhancement at MR imaging could correlate disease activity as measured by laboratory inflammatory markers in ankylosing spondylitis.
2004C-reactive protein in early prediction of pancreatic necrosis.Medicina (Kaunas)to determine relation between the C-reactive protein and pancreatic necrosis, and to estimate the prognostic value of C-reactive protein in early diagnosis of pancreatic necrosis.During 2001, 78 patients with acute pancreatitis were included in the study. The clinical data, diagnostic procedures, and laboratory values were analyzed. According to severity of the disease patients were divided into two groups. Group I consisted of 17 patients with necrotic pancreatitis, group II--of 61 patients with pancreatic edema. Contrast-enhanced computed tomography scan was used to diagnose pancreatic necrosis with subsequent fine-needle aspiration for microbiological evaluation. C-reactive protein concentration in serum was measured on day 1, 2, 3, 5, 7 and 9 after admission. The sensitivity, specificity, positive and negative predictive values for different C-reactive protein concentration cut-off (100-150 mg/l) were calculated. Average C-reactive protein values were compared between groups by t test for unpaired data. The difference was assumed statistically significant when p<0.05.There was no significant difference in demographic data between the groups. Necrosis of the pancreas was demonstrated on computed tomography scan in 17 cases. The highest C-reactive protein values were detected on day 3 in group I patients. The difference of average C-reactive protein concentration was significant between groups on all days except day 7. The highest sensitivity and negative predictive value (94.1% and 95.7% respectively) was obtained for C-reactive protein cut-off at 110 mg/l.The results of our study show the C-reactive protein values increase significantly in early stages of necrotic pancreatitis. C-reactive protein is an important prognostic marker of pancreatic necrosis with the highest sensitivity and negative prognostic value given the cut-off is 110 mg/l. The patients with C-reactive protein below 110 mg/l are low risk to develop pancreatic necrosis.
2003Portal vein thrombosis after splenectomy for gastric malignant lymphoma.Gastric CancerPortal vein thrombosis (PVT) has rarely been documented in patients after splenectomy for gastric malignancy. We report a case of PVT that occurred after splenectomy as part of an en-bloc node dissection performed to treat gastric malignant lymphoma. A 38-year-old man underwent total gastrectomy and splenectomy with en-bloc D2 lymph node dissection. The spleen weighed 480 g. On postoperative day (POD) 31, the patient complained of abdominal pain in the right upper quadrant accompanied by fever. Moderate elevations of C-reactive protein (CRP), aspartate transaminase (AST), and alanine transaminase (ALT) were noted. Contrast-enhanced computed tomography (CT) and ultrasonography disclosed thrombus in the portal vein and the splenic vein. There were no abnormalities in the levels of lupus anticoagulant, protein C antigen, protein S antigen, or antithrombin III (AT III). A diagnosis of PVT was made, and prompt treatment, including intravenous heparin combined with tissue plasminogen activator (tPA) was initiated, followed by longterm warfarin. This treatment resulted in clinical improvement, but failed to achieve thrombolysis in the portal vein. At follow-up after 6 months, the patient complained of postprandial abdominal pain with persistent peripheral edema and ascites. This case indicates that splenectomy for en-bloc node dissection in gastric malignancy is a possible cause of PVT. Because both the symptoms and the laboratory data in PVT are nonspecific, a high level of clinical suspicion and a low threshold for obtaining imaging examinations are important in the early diagnosis of PVT. Surgeons should remember PVT among several other complications whenever patients treated with radical gastrectomies are symptomatic and imaging studies are considered necessary.
2004Pathophysiological significance of peroxidative stress, neuronal damage, and membrane permeability in acute mountain sickness.J Appl Physiol (1985)Free radical-mediated changes in vascular permeability and subsequent inflammatory response may be a contributory pathogenetic cofactor responsible for the development of neurological sequelae associated with acute mountain sickness (AMS). To investigate this, 49 subjects were examined at sea level and serially after rapid ascent to 4,559 m. Although the venous concentration of total creatine phosphokinase activity was measured in all subjects, a complementary examination of lipid peroxidation (F(2)-isoprostanes), inflammatory (TNF-alpha, IL-1beta, IL-2, IL-6, IL-8, C-reactive protein), and cerebrovascular tissue damage (neuron-specific enolase) biomarkers was confined to a subcohort of 24 subjects. A selective increase (P < 0.05) in total creatine phosphokinase was observed in subjects diagnosed with AMS at high altitude (n = 25) compared with apparently healthy controls (n = 24). However, despite a marked increase in IL-6 and C-reactive protein attributable primarily to subjects developing high-altitude pulmonary edema, subcohort analyses demonstrated no selective differences in F(2)-isoprostanes, neuron-specific enolase, or remaining proinflammatory cytokines due to AMS (n = 14). The present findings are the first to demonstrate that free radical-mediated neuronal damage of sufficient degree to be detected in the peripheral circulation does not occur and is, therefore, unlikely to be an important, initiating event that is critical for the development of AMS. The pathophysiological significance of increased sarcolemmal membrane permeability and inflammatory response, either as a cause or epiphenomenon of AMS and/or high-altitude pulmonary edema, remains to be elucidated.
2003Type 2 diabetes, cardiovascular risk, and the link to insulin resistance.Clin TherPatients with type 2 diabetes mellitus frequently have coexistent dyslipidemia, hypertension, and obesity, and are at risk for microvascular and macrovascular disease complications such as myocardial infarction, stroke, retinopathy, and microalbuminuria. To optimize cardiovascular health outcomes for patients with type 2 diabetes, strategies to reduce the risks of microvascular and macrovascular disease are needed in clinical practice.This article provides an overview of the cardiovascular risk profile of patients with type 2 diabetes and discusses the cardiovascular consequences of use of the thiazolidinediones (insulin-sensitizing agents) in the treatment of type 2 diabetes.A literature search of MEDLINE/PubMed was performed to identify relevant articles published from 1966 to April 2003. Search terms used were diabetes, cardiovascular disease, atherosclerosis, dyslipidemia, obesity, hypertension, blood pressure, hyperglycemia, inflammation, C-reactive protein, fibrinolysis, plasminogen activator inhibitor type-1, microalbuminuria, thiazolidinediones, safety, hepatotoxicity, and edema. Bibliographies within the identified articles were also evaluated for additional relevant articles and information.Recommendations for cardiovascular risk reduction through preventive and therapeutic strategies that target the symptoms of insulin resistance may reduce the microvascular and macrovascular sequelae of diabetes and ameliorate the impact of other components of the metabolic syndrome, including hypertension, hyperglycemia, and obesity. In this regard, thiazolidinediones are promising therapies.Early data suggest that, in addition to reducing hyperglycemia, pioglitazone and rosiglitazone effect changes in the dyslipidemic profile, hemodynamics, vascular inflammation, and endothelial functioning of patients with type 2 diabetes. Additional research is needed to further distinguish the cardiovascular benefits of these drugs.
2003Anti-glomerular basement membrane antibody-induced glomerulonephritis with periglomerular granulomatous reaction and massive renal eosinophilic infiltration.Am J Kidney DisWe present a case of a 68-year-old man with anti-glomerular basement membrane (anti-GBM) antibody-induced glomerulonephritis accompanied by periglomerular granulomatous reaction and massive eosinophilic infiltration. Periglomerular granulomatous giant cells were derived from macrophages, shown by positive staining for monoclonal antibody against cluster of differentiation 68. Staining for eosinophil cationic protein indicated that activated eosinophils were involved in the tubulitis, as well as in the glomerular injury. The patient was admitted to the hospital with fever, loss of appetite, edema of the extremities, abnormal urinalysis results, and rapid progressive renal failure. At an examination 8 months before admission, his serum creatinine level (1.0 mg/dL [88.4 micromol/L]) and urinalysis results were normal. On admission, an elevated serum creatinine level (5.1 mg/dL [450.8 micromol/L]) and marked eosinophilia (eosinophils, 5.00 x 10(3)/microL [5.00 x 10(9)/L]; 37.2% of total white blood cell count) were observed. Serum anti-GBM antibody titer was high (43 EU), measured by means of an enzyme-linked immunosorbent assay. No respiratory or ophthalmological abnormalities were seen. Intravenous steroid pulse therapy followed by oral prednisolone (PSL) was effective for reducing the fever, eosinophilia, anti-GBM antibody titer, and C-reactive protein level, but did not improve renal function because renal tissue already was irreversibly damaged. Oral PSL dose was tapered off without relapse. The patient underwent long-term hemodialysis therapy, which dissipated the edema. He was discharged from our hospital 65 days after admission. Three months later, his anti-GBM antibody level was less than 10 EU, and the number of peripheral eosinophils stayed with the normal range.
