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Selected AbstractsAutoimmune hepatitis in the Indian subcontinent: 7 years experienceJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2001Rajesh Gupta Abstract Background: Autoimmune hepatitis (AIH) is presumed to be rare in India. The present prospective study was carried out to determine the prevalence, clinical, biochemical and histological profile of patients with AIH in India. Methods: Consecutive patients with chronic liver disease suspected to be AIH, were screened for antinuclear antibodies (ANA), antismooth muscle antibodies (ASMA), antimitochondrial antibody (AMA), and anti-liver kidney microsomal antibodies (anti-LKM-1). Serum protein electrophoresis and liver biopsy were done. Autoimmune hepatitis was diagnosed according to the International Autoimmune Hepatitis Group criteria. Results: Fifty of 1358 (3.43%) patients with chronic liver disease were diagnosed as autoimmune liver disease; 39 with AIH, two with overlap syndrome, five with primary sclerosing cholangitis, and four with primary biliary cirrhosis. Twenty-nine patients were categorized as definite AIH and 10 as probable AIH. Autoimmune hepatitis was common in females (males : females 1:3), with a mean age of 31 ± 17 years. Patients often presented with fatigue, jaundice and anorexia. Skin lesions (58%), joint symptoms (30%), and menstrual abnormalities (26%) were not uncommon. Mildly elevated alkaline phosphatase and hyper gamma globulinemia were seen in 78 and 91% patients, respectively. Eighty percent of patients were type I AIH, while 20% of cases remained unclassified. Histopathological changes included piecemeal necrosis (100%), plasma cell infiltration (91%), rosette formation (82%), and cirrhosis (76%). Overall mortality was 25% during a mean follow up of 15.7 ± 17.0 months. Conclusions: Our results clearly demonstrate that: (i) AIH is not uncommon in India; and (ii) while the profile and spectrum of AIH resembles that seen in the West, Indian patients present late, often in a cirrhotic state. [source] Concurrent de novo autoimmune hepatitis and recurrence of primary biliary cirrhosis post,liver transplantationLIVER TRANSPLANTATION, Issue 5 2001Chee Kiat Tan FRCP (Edin) Primary biliary cirrhosis (PBC) is well known to recur after liver transplantation (LT). The recurrence is usually subclinical and evident only on histological examination. Recently, a new entity of de novo autoimmune hepatitis (AIH) has emerged that occurs after LT in patients who underwent transplantation for diseases other than AIH. This new condition occurs more often in children; however, there was a recent report of the first 2 cases in adults who originally underwent LT for PBC. We report the first case of concurrent de novo AIH and recurrence of PBC documented on the liver biopsy of an adult patient who underwent LT for end-stage PBC. Unlike the earlier report of 2 adults, our patient manifested an antinuclear antibody titer of more than 1/800 from a previously negative titer pre-LT, as well as fulfilled the International AIH Group criteria for a definite diagnosis of AIH. PBC recurrence was evidenced by typical florid duct lesion, antimitochondrial antibody titer increasing from 1/40 to greater than 1/800, and an elevated serum immunoglobulin M level. After the addition of azathioprine to baseline immunosuppression of tacrolimus and prednisolone, the patient responded rapidly, with complete normalization of liver test results. [source] Effectiveness of rituximab treatment in primary Sjögren's syndrome: A randomized, double-blind, placebo-controlled trial,ARTHRITIS & RHEUMATISM, Issue 4 2010J. M. Meijer Objective To study the efficacy and safety of B cell depletion with rituximab, a chimeric murine/human anti-CD20 monoclonal antibody, in patients with primary Sjögren's syndrome (SS) in a double-blind, randomized, placebo-controlled trial. Methods Patients with active primary SS, as determined by the revised American,European Consensus Group criteria, and a rate of stimulated whole saliva secretion of ,0.15 