2003Bone edema scored on magnetic resonance imaging scans of the dominant carpus at presentation predicts radiographic joint damage of the hands and feet six years later in patients with rheumatoid arthritis.Arthritis RheumMagnetic resonance imaging (MRI) is capable of revealing synovitis and tendinitis in early rheumatoid arthritis (RA), as well as bone edema and erosion. These features are visible before radiographic joint damage occurs. We sought to examine whether MRI of one body region (the wrist) can be used to predict whole-body radiography scores reflecting joint damage at 6 years.We conducted a 6-year prospective study of a cohort of patients who fulfilled the criteria for RA at presentation, using clinical parameters, radiographs, and MRI scans of the dominant wrist. Of the 42 patients enrolled at baseline, full MRI, radiographic, and clinical data were available for 31 at 6-year followup. MRI scans were scored by 2 radiologists, using a validated scoring system. Radiographs of the hands and feet were graded using the modified Sharp scoring method. MRI and radiography scores obtained at baseline and 6 years were compared, and baseline MRI scores were examined for their ability to predict radiographic outcome at 6 years.At 6 years, the total Sharp score correlated significantly with the total MRI score and the MRI erosion score (r = 0.81, P < 0.0001 and r = 0.79, P < 0.0001, respectively). The 6-year Sharp score also correlated with the baseline total MRI and MRI erosion scores (r = 0.56, P < 0.0001 and r = 0.33, P = 0.03, respectively). MRI synovitis and bone edema scores remained constant for the group as a whole over 6 years, but bone erosion scores progressed (P = 0.0001), consistent with radiographic deterioration. Erosions on 6-year MRI scans were frequently preceded by MRI bone edema at baseline (odds ratio 6.5, 95% confidence interval 2.78-18.1). Regression models indicated that the baseline MRI bone edema score was predictive of the 6-year total Sharp score (P = 0.01), as was the C-reactive protein (CRP) level (P = 0.0002). Neither shared epitope status nor swollen or tender joint counts predicted radiographic outcome in this cohort. A model incorporating baseline MRI scores for erosion, bone edema, synovitis, and tendinitis plus the CRP level and the erythrocyte sedimentation rate explained 59% of the variance in the 6-year total Sharp score (R(2) = 0.59, adjusted R(2) = 0.44).MRI scans performed at the first presentation of RA can be used to help predict future radiographic damage, allowing disease-modifying therapy to be targeted to patients with aggressive disease.
2003[A case with myositis as a manifestation of chronic graft-versus-host-disease (GVHD) with severe muscle swelling developed after aggressive muscular exercise].Rinsho ShinkeigakuWe report a 21-year-old-man, with myositis as a manifestation of chronic graft-versus-host-disease (GVHD). He was diagnosed as having acute myelogenous leukemia at the age of 18 years, and had bone marrow transplantation (BMT) two years after the onset of the disease. Cutaneous manifestation of acute GVHD appeared on the twelfth day following BMT, which responded to prednisolone. Thereafter, GVHD has been well-controlled except for mild liver dysfunction which was thought to be a sign of chronic GVHD. Eleven months after BMT, he enjoyed snowboarding for two days from morning till night. Two days later, he experienced muscle swelling with pain and fever, which gradually worsened for which he was admitted to our hospital. Neurological examination revealed severe proximal and distal muscle swelling with fever and tenderness in all extremities. Mild, symmetrical, proximal weakness was observed in all four limbs. Severity of muscle swelling and its generalized nature restricted the movements of shoulder-, elbow- and ankle-joints and he was unable to walk. Laboratory investigations revealed creatine kinase (CK) of 7,860 IU/L, C-reactive protein (CRP) of 21.5 mg/dL and raised biliary enzymes. MRI generated high intensity signals from the swollen muscles. Muscle biopsy examination of involved areas showed severe interstitial edema and mononuclear cells infiltration. Macrophages were scattered through out the perimysium and endomysium. On the other hand, T cells and B cells were localized to the endomysium. Although a lot of CD8 positive T cells were seen adjacent to non-necrotic fibers, none of them was obviously invading the non-necrotic fibers. Perifascicular atrophy was not seen. Symptoms gradually worsened over two weeks or so when prednisolone was started to which he responded rapidly. While tapering steroids, the symptoms relapsed on resuming aggressive exercise. Resumption of the treatment regime promptly controlled the symptoms. The cause of myositis as a manifestation of chronic GVHD is unclear. T-cell or B-cell dysfunction, collagen-vascular-like processes, viral infection and direct damage by radiation or chemotherapy have been supposed to involve in the disease process. Our case suggests that aggressive muscular exercise could play as a initiator of myositis as a manifestation of chronic GVHD.
2003Carotid plaque inflammation in a patient with unstable angina.Ital Heart JCoronary instability has been associated with multifocal plaque activation in the coronary circulation and in remote vascular districts, suggesting a systemic cause of instability, possibly inflammation. Magnetic resonance imaging offers a great potential for the detection of plaque inflammation. We describe the case of a 73-year-old female admitted for unstable angina, elevated levels of C-reactive protein and three-vessel disease, in whom carotid ultrasound examination revealed an atherosclerotic plaque of the left proximal internal carotid artery with an irregular profile and a heterogeneous echographic texture, determining a 50% stenosis. Magnetic resonance imaging of the plaque before and after contrast enhancement by gadolinium-DTPA showed the following signs of inflammation: an increased vessel wall thickness, an increased triple inversion recovery-fast spin-echo signal intensity indicative of tissue edema, and a homogeneous plaque contrast enhancement indicative of an increased capillary permeability and neovasculature. As the carotid stenosis was < 70% and did not give rise to any symptom, the patient was submitted to coronary bypass surgery without concomitant carotid endarterectomy. Two days later she developed an ischemic stroke with right brachiocrural hemiplegia. In the present case report, the simultaneous presence of coronary instability and a carotid plaque with magnetic resonance features suggestive of inflammation, which was probably responsible for the stroke complicating cardiac surgery, may indicate a multifocal plaque instability.
2003Cases from the Osler Medical Service at Johns Hopkins University. Antiglomerular basement membrane disease.Am J MedA 47-year-old Taiwanese man with no notable medical history was admitted with low-grade fevers and night sweats that had persisted for 5 to 6 weeks. An extensive investigation at another hospital could not determine the cause of the fevers, but documented acute renal failure with a blood urea nitrogen level of 60 mg/dL and a serum creatinine level of 5.6 mg/dL. He was admitted to the Johns Hopkins Hospital for further evaluation.The patient, who had been living in the United States for the past 20 years, reported no recent travel and no behaviors that are associated with transmission of human immunodeficiency virus. He was not taking any medications, and he denied using herbal or nutritional supplements. He had no recent weight loss. There were no specific complaints on review of systems. On physical examination, he was a thin, middle-aged man in no distress. Vital signs included a temperature of 37.5 degrees C, a blood pressure of 166/86 mm Hg, a pulse of 70 beats per minute, a respiratory rate of 16 breaths per minute, and 99% oxygen saturation on room air. Sclera were anicteric, and he had no palpable adenopathy. His lungs were clear, and his heart rate was regular without extra sounds. His abdomen was thin, nontender, and without masses or organomegaly. There was no edema or signs of embolism in the extremities. Laboratory studies revealed a white blood cell count of 14,200/mL(3), a hematocrit of 23.1%, and a platelet count of 456,000/mL(3). Blood chemistries were notable for a blood urea nitrogen level of 61 mg/dL and a serum creatinine level of 7.6 mg/dL. Levels of aminotransferases, total bilirubin, and alkaline phosphatase were within normal limits. Urinalysis revealed large hemoglobin, 1+ protein, numerous red blood cells, and 3 to 5 white blood cells. Numerous red blood cell casts were seen on microscopic examination of the urine sediment. The patient's erythrocyte sedimentation rate was >130 mm/h, and his C-reactive protein level was elevated at 12.6 mg/dL. Serologies were negative for antinuclear antibodies and antineutrophil cytoplasmic antibodies; serum complement levels were normal. What is the diagnosis?
2003Adaptive and inflammatory immune responses in patients infected with strains of Vibrio parahaemolyticus.J Infect DisIn patients with diarrhea caused by Vibrio parahaemolyticus, antibody-secreting cell responses to thermostable direct hemolysin (TDH), lipopolysaccharide (LPS), and whole-cell bacteria were seen. TDH- and LPS-specific responses were seen in serum samples, and immunoglobulin A antibody responses were observed in stool. Levels of C-reactive protein and nitric oxide metabolites increased in the systemic circulation at the onset of illness. Tumor necrosis factor-alpha and lactoferrin levels were high during the acute stage in mucosal secretions and in plasma, whereas interleukin-1beta levels were high only in mucosal secretions. Duodenal and rectal biopsy specimens obtained at the onset of illness showed an acute inflammatory response. The lamina propria showed edema, congestion of blood vessels, and hemorrhage, with an increase in levels of polymorphonuclear neutrophils and macrophages. Strains belonging to different serotypes exhibited varying resistance to killing by serum; the O8:K21 strain was most sensitive. Infection with V. parahaemolyticus results in B cell responses and an acute inflammatory response that is self-limiting.
2002[A case of neurogenic pulmonary edema associated with epileptic seizure].Nihon Kokyuki Gakkai ZasshiWe report a case of neurogenic pulmonary edema associated with epileptic seizure. A 36-year-old woman had had several episodes of fainting and postictal respiratory failure, and since July 1998 had been admitted to a nearby hospital three times. On October 12, 1999, she was again admitted to a nearby hospital with the same symptom, and was transferred from that hospital to ours for evaluation of the recurrent respiratory disorder. Low-grade fever, mild leukocytosis, hypoxemia and bilateral diffuse opacities were observed as previously on chest radiography, and improved within several days without any specific therapy. The negative C reactive protein level, normal cardiac function and faintly bloody bronchoalveolar lavage fluid were also observed. There was no evidence of aspiration pneumonia, infectious disease, or underlying heart or lung disease. Electroencephalography showed spikes in accord with the left temporal lobe, and the cause of the patient's fainting was thought to be temporal lobe epilepsy. After all other causes had been excluded, this case was diagnosed as neurogenic pulmonary edema associated with epileptic seizure. Only about 40 cases of the postictal pulmonary edema have been reported since 1908, and the pathophysiologic mechanism of this condition is still unknown. Neurogenic pulmonary edema associated with epileptic seizure is rare, but the importance of awareness of this condition needs to be emphasized because it is suspected to be the cause of unexpected sudden death in epileptics. We should consider the disease as important in the differential diagnosis of acute respiratory failure associated with epilepsy.
2002The acute-phase protein response to infection in edematous and nonedematous protein-energy malnutrition.Am J Clin NutrImmune structure and function are more compromised in edematous protein-energy malnutrition (PEM) than in nonedematous PEM. Whether the positive acute-phase protein (APP) response to infection is affected remains unknown.We assessed whether children with edematous PEM can mount a general APP response and compared the kinetic mechanisms of the response in children with edematous PEM with those in children with nonedematous PEM.Plasma C-reactive protein, alpha(1)-acid glycoprotein, alpha(1)-antitrypsin, haptoglobin, and fibrinogen concentrations and the fractional and absolute synthesis rates of alpha(1)-antitrypsin, haptoglobin, and fibrinogen were measured in 14 children with edematous PEM, aged 11.4 +/- 2 mo, and 9 children with nonedematous PEM, aged 10.1 +/- 1.4 mo, at 3 times: approximately 2 d after hospital admission (period 1), when they were malnourished and infected; approximately 8 d after admission (period 2), when they were malnourished but free of infection; and approximately 54 d after admission (period 3), when they had recovered.Children with edematous and nonedematous PEM had higher plasma concentrations of 4 of 5 APPs in period 1 than in period 3. The magnitude of the difference in concentration and in the rate of synthesis of the individual APPs was less in the children with edematous PEM than in those with nonedematous PEM. The kinetic data show that the characteristics of the APP response were different in the 2 groups.These results suggest that severely malnourished children can mount only a partial APP response to the stress of infection and that the magnitude of this response is less in those with edema.
2002Procalcitonin in patients with acute myocardial infarction.Wien Klin WochenschrAcute myocardial infarction induces an inflammatory reaction. We related conventional inflammatory parameters including C-reactive protein, erythrocyte sedimentation rate, white blood cell count and axillary temperature to plasma concentrations of procalcitonin in patients with acute myocardial infarction. In a prospective-descriptive study, we evaluated 54 patients with acute myocardial infarction. During a time period of 8 days following myocardial infarction, C-reactive protein, erythrocyte sedimentation rate, white blood cell count and axillary temperature as well as the plasma concentrations of procalcitonin were measured. Maximal procalcitonin remained normal (below 0.5 microgram/L) in patients with uncomplicated acute myocardial infarction. This contrasted with results obtained from patients additionally afflicted by pulmonary edema and cardiogenic shock, in whom maximal procalcitonin increased up to 5.24 micrograms/L. Resuscitation after cardiac arrest and/or concomitant bacterial infection increased procalcitonin to a maximal value of 134 micrograms/L, which was independent of the severity of left heart failure. Conventional inflammatory parameters were all significantly increased even in the absence of cardiac and non-cardiac complications of acute myocardial infarction. In conclusion, procalcitonin increases in patients with acute myocardial infarction only if associated with severe left heart failure, resuscitation after cardiac arrest or in the presence of bacterial infections. Thus, procalcitonin may help to elucidate the etiology of systemic inflammatory response during the early course of acute myocardial infarction.
2002Comparison of Celsior and UW solution in experimental pancreas preservation.J Surg ResThe University of Wisconsin solution (UW) is the gold standard for pancreas preservation. Celsior (CEL) was formulated specifically for heart preservation. Recently, experimental and clinical experience has been reported on the application of CEL to abdominal organs. In this animal study, pancreas preservation with CEL was compared with that in UW solution.Heterotopic, allogeneic pancreaticoduodenal transplantation was performed in female Göttingen Minipigs (n = 12 donors, n = 12 recipients). The grafts were flushed and stored for 6 h at 4 degrees C in UW or CEL. The recipients were randomized into two groups receiving either UW (n = 6)- or CEL (n = 6)-preserved grafts with a follow-up of 5 days. Blood flow (laser Doppler), partial oxygen tension, histological changes, endothelin-1 (plasma, immunohistochemistry), lipase, amylase, trypsinogen activation peptide, and C-reactive protein (CRP) were measured.Partial oxygen tension was lower in the CEL group (P < 0.05). However, blood flow did not differ between UW- and CEL-preserved organs. The histomorphologic analysis of the pancreatic grafts revealed significantly less edema in the UW-preserved organs. Serum levels of amylase, lipase, CRP, and TAP taken from the central venous blood were comparable in the two groups, except for higher amylase values 36 h after reperfusion in the CEL group compared to the UW group (P < 0.05). Likewise, TAP taken from the portal venous effluent of the graft was found to be higher in the CEL group than in UW (P < 0.05). Endothelin-1 serum levels rose significantly during reperfusion without differences between the two groups. ET-1 immunohistochemistry revealed increased local ET-1 during reperfusion in all grafts. However, the ET-1 immunostaining in the CEL group was more pronounced than that in the UW group (P < 0.05).Our results suggest that CEL solution is not as effective in preventing pancreatic ischemia/reperfusion damage as the standard UW solution in experimental pancreas transplantation. Increased ET-1 immunostaining and reduced p(ti)O(2) in the CEL group indicate increased microcirculatory damage in the CEL group.
2002Takayasu arteritis: utility and limitations of magnetic resonance imaging in diagnosis and treatment.Arthritis RheumPrevious studies have confirmed the poor correlation of symptoms, signs, and levels of acute-phase reactants with disease activity in approximately 50% of all patients with Takayasu arteritis (TA). Invasive angiographic studies demonstrate vessel lumen anatomy, but do not provide qualitative information about the vessel wall. Moreover, sequential invasive angiographic studies expose patients to high-dose ionizing radiation and catheter/procedure-related morbidity. The aim of the present study was to determine the utility of new developments in vascular magnetic resonance (MR) technology in patients with TA.Electrocardiogram-gated "edema-weighted" MR was used to evaluate the aorta and its primary branches with regard to the vascular lumen, vessel wall anatomy, and vessel wall edema in 24 TA patients (77 studies). Inclusion criteria were age <50 years and features of TA on both clinical examination and invasive angiographic studies. Patients were stratified based on clinical and laboratory indications of having either unequivocally active disease, inactive disease, or uncertain disease status.MR revealed vessel wall edema in 94% (17 of 18), 81% (13 of 16), and 56% (24 of 43) of studies obtained during periods of unequivocally active disease, uncertain disease activity, and apparent clinical remission, respectively. Westergren erythrocyte sedimentation rate and C-reactive protein values did not correlate with either the clinical assessment of disease activity or MR evidence of vascular edema. The frequency of presumed vascular inflammation (edema), as assessed by MR, in patients who appeared to be in remission was similar to the reported frequency of new angiographic lesions and histopathologic evidence of active disease in surgical specimens from patients thought to be in remission. However, the presence of edema within vessel walls did not consistently correlate with the occurrence of new anatomic changes found on subsequent studies.Inconsistencies in the presence or absence of vessel edema and subsequent anatomic changes have cast doubt on the utility of edema-weighted MR imaging as a sole guide to disease activity and treatment in TA. In this study, the greatest utility of MR was in providing a safe, noninvasive means of assessing changes in vascular anatomy.
2001[Role of inflammation mediators in the pathogenesis of heart failure].Ital Heart J SupplA number of factors are involved in congestive heart failure pathogenesis. Among these, inflammatory mediators could have a crucial role. Patients with congestive heart failure show increased plasma levels of "proinflammatory cytokines", in particular tumor necrosis factor-alpha and interleukin-6. Clinical and experimental models have demonstrated that these cytokines induce left ventricular dysfunction, pulmonary edema, ventricular remodeling, skeletal muscle abnormalities, myocyte apoptosis and endothelial dysfunction, suggesting the possibility that increased plasma concentration of cytokines could not be just an epiphenomenon, but an effective pathogenetic mechanism of disease progression. Additional inflammatory proteins involved in the acute phase response could play a part in the pathogenesis of heart failure. Pentraxin 3 is a prototypical long pentraxin, structurally related, although with different functions, to C-reactive protein, is produced by immune system cells, fibroblasts and particularly by cardiac endothelial cells and myocytes, as demonstrated in murine and human models. Its synthesis is rapidly induced after exposition to bacterial lipopolysaccharide and proinflammatory cytokines, as interleukin-1beta and tumor necrosis factor-alpha. In heart diseases, pentraxin 3 could be involved in the acute local inflammatory response to myocardial injury (e.g. necrosis) and in heart failure pathogenetic mechanisms, but its exact role is not yet settled. Defining the specific part played by these molecules in the pathogenesis of heart failure could lead to new therapeutic approaches in the treatment of cardiac insufficiency.
2000Transient osteoporosis of the hip during pregnancy.J Nippon Med SchWe report the clinical features of and MRI findings in transient osteoporosis of the hip during pregnancy. The study population consisted of 4 patients with a mean age of 33 years. The mean gestational age at onset was 31 weeks (range: 27 to 35 weeks). The main symptoms consisted of a weight-bearing pain in the hip and gait disturbance. The pain occurred suddenly and was of unknown cause and became severe within 2 to 3 weeks. X-ray examinations showed diffuse osteoporosis in the femoral head and neck. Moreover in 3 patients, similar lesions were also found in the lumbar spine or the knee. MRI obtained from 3 patients revealed a mottled low-signal lesion extending from the femoral head and neck on T1-weighted images and a high-signal lesion in the bone marrow suggesting edema on T2-weighted images. Mild elevation of C- reactive protein was shown in 2 patients. Conservative treatments with the limitation of weight bearing and bed rest were performed for all patients, and nonsteroidal anti-inflammatory drugs were given to 3 patients. The hip pain began to decline from 8 to 14 weeks after the onset, and completely disappeared from 14 to 24 weeks. X-ray examinations showed that osteoporotic lesions tended to improve at 10 to 14 weeks, on MRI, a high-signal lesion suggesting bone marrow edema resolved together with relief of the pain. No recurrence was found in any patients at mean follow-up of 70.8 months.
2000[A case of Leber's neuroretinitis].J Fr OphtalmolDescribed in 1916 by Theodore Leber, this rare syndrome characterized by low visual acuity, papillary edema, and a macular star (dry exsudates) occurs classically in the 30 to 40 year age range but also as frequently in children. The visual prognosis is excellent. An infectious cause is found in almost all cases. Case report A 34-year-old man consulted for declining visual acuity of the right eye which began suddenly without pain and was preceded by a flu-like syndrome lasting two weeks. Visual acuity on the right side was 2/10 P6, there was optic disk edema associated with dry macular exsudate (macular star) and a paleness of the posterior pole progressing to the periphery and readily visualized on the angiography, and a central scotome, but no dyschromatopsy. The left eye was strictly normal. Laboratory tests showed an erythrocyte sedimentation rate at 45, C reactive protein at 61, normal red cell count and minimal transaminase elevation. Spinal tap showed: 3 elements/mm(3), protein 0.28g/l, 18% gammaglobulins. Serology tests were negative. Brain imaging was normal.Corticosteroid flashes for three days were initiated and the patient was seen again two weeks later with clear clinical improvement. Visual acuity was 6/10 P2 with considerable resorption of the edema.This case is a typical illustration of acute Leber's neuroretinititis, probably caused by viral infection. The cerebrospinal fluid tests and brain imaging ruled out multiple sclerosis, and serology tests for syphilis, tuberculosis, Lyme disease and possible parasite infection were negative.Acute lever's neuroretinitis is an uncommon condition which must be distinguished from inflammatory optic neuropathy, particularly in multiple sclerosis which has a very different prognosis and clinical course.
2000[A child without edema in spite of albumin deficiency].Ned Tijdschr GeneeskdDuring extended investigation of a newborn girl with recurrent respiratory tract infection a continuous elevated blood sedimentation rate was noted together with a normal level of C reactive protein. This abnormality could be explained by analbuminaemia, causing a change in concentration of several other proteins such as transferrin. It was striking that this girl without albumin showed no signs of oedema. This lack of oedema could be explained by a decrease of oncotic pressure in the interstitium. Analbuminaemia is an autosomal recessive disorder. At follow-up the girl was still without complaints after 6 years.
2000Unclassified connective tissue disease presenting as cardiac tamponade: a case report.Jpn Circ JThis report describes a case of cardiac tamponade as the initial manifestation of unclassified connective tissue disease (UCTD). A 68-year-old Japanese woman was admitted to hospital because of dyspnea and edema. She had undergone a radical left mastectomy for the treatment of breast cancer 18 years before. On admission, bilateral leg edema, hepatomegaly, and a paradoxical pulse were noted on physical examination. The erythrocyte sedimentation rate was elevated and the C-reactive protein was 2.8 mg/dl. Antinuclear antibodies and anti-SS-A/Ro antibodies were present. The scl-70 and anticentromere antibodies were elevated. Chest radiography showed cardiomegaly. Echocardiography revealed a large pericardial effusion, but the pericardial fluid did not contain malignant cells or bacteria. She did not meet the diagnostic criteria for any known connective tissue diseases, so was diagnosed with cardiac tamponade due to UCTD. Prednisolone (30 mg/day) was administered, which resulted in a gradual resolution of the pericardial effusion. Although connective tissue diseases are known to cause pericardial effusion, cardiac tamponade as the initial manifestation of the disease in the absence of other symptoms is quite rare.
2000[Diabetic muscle infarct].Dtsch Med WochenschrA 64-year-old diabetic man with secondary failure of treatment with oral hypoglycemic agents was admitted to our clinical department to initiate insulin therapy. The patient was otherwise in good health. Before his dismissal he acutely developed symptoms of pain in his left calf. In addition, the patient was unable to move his left leg and presented palpable pea-sized nodules of his left calf.Laboratory investigations revealed elevated serum creatine kinase levels on day two after the onset of clinical symptoms (peak value: 2238 U/I). There was evidence for antinuclear antibodies, c-reactive protein was normal. An ultrasound investigation showed a focal edema or bleeding located to the musculus gastrocnemius. Duplex-sonography excluded thrombosis or embolisation. Magnetic resonance imaging showed a diffuse enhancement of signal intensity within the musculus soleus and in areals of the musculus gastrocnemius, as signs of increased blood supply. All clinical findings were consistent with the diagnosis of diabetic muscle infarction.Under symptomatic treatment with tramadol, diclofenac ointment, and fragmented heparin serum creatine kinase returned to normal levels (105 U/I) within 14 days. In accordance, symptoms of local pain disappeared completely. After two weeks of treatment the patient was able to move his leg without pain.This is the first presentation of a patient with diabetic muscle infarction from the onset of symptoms until full recovery. In addition, this case confirms previous descriptions that this condition can be diagnosed by clinical and sonographic findings in combination with magnetic resonance imaging without invasive histologic techniques.
2000HSV-1--induced acute retinal necrosis syndrome presenting with severe inflammatory orbitopathy, proptosis, and optic nerve involvement.OphthalmologyTo present a unique case in which orbital inflammation, proptosis, and optic neuritis were the initial symptoms of acute retinal necrosis (ARN). The clinical presentation of ARN, as well as the currently recommended diagnostic procedures and guidelines for medical treatment of ARN, are summarized.Interventional case report.Polymerase chain reaction (PCR) techniques were made on the vitreous for cytomegalovirus, Epstein-Barr virus, herpes simplex virus (HSV), varicella zoster virus, and toxoplasmosis. A full laboratory evaluation was made together with HLA-typing and serologic tests measuring convalescent titers for HSV and other micro-organisms. Magnetic resonance imaging scan, computed tomography (CT) scan, and fluorescein angiographic examination were performed. The patient was treated with acyclovir and oral prednisone.The patient was evaluated for initial and final visual acuity and for degree of proptosis, periocular edema, and vitreitis.The first symptoms and signs of ARN were eye pain, headache, proptosis, and a swollen optic nerve on CT scan. Other than increased C-reactive protein, all blood samples were normal. PCR was positive for HSV-type I in two separate vitreous biopsies. The patient had the strongly ARN-related specificity HLA-DQ7.This is the first report of HSV-induced ARN presenting with inflammatory orbitopathy and optic neuritis. Polymerase chain reaction for HSV-1 was positive more than 4 weeks after debut of symptoms, which is a new finding. The combination of severe vitreitis and retinal whitening, with or without proptosis, should alert the clinician to the possibility of herpes infection and treatment with intravenous acyclovir started promptly.
1999Early detection of sacroiliitis on magnetic resonance imaging and subsequent development of sacroiliitis on plain radiography. A prospective, longitudinal study.J RheumatolTo investigate the diagnostic value of magnetic resonance imaging (MRI) in the detection of early sacroiliitis.Twenty-five consecutive HLA-B27 positive patients with inflammatory low back pain and < or = grade 2 unilateral sacroiliitis on conventional radiography (modified New York criteria) were studied. Erythrocyte sedimentation rate, C-reactive protein, plain radiography (PR), and MRI of the sacroiliac (SI) joints were obtained at study entry and PR of the SI joints after 3 years. Each radiograph and MR image set was interpreted independently. SI joints were scored according to the modified New York Criteria for radiological sacroiliitis. MRI scans were also scored for the presence of subchondral marrow edema. The relationship between > or = grade 2 sacroiliitis (by modified New York criteria for radiological sacroiliitis) shown on MRI and the subsequent development of > or = grade 2 sacroiliitis on PR after 3 years was investigated.At study entry > or = grade 2 sacroiliitis was found on MRI in 36 of 50 SI joints. Edema was found in 20 of 50 SI joints. After 3 years > or = grade 2 sacroiliitis was found on PR in 21 of 44 SI joints. The positive predictive value of > or = grade 2 sacroiliitis on MRI for the development of > or = grade 2 sacroiliitis on PR after 3 years was 60%; sensitivity was 85% and specificity 47%.Our data suggest that MRI of the SI joints can be used to identify sacroiliitis earlier than PR.
1999Exacerbation of acute pancreatitis in the presence of chronic liver injury in rats, with special reference to therapeutic efficacy of prostaglandin E1.PancreasThe pathophysiology of acute pancreatitis accompanied by chronic liver injury, and the therapeutic efficacy of prostaglandin (PG)E1 were studied experimentally in rats. Chronic liver injury was produced by subcutaneous administration of CCl4. Acute pancreatitis was induced by the closed duodenal loop (CDL) method, immediately after which PGE1 (60 ng/kg/min) was infused intravenously via the jugular vein. Serum levels of amylase, alpha2-macroglobulin-trypsin complex (alpha2M-TRY), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) were determined before and at 3 and 6 h after the onset of acute pancreatitis. Rats without administration of CCl4 served as controls. Serum amylase levels were lower in the liver injury (LI) group than in the normal liver (NL) group at 3 and 6 h. PGE1 had no effect on amylase levels in either group. Serum alpha2M-TRY levels were similar in the two groups at 3 h, but significantly higher in LI than in NL at 6 h. PGE1 tended to decrease alpha2M-TRY levels only in LI. Serum CRP levels were significantly more elevated in LI than in NL at 0, 3, and 6 h. PGE1 decreased CRP levels only in LI. Serum TNF-alpha concentrations were higher in LI, especially at 6 h. PGE1 reduced TNF-alpha levels in LI. Pancreatitis severity scores were significantly higher in LI. PGE1 significantly decreased the severity scores only in LI. Fat necrosis scores were significantly lower in LI. Histologically, interstitial edema was much more prominent in NL than in LI, whereas interstitial hemorrhage was more severe in LI at 3 and 6 h. PGE1 lessened the hemorrhage in LI. The extent of both vacuolization and necrosis of acinar cells was similar for both groups and tended to be improved by PGE1. It is concluded that acute pancreatitis becomes much more serious in the presence of chronic liver injury, and that PGE1 can ameliorate the exacerbated lesions, probably by improvements in blood flow through the pancreatic tissue.
1999Rheumatoid arthritis in the elderly.Exp GerontolRheumatoid arthritis of late onset (LORA) referred as the subset of rheumatoid arthritis with age of onset over 60 years old, seems to differ from young onset disease (YORA) by a more equal sex distribution, a higher frequency of abrupt disease onset, more large joint complaints and less extraarticular features. Different immunogenetic associations are also reported between the two age groups. The percentages of rheumatoid factor (RF) and C-reactive protein (CRP) positivity differ in various surveys in both groups examined. Favorable prognostic factors could be considered the absence of rheumatoid factor activity and the presence of pitting edema of the hands. Greek patients with LORAS appear not to have differences in comparison to their younger counterparts. Disease modifying drugs and low doses of prednisone are the mainstream of therapy with need for further caution in the aged group.
1999[POEMS syndrome with chronic renal failure].Med Klin (Munich)A 43-year-old male was admitted to the hospital because of subfebrile temperatures since 3 months, weight loss of 9 kilogramms and lateral foot pains with bilateral leg edema. Over the last years, the patient had consulted a doctor several times for upper respiratory infections, orchitis and a spinal neck syndrome. At the physical examination, we found a temperature of 37.4 degrees C, no rales, no crackles at auscultation of the lung, bilateral ankle edema and livid, pressure-dolent skin changes at the lateral margins of both feet. The blood pressure was 170/100 mmHg.The following pathologically laboratory results were found: erythrocyte sedimentation rale (ESR) 35/55 mm n. W., C-reactive protein (CRP) up to 39 mg/l, leucocytes up to 13.5/nl, LH and FHS were elevated corresponding to hypergonadotropic hypogonadism, renal failure with at the beginning a selective glomerular proteinuria, as well as a monoclonal IgG-gammopathy. The bone marrow aspiration as well as the bone marrow biopsy revealed neither plasmocytoma nor a malignant systemic disease. The ultrasound examination showed enlarged liver, spleen, and kidneys. TREATMENT AND FOLLOW-UP: After excluding a connective tissue disease and an infection and with the missing proof of a malignant tumor treatment was started with parenteral methylprednisolon 500 mg on 3 consecutive days under the hypothesis of classic panarteriitis nodosa, even when multiple biopsies were negative. Under the treatment, the elevated inflammatory parameters and renal failure improved, but deteriorated quickly after discontinuation of the corticosteroid medication. The second kidney biopsy showed a chronic scaring glomerulopathy of the hemolytic uremic syndrome type. In the follow-up the renal insufficiency was improved by corticosteroids. With the manifestation of a bilateral sensory polyneuropathy in January 1994, the diagnosis of a POEMS syndrome was most likely.According to the literature, up to 50% of the cases with POEMS syndrome reveal renal failure. Most times a glomerular microangiopathy is shown histologically. A treatment trial with corticosteroids is justified.
1999Vascular endothelial growth factor in acute Kawasaki disease.Am J CardiolVascular endothelial growth factor (VEGF), also known as vascular permeability factor, is an important regulator of angiogenesis and blood vessel permeability. Kawasaki disease (KD) is characterized by systemic vasculitis with increased vascular permeability, implying a possible role of VEGF in KD. To elucidate the involvement of VEGF in the pathogenesis of KD, we investigated 30 patients with acute KD, comparing the time course of plasma VEGF levels (n = 123) with clinical symptoms and laboratory findings. Compared with control values, the peak levels of plasma VEGF were significantly elevated (38+/-26 vs 244+/-248 pg/ml, p <0.001). The VEGF levels at the appearance of skin rash and/or edema of hands and feet were also elevated to 176+/-163 pg/ml (p <0.001). In 7 patients (23%), the plasma VEGF levels remained increased after the resolution of the skin rash and peripheral edema. The VEGF levels were independent of gamma globulin therapy and levels of serum albumin and C-reactive protein. We also measured the plasma levels of transforming growth factor-beta1 (TGF-beta1) and tumor necrosis factor alpha, both of which can upregulate VEGF in vitro. The plasma levels of VEGF were highly correlated with those of TGF-beta1 (n = 63, r = 0.73, p <0.001) but not with those of tumor necrosis factor alpha. These findings suggest that the production of VEGF is increased and may be upregulated by TGF-beta1 in acute KD. VEGF may be involved in the hyperpermeability of local blood vessels in acute KD.
1998Right-sided sciatalgia complicating Crohn's disease.Am J GastroenterolNeurological complications of Crohn's disease due to involvement of the extradural space are extremely rare. A 40-yr-old woman with Crohn's disease affecting the terminal ileum presented with a right-sided sciatalgia. The patient did not complain of diarrhea or constipation. The serum fibrinogen and the C-reactive protein were elevated. Magnetic resonance imaging and computed tomography scan of the abdomen and pelvis demonstrated a mass in front of the sacrum up to but not including the first sacral vertebra. Surgical intervention, with resection of 15 cm of terminal ileum, led to the complete resolution of symptoms. In this case, the underlying cause of the neurological symptoms was most likely an infiltration of the right lumbosacral nerve caused by edema and inflammation of the terminal ileum in the vicinity of the presacral space. Unexplained lumbosacral neurological symptoms in a patient with Crohn's disease necessitate a magnetic resonance imaging or computed tomography scan to detect potential neurological compression.
1998[RS3PE: a clinical diagnosis, a prognosis more simple than its name].Rev Med InterneRS3PE syndrome (remittive symmetrical seronegative synovitis with pitting edema) was first described by MacCarthy in 1985. It is a rare type of seronegative polyarthritis occurring in the elderly.Retrospective report of 13 cases (including eight male and five female patients; mean age 76.7 +/- 3.7 years) and search for previously reported cases, using the Medline database.Pitting edema was present at onset of disease in nine cases. Joint arthritis was bilateral, occurring in the wrist (13 cases), shoulder (six cases), elbow (six cases), knee (six cases), ankle (four cases), metacarpophalangeal (four cases) and hip (one case). Radiographies were normal. Mean erythrocyte sedimentation rate was 62 +/- 19 mm at the first hour and mean C-reactive protein level was 73 +/- 35 mg/L. Mild cholestasis was present in four of the seven patients for whom data were available. HLA B7 was present in five out of 12 cases (42%). Improvement was favorable, occurring over 7 months. Mean follow-up was 22.2 months. Fifty-nine other cases have been described in the literature. This syndrome, which affects the elderly, appears to be rare. Its clinical presentation is quite constant, with sudden onset, symmetrical polyarthritis and pitting edema. Its evolution, often long, is favorable. Rheumatoid arthritis and polymyalgia rheumatica are the main differential diagnoses.Due to its favorable outcome and the usefulness of a mild corticotherapy, this syndrome, though rare, should be diagnosed where necessary in elderly patients.
1998[Isoniazid-induced pneumonitis].Nihon Kokyuki Gakkai ZasshiAn 82-year-old man was treated with isoniazid (INH) because of a low-grade fever. On the 9th day of treatment, dry coughing and general malaise developed. On the 30th day, he was admitted to our hospital. A chest-X ray film showed infiltrative shadows in the right middle and lower lung fields, but a chest CT scan showed an abnormal lung density in the right lower lobe. Abnormal laboratory findings included leucocytosis, liver dysfunction, hypoxemia, low vital capacity, low diffusing capacity and a high level of C-reactive protein. A differential cell count of the bronchoalveolar lavage fluid (BALF) showed many neutrophils and lymphocytes; examination of a specimen obtained by transbronchial lung biopsy (TBLB) revealed edema of alveolar walls, lymphocyte infiltration, and proliferation of type II alveolar epithelial cells. A drug lymphocyte stimulation test (DLST) against INH was positive. After discontinuation of INH, symptoms resolved, laboratory findings became normal, and the infiltrative shadows in the right middle and lower lung fields disappeared. The clinical course and the findings of BALF, TBLB, and DLST suggested the diagnosis of pneumonitis caused by INH.
1997Percutaneous transhepatic gallbladder drainage for acute acalculous cholecystitis following cardiovascular surgery.J Cardiovasc Surg (Torino)Four (1.2%) out of 321 patients required percutaneous transhepatic gallbladder drainage (PTGBD) following cardiovascular surgery. Cholecystitis was initially suspected based upon the occurrence of postoperative fever and the results of abdominal X-ray films. The main physical finding was tenderness of the right upper quadrant abdomen in all patients. Spontaneous pain and Blumberg's sign were not apparent. Distension of the gallbladder and sludge in the gall-bladder were detected in all four patients by ultrasonography, but calculi were not observed. Thickening and edema of the gallbladder wall, generally suggestive of cholecystitis, were observed in only one patient. PTGBD was performed from 5 to 43 (mean 16) days after surgery. The drained fluid was concentrated bile and not purulent. High fever dropped and serum transaminase and C-reactive protein levels decreased within three days after PTGBD. Bacteriologic examinations of the bile and arterial blood were negative in all cases. No complications as a result of PTGBD introduction occurred. PTGBD is a safe and effective procedure, and therefore should be actively performed even in the early phase of acute cholecystitis.
1997[A case of polymyalgia rheumatica with swelling and pitting edema of the distal lower extremities].Nihon Ronen Igakkai ZasshiWe report a case of an 82-year-old woman with polymyalgia rheumatica (PMR) associated with swelling and pitting edema of the lower extremities. The patient had been previously admitted because of PMR in 1990, but there was no history of swollen extremities. In July 1996, at another hospital, she was again diagnosed as having PMR on the basis of pain in the neck, shoulders and lower back. Administration of prednisolone was followed by improvement of the symptoms. Four months later, similar pain recurred and swelling of the lower extremities was noted. On admission, the erythrocyte sedimentation rate was 86 mm/h, and C-reactive protein was 15.5 mg/dl. Reviewing the previous treatment, it was ascertained that her clinical deterioration was due to premature reduction of the steroid dosage. The cause of the swelling of the lower extremities was unlikely to be heart, liver, kidney or endocrine disease. Prednisolone was increased from 2.5 mg to 10 mg daily with marked improvement in all the symptoms including the swelling and pitting edema. In 1996, a study reported distal extremity swelling with pitting edema as a manifestation of PMR, which mostly developed concurrently with proximal symptoms or during relapses of PMR. The swelling responded poorly to non-steroidal antiinflammatory drugs but promptly to corticosteroids. The distal swelling was reported to be tenosynovitis and synovitis of the surrounding structures. The present case appears similar to that report. More studies of PMR need to be done.
1997[Microscopic polyangiitis and pulmonary fibrosis in a patient who died of Candida pneumonia and intra-alveolar hemorrhage].Nihon Kyobu Shikkan Gakkai ZasshiA 74-year-old man was admitted to our hospital because of edema of the lower legs, fever, and increasing fatigue. Laboratory evaluation revealed proteinuria, microhematuria, leukocytosis, thrombocytosis, anemia, a high level of C-reactive protein. A test for myeloperoxidase-antineutrophil cytoplasmic antibodies was highly positive. Microscopic polyarteritis nodosa was diagnosed and therapy with prednisolone was begun. Examination of a renal biopsy sample showed necrotizing crescentic glomerulonephritis. A chest roentgenogram and CT scan disclosed bilateral basilar interstitial changes. Six months later, the patient was admitted again because of disturbance of consciousness, malnutrition, and hyponatremia. After admission, alveolar infiltrates developed in the right lung and the patient died on the 5th hospital day as a result of respiratory failure. An autopsy revealed Candida pneumonia of the right lung and massive intra-alveolar hemorrhage, which was believed to have caused the respiratory failure. Other findings were usual interstitial pneumonia, cellular small-vessel angiitis in the lungs, and healed angiitis in the kidneys and liver. In this case of microscopic polyangiitis and chronic interstitial pneumonia, steroid therapy was effective against the angiitis, but the patient died of an opportunistic infection and alveolar hemorrhage.
1997[Surgical therapy of severe acute pancreatitis].Schweiz Med WochenschrThere is some evidence that the incidence of acute pancreatitis is increasing worldwide. Improved treatment concepts, especially in the severe course of the disease, have significantly reduced formerly high mortality. According to the different clinical courses it is of the utmost importance for the therapeutic approach to this disease to differentiate between mild (morphologically characterized as edema) and severe (intra- and extrapancreatic necroses) as early as possible. In this respect, contrast-enhanced CT scanning and the determination of so-called necrosis indicating parameters (e.g. C-reactive protein) have been established as the "gold-standard". While patients with acute edematous pancreatitis are successfully treated in a normal ward, patients with a proven necrotizing course of the disease should undergo intensive monitoring and maximum intensive care therapy in the ICU. Additionally, these latter patients should receive antibiotics which are capable of penetrating the pancreas and the pancreatic necroses in bactericidal concentrations. It seems more and more evident that only patients under this treatment regimen who develop infected pancreatic necrosis and sepsis are candidates for surgical intervention. Infected pancreatic necrosis can be easily diagnosed with a high level of safety and reliability by fine needle puncture and aspiration of pancreatic necrosis and fluid collections under imaging-guided procedures. Patients with sterile necrosis respond in most cases to intensive care therapy and in these patients the indication for surgery will be only exceptional. Surgery should be performed as late as possible to ensure sufficient demarcation of the necroses. In our experience the best surgical treatment modality for infected pancreatic necrosis is necrosectomy combined with postoperative continuous local lavage of the retroperitoneum. Mortality of severe acute pancreatitis has been reduced under this treatment concept to below 10%.
1997Inflammatory mediators in children with protein-energy malnutrition.Am J Clin NutrEdema is a typical sign in kwashiorkor, which is present in a subset of patients with protein-energy-malnutrition (PEM). The pathophysiology of this edema is not well established. One of the abnormalities found in kwashiorkor is reduced concentrations of antioxidants, suggesting a compromised capacity to neutralize free radicals, which are known to induce tissue damage. We have studied plasma concentrations of several mediators of the inflammatory cascade. Concentrations of interleukin 6 (IL-6), C-reactive protein, and the soluble receptors of tumor necrosis factor alpha (sTNFR-p55 and sTNFR-p75) are greater in children with PEM, particularly in those with kwashiorkor, whereas soluble receptors of IL-6 (sIL6R-gp80) and IL-1 receptor antagonist concentrations are not significantly different from those of healthy children. In addition, concentrations of IL-6, sTNFR-p55, and sTNFR-p75 are greater in kwashiorkor patients irrespective of the presence of infection. Antioxidant status, as determined by plasma concentrations of glutathione and vitamin E, is significantly reduced in kwashiorkor patients. These data support the notion that children with edematous malnutrition show increased inflammatory reactivity that may contribute to edema formation.
1997[Clinical application of interleukin-6 receptor antibody].Nihon Rinsho Meneki Gakkai KaishiInterleukin-6 (IL-6) is a pleiotropic cytokine which shows multiple biological functions. Pathological significance of IL-6 has been elucidated in various diseases including multiple myeloma, Castleman's disease, and rheumatoid arthritis. Thus the blockade of IL-6 signal transduction may be therapeutically effective for these diseases. For this purpose, humanized anti-IL-6 receptor antibody was prepared, and its therapeutic efficacy has been examined. Immediately after administration of humanized anti-IL-y receptor antibody to the patients with multiple myeloma, fever and systemic edema disappeared followed by the stability of M-protein which had been rapidly increased before the treatment. Humaniged anti-IL-6 receptor antibody also improved not only the chronic inflammatory symptoms but also laboratory findings such a hemoglobin, C-reactive protein, erythrocyte sedimentation rate observed both in Castleman's disease and in rheumatoid arthritis. The data suggest that the blockade of IL-6 signal transduction can be a new therapeutic approach based on the pathological significance of IL-6 in these diseases.
1997[An elderly patient with infectious endocarditis complicated with congestive heart failure due to mitral and tricuspid regurgitation].J CardiolA 77-year-old man was referred to our hospital on October 2, 1995 because of fever and left mandibular pain beginning three months before admission. His blood pressure was 90/60 mmHg. A grade III/VI pansystolic murmur was heard over the cardiac apex. The liver was palpable 4 cm below the right costal margin. Lower extremity edema was present bilaterally. White blood cell count was 7,030/mm3 and C-reactive protein was 2.54. Enterococcus faecalis was identified by the blood culture. The diagnosis was infective endocarditis associated with congestive heart failure. He was treated by administration of antibiotics and diuretics. Mitral valve replacement and tricuspid annuloplasty were performed on October 19 because of progressive congestive heart failure with oliguria. The surgical intervention was successful despite the presence of multiple risk factors: high age, emergency, congestive heart failure and active infection. His condition improved dramatically after the operation and he was discharged two months later. Surgical intervention for infective endocarditis was a significant high-risk procedure in this uncontrollable and elderly case. This successful result suggests the indication for the timing of surgery.
1996Evidence against an increase in capillary permeability in subjects exposed to high altitude.J Appl Physiol (1985)A potential pathogenetic cofactor for the development of acute mountain sickness and high-altitude pulmonary edema is an increase in capillary permeability, which could occur as a result of an inflammatory reaction and/or free radical-mediated injury to the lung. We measured the systemic albumin escape by intravenously injecting 5 muCi of 125I-labeled albumin and the plasma concentrations of cytokines, F2-isoprostanes (products of lipid peroxidation), and acute-phase proteins in 24 subjects exposed to 4,559 m. Ten subjects developed acute mountain sickness, and four subjects developed high-altitude pulmonary edema. The transcapillary escape rate of albumin was 6.9 +/- 2.0%/h (SD) at low (550 m) and 6.3 +/- 1.9%/h at high (4,559 m) altitude (P = 0.23; n = 24). The subjects with high-altitude pulmonary edema had a modest but insignificant increase in the transcapillary escape rate of albumin (4.6 +/- 1.9%/h at low vs. 5.7 +/- 1.9%/h at high altitude; P = 0.42; n = 4). Plasma concentrations of fibrinogen, alpha 1-acid glycoprotein, C-reactive protein, and interleukin-6 were unchanged in the early phases and significantly increased by the end of the observation period in the subjects with high-altitude pulmonary edema, whereas tumor necrosis factor-alpha and F2-isoprostanes did not change at all. This suggests that the inflammatory reaction was rather a consequence than a causative factor of high-altitude pulmonary edema. In summary, these data argue against a dominant role for increased systemic capillary permeability in the development of acute mountain sickness and high-altitude pulmonary edema.
1996Changes in indicators of inflammation after eccentric exercise of the elbow flexors.Med Sci Sports ExercThis study examined muscle swelling and changes in inflammatory markers in the blood following eccentric exercise-induced muscle damage. Subjects (N = 14) who had not been involved in a resistance training program performed 24 maximal eccentric actions of the elbow flexors. Muscle swelling was assessed by measures of the upper arm circumference (CIR), ultrasonography (USG), and magnetic resonance imaging (MRI). Plasma concentrations of interleukin-1 alpha, interleukin-1 beta, interleukin-2, interleukin-6, tumor necrosis factor-alpha, and plasma levels of C-reactive protein, cortisol, and zinc were analyzed. Established indicators of muscle damage (maximal isometric force, range of motion, muscle soreness, and plasma creatine kinase, aspartate aminotransferase, and lactate dehydrogenase activities) were also measured. All measures, including CIR and USG, except for MRI, were assessed immediately before and after and for 5 d post-exercise. MRI was taken at pre- and 1, 3, 6, 10, 23, 31, and 58 d post-exercise. All muscle damage indicators changed significantly after exercise. A large increase in CIR (> 20 mm) was found 4-5 d after exercise, and this coincided with USG, showing an increase in muscle thickness. The echointensity of USG increased with the enlargement of the elbow flexors. MRI displayed enlargement of the biceps brachii and brachialis cross-sectional area that started at 1 d, and lasted until 23 d, post-exercise. The most profound increase in the enlargement and signal intensity of the MRI was found 3 or 6 d after exercise. However, none of the plasma levels of inflammatory makers showed significant muscle swelling, which is indicative of muscle edema, but the inflammatory responses after exercise appear to be different from those accompanying infection or tissue injury.
1994[Orbital cellulitis in children].Arch PediatrBecause the potential for complications is great, orbital cellulitis must be recognized promptly and treated aggressively.The files of 38 children admitted from 1988 to 1993 because of orbital or periorbital cellulitis were retrospectively analyzed. Clinical findings included fever, edema, pain, rhinorrhea, conjunctivitis, limitation of eye movement, loss of vision and ophthalmoplegia. All patients had hemogram, ionogram, blood cultures, search for soluble antigens in blood and/or urine, C-reactive protein measurement; they also had roentgenographic examination of the sinuses, orbital ultrasonography and/or CT scan in patients with retroseptal cellulitis. All patients were given systemic antibiotic therapy.Thirty-five patients had preseptal and three retroseptal cellulitis. Preseptal cellulitis was associated to sinusitis in 17 patients, to ocular infection in 11 (seven conjunctivitis and four dacryocystitis), to an infected wound in six. Seventy-three per cent of the patients with ocular infection were less than 2 years of age with a significant preponderance of girls (64%). The three cases of retroseptal cellulitis were associated to sinusitis. Orbital echography was performed in five cases, permitting to recognize the three cases of retroseptal cellulitis that was confirmed by CT scan. Twenty-five of the 38 children were given oral antibiotics during the days preceding admission, explaining the relative rarity of positive bacteriological findings (seven cases). Thirty-five of the 38 children were given IV cefotaxime + fosfomycin, associated to netromycin in 16 cases. Mean duration of treatment was 3 days (range: 1-7). IV antibiotherapy was followed by oral amoxicillin-clavulanic acid administration in 25 patients and pristinamycin in 11.Orbital cellulitis in children, more frequently preseptal, have a good prognosis under adapted antibiotherapy. A retroseptal cellulitis requires multidisciplinary management because of the risk of extension of infection from the orbit to the eye and/or into the cranial cavity.
1994A case of uveitis associated with idiopathic retroperitoneal fibrosis.Am J OphthalmolWe treated a patient with nongranulomatous panuveitis associated with idiopathic retroperitoneal fibrosis who had symptoms of abdominal pain, severe fever, leg edema, and blurred vision. A high C-reactive protein level, a high erythrocyte sedimentation rate, anemia, and abnormalities of the immune system were seen. Retrograde pyelography disclosed persistent ureteral obstruction. A computed tomographic scan and magnetic resonance imaging showed a dense plaque of fibrous tissue around the kidney and hydronephrosis. Biopsy disclosed fibrosis infiltrated with lymphocytes, plasma cells, histiocytes, and eosinophils. A moderate degree of cellular inflammation in the anterior chamber and cystoid macular edema were present at ocular examination. We believe idiopathic retroperitoneal fibrosis to be a new cause of uveitis of suspected autoimmune origin.
1994Evaluation of dexamethasone for reducing postoperative edema and inflammatory response after orthognathic surgery.J Oral Maxillofac SurgA randomized, prospective, double-blind study was conducted to determine the efficacy of intravenous dexamethasone in reducing postoperative edema after bilateral sagittal split osteotomies of the mandible. Twenty-three patients were enrolled in the study and randomly assigned to one of the three groups. Each patient received one preoperative infusion and three postoperative infusions every 6 hours. Seven patients served as controls and received placebos for all infusions. Eight patients received dexamethasone, 16 mg preoperatively and three placebo postoperative doses. Eight patients received dexamethasone, 16 mg preoperatively and three 8-mg postoperative doses. Facial edema was quantified by computer scanning of standardized photographs. The underlying inflammatory process also was measured using C-reactive protein, erythrocyte sedimentation rate, and complete blood counts. Five sets of photographic and laboratory data were obtained for each patient: preoperative, day of surgery, and postoperative days 1, 2, and 3. Patients receiving dexamethasone demonstrated significantly less postoperative edema only on postoperative day 1 (P < .05) when measured photographically. C-reactive protein was significantly reduced on postoperative days 1, 2, and 3 (P < .05) in both dexamethasone groups. No significant difference was found between the two dexamethasone groups. Measurement of C-reactive protein seems to be the most sensitive method for comparing the effect of dexamethasone on postoperative inflammation. Preoperative intravenous dexamethasone significantly reduced postoperative inflammation and its associated edema after orthognathic surgery.
1993Comparison of bone scan, computed tomography, and magnetic resonance imaging in the diagnosis of active sacroiliitis.Semin Arthritis RheumQuantitative bone scan (QBS), computed tomography (CT), and magnetic resonance imaging (MRI) have each been used to confirm the diagnosis of active sacroiliitis (SI) in patients with low back pain (LBP). The authors prospectively evaluated 19 patients referred for symptoms of possible inflammatory LBP (group I), 26 seronegative spondyloarthropathy (SNSP) patients with LBP (group II, inflammatory or mechanical), and 5 SNSP patients without LBP (group III) to determine which radiological scan alone or in combination with other serological tests (Westergren erythrocyte sedimentation rate, C-reactive protein, HLA-B27, immunoglobulin A) was most useful in confirming a clinical diagnosis of active inflammatory SI. All patients were followed up for a minimum of 1 year to confirm the clinical diagnosis and evaluate response to therapy. Eight of 19 group I patients had active SI clinically or on plain radiographs on follow-up evaluation. Of these patients, 5 had abnormal QBS (71%), 3 had abnormal CT scans (38%), and 8 had abnormal MRI scans (100%, type I lesions). These type I MRI lesions were indicative of active inflammation manifested as subcortical bone marrow edema. The remaining 11 group I patients had negative scans for SI. Ten of 26 group II patients with LBP had SI diagnosed clinically and confirmed with positive QBS (60%), CT (100%), and MRI (100%, type I lesions). The remaining 16 group II patients had mechanical LBP without active SI clinically and had negative QBS (88%), CT (19%), and MRI (100%, normal or type II lesions). These type II MRI lesions represented old postinflammatory lesions with either fibrosis or fat replacement. All 5 group III patients had negative scans for active SI. Three patients (2 group I and group II) with inflammatory SI treated with sulfasalazine showed marked improvement on serial MRI scans. Westergren erythrocyte sedimentation rate, C-reactive protein, immunoglobulin A, and CT scan alone or in combination with other tests were not reliable predictors of active SI. Positive QBS and HLA-B27 tests were the best combination of screening tests with 82% predictability of inflammatory SI in whites, and QBS alone had an 80% predictability in black patients. However, MRI, which had 100% predictability, was the best single test for confirming active inflammatory SI.
1993[An autopsied case of intravascular malignant lymphomatosis with paraparesis, that presented a leukoencephalopathy-like image after spinal cord biopsy].Rinsho ShinkeigakuA 54-year-old woman was hospitalized because of paraparesis, sensory disturbance of the lower extremities, and dysuria. Laboratory data included an erythrocyte sedimentation rate (ESR) of 16 mm/h and lactate dehydrogenase (LDH) level of 459 IU/l. Myelogram showed an enlarged spinal cord at the L1 level, and spinal MRI revealed a high signal area on T2-weighted images. Spinal cord biopsy by thoraco-lumbar laminectomy showed thickening of the pia mater and neovascularization, but no malignant cells. Immediately after the operation, the patient displayed progressive mental deterioration. Cranial MRI showed widespread high signal areas in the cerebral white matter on T2-weighted images which resembled those of leukoencephalopathy. Steroid therapy was tried but was ineffective. Ten months after the onset of symptoms, a brief period of regression of both clinical symptoms and MRI appearances occurred following the administration of Inosiplex, subsequent progressive deterioration led to death 14 months after the onset of symptoms. LDH, C-reactive protein (CRP), and cerebrospinal fluid (CSF) protein were all elevated during the deterioration of her general status. Postmortem examination revealed a large tumor mass of the left adrenal gland which extended to the Th12, L1, and L2 vertebrae and remarkable brain edema. Microscopic mononuclear tumor cells were widespread but confined to the lumens of small vessels of the brain, spinal cord, spinal root and right adrenal gland, almost as if they were occluded. Cerebral white matter presented widespread multiple small infarcts and extensive myelin thinning. In addition to the left adrenal gland, interstitial invasions of tumor cells were discovered in the kidneys, iliopsoas muscles, oviducts, myocardium, lymph nodes, and thyroid gland.(ABSTRACT TRUNCATED AT 250 WORDS)
1991[Clinical and pathological study of 34 patients with isolation of methicillin-resistant Staphylococcus aureus in stool culture].Kansenshogaku ZasshiClinical and pathological findings of 34 patients with isolation of methicillin-resistant Staphylococcus aureus (MRSA) from stools during the past one and half a year were studied. Twenty-three patients (68%) had internal diseases and the remaining were postoperative patients (32%). Thirty-three patients (97%) had diarrhea, and properties of the stools were watery in twenty-four and mushy in nine. The degrees of fever, leukocytosis and increase of serum C-reactive protein as inflammatory signs were various, and these had no relation with severity of diarrhea. Diarrhea preceded MRSA infection of organs except for the digestive tract in 7 patients (21%) and appeared alone in 14 patients (41%). These results indicate that closed observation of the stool was very important for early diagnosis of MRSA enterocolitis. C. difficile were isolated in 17 patients (50%) and there were many patients whom C. difficile took part in diarrhea. We should take notice of this organism on stool culture and therapy of diarrhea. Twenty-seven patients (79%) improved and 7 patients (21%) died. Three patients who did had MRSA enterocolitis as one of the cause of death. This shows that early diagnosis and therapy are important and fundamental therapy are the attempt of improvement of the general condition and appropriate use of antibiotics. Pathologically most the common finding was edema of the colon, which was found in 4 of five autopsied patients, and specific findings were not observed. As other findings, edema and bleeding of ileum and multiple erosion of the colon were found in one, bleeding of the colon in one, and neutrophil infiltration and pseudomembrane of the colon in one with isolation of C. difficile.
1991Serum-erythropoietin concentration during acute cardiogenic pulmonary edema.AngiologyReduced oxygen tension is regarded as the primary physiologic signal for the production of erythropoietin (EPO). There is little information available about early changes of EPO production in man due to severe hypoxia. The purpose of the present study was to examine the time course of EPO in serum of patients with acute cardiogenic pulmonary edema (ACPE). In 29 patients (seventy-five +/- six years, mean age +/- SEM) who were hospitalized within two hours after onset of symptoms of ACPE, serum EPO concentrations were monitored for up to seventy-two hours. At the moment of admission all patients showed significantly increased EPO concentrations of 121 +/- 64 mU/mL (mean +/- SEM) compared with a healthy population (15-35 mU/mL). Twenty-three patients who recovered within thirty minutes (group A) exhibited a quick return of their EPO serum levels to normal. The remaining 6 patients (group B) had a protracted clinical course and their EPO concentration showed a further increase up to the end of the observation period. The comparative monitoring of concentrations of alpha-1-proteinase inhibitor, antithrombin III, C-reactive protein, fibronectin, hapotoglobin, and transerrin in serum and plasma revealed no significant changes. Thus a major contribution of fluid shifts into or from the intravascular compartment to the observed changes in EPO concentration seems to be unlikely. The data suggest that the production and release of EPO in the kidneys due to altered oxygen delivery is a fast-responding mechanism.
1991[A case of pustulotic arthro-osteitis with secondary amyloidosis].RyumachiA 63-year-old man with a history of Pustulosis Palmaris et Plantaris since 1960 was suffered from lumbago and anterior chest pain in 1973. Chest X-ray film showed inter-sterno-costo-clavicular ossification. Spondylodiscitis, Syndesmophyte of lumbal spine, Sacro-iliitis were seen by abdominal X-ray film. He was admitted to near hospital with generalized edema and urinary protein (10-20 g/day) in April 1986. Laboratory studies showed hypoproteinemia, positive C-reactive protein, high serum amyloid A protein(240 ng/100 microliters) and negative HL-A B27. He was diagnosed Pustulotic arthro-osteitis and Secondary Amyloidosis by renal biopsy and rectal biopsy in 1987. He was treated with high-dose oral prednisolone(60 mg/day)and dimethyl sulfoxide. After treatment, Edema and Nephrose improved. Increasement of renal function was not observed.
1990Successful therapy of meningococcal sepsis in acute disseminated lupus erythematosus with plasmapheresis, immunosuppression, and antibiotics.Klin WochenschrA 17-year-old female with a 5-year history of disseminated lupus erythematosus has remained without immunosuppressive therapy for the last 3 years. She was admitted to the hospital for acute abdominal pain, generalized edema, and rapidly developing dyspnea and somnolence. Although all symptoms were consistent with active SLE, septicemia was suspected because of leukocytosis (20,000/microliters), greatly elevated C-reactive protein (45 mg/dl), and normal complement values (C3 0.74 g/l, C4 0.21 g/l). Directly after bacterial blood cultures were prepared, a combined treatment was instituted consisting of plasmapheresis (3 x 2.1 l against fresh frozen plasma), antibiotics, prednisolone, and cyclophosphamide following the last plasmapheresis. Within three days cerebral function returned to normal, edema improved, and CRP fell to 0.5 mg/dl. The blood cultures and pericardial effusion displayed meningococcal colonies.
1990[A controlled study on edema in elderly inpatients].Nihon Ronen Igakkai ZasshiThe clinical background relating to edema in elderly inpatients was investigated, in terms of various items in elderly (aged greater than or equal to 65) cases with edema (n = 96) and without edema (controls, n = 95). Both groups were matched for sex, age, and underlying diseases. As compared with the control patients, the patients with edema had longer hospital stays with more disabled status, and showed less activity of daily living (ADL). The rates of bed-restricted patients, dementia patients, and patients with decubitus, muscle atrophy, or incontinence were found to be significantly higher in the patients with edema. The measurement of biochemical parameters revealed that the patients with edema had significantly lower levels of serum albumin, Na, Cl, creatinine, and uric acid, in contrast to higher levels of C-reactive protein. According to the classification of the assumed causes of edema, we divided the patients with edema into five groups; group 1 (n = 33): edema associated with immobilization, group 2 (n = 18): edema due to heart failure, group 3 (n = 15): edema on paretic limbs, group 4 (n = 6): edema due to hypoproteinemia, group 5 (n = 5): edema associated with liver cirrhosis. Both group 1 and group 4 patients had lower levels of hemoglobin and albumin, whereas group 3 patients had higher scores of ADL, higher blood pressure, and higher levels of hemoglobin and albumin. These results suggest that immobilization and restriction in bed, as well as malnutrition, were important factors in causing edema in elderly inpatients.
1988Myocarditis with multinucleated giant cells detected in biopsy specimens.Clin CardiolA 42-year-old woman was transferred to our hospital for evaluation of bradycardia with a complete atrioventricular block. Her pulse was 41 regular beats/min with blood pressure 166/92 mmHg. There were no skin lesions, edema, or lymphadenopathy. The white blood cell count was 6300/mm3. The serum glutamic oxaloacetic transaminase was 21 IU and creatine phosphokinase was 34 IU. C-reactive protein was negative. The level of serum angiotensin converting enzyme was slightly increased at 25.8 IU/l/37.0 degrees C (normal range: 7-24.0). Chest radiography showed congestive heart failure with a cardiothoracic ratio of 54%. There was no bilateral lymphadenopathy or fibrous changes during her clinical course. The coronary arteries were completely normal angiographically. Left ventriculograms revealed slight hypokinesis and dilatation (end-diastolic volume index of 112 ml/m2, ejection fraction of 53%). Left ventricular end-diastolic pressure was slightly abnormal at 16 mmHg. Two right and two left ventricular endomyocardial biopsies were performed. Right ventricular biopsy demonstrated edematous tissue and a slight mononuclear cell infiltration with little fibrosis. Left ventricular specimens showed an extensive area of fibrosis, with large, multinucleated giant cells with an asteroid body and chronic inflammation without epithelioid cells. The less affected areas of another specimen showed mild interstitial fibrosis and degenerative myocytes with vacuolation, and some multinucleated myocytes without an asteroid body were present. This case was diagnosed as cardiac sarcoidosis rather than idiopathic giant cell myocarditis. The patient has been implanted with a permanent pacemaker.(ABSTRACT TRUNCATED AT 250 WORDS)
1988Five patients with painless thyroiditis simultaneously developed in a nursery school.Endocrinol JpnPainless (silent) thyroiditis (PT) occurred simultaneously in 1 male and 4 females aged 21 to 52 years working at a nursery school. Clinical symptoms did not include goiter, or pain or tenderness of the neck in any of the patients but were characterized by edema of the lower legs as well as palpitation and loss of body weight as observed in subacute thyroiditis. General blood analysis showed that all patients were negative for C-reactive protein (CRP) and 3 had mild impairment of liver function. Examination of thyroid function suggested transient thyrotoxicosis accompanied by a marked reduction in radioactive iodine uptake (RAIU), but antithyroglobulin hemagglutination antibody (TGHA) and antithyroid microsomal hemagglutination antibody (MCHA) were negative in all patients. Examination of various viral antibodies showed no significant changes in their titers. Thyrotoxicosis was transient and disappeared without treatment or by glucocorticoid administration. Our results suggested that PT observed in this study was caused by some environmental factor. The possibility of an unidentified virus as a factor cannot be ruled out.
1987[Topical use of Rheumon-Gel in the combined treatment of patients with rheumatoid arthritis].Ter ArkhRheumon-Gel was used for therapy of 51 patients with rheumatoid arthritis. It has been shown that the drug has a marked antiinflammatory and analgesic action, a positive effect on a number of subjective (pain in the joints and constrained movements in the morning), objective (body temperature, edema and joint function), and laboratory (leucocyte count, ESR, C-reactive protein, titer of antistreptolysin-O and antistreptohyaluronidase) indices and therefore it can be recommended for multimodality therapy of rheumatic patients, particularly of those with rheumatoid arthritis combined with G. I. tract diseases when the use of most of the antirheumatic drugs is counterindicated.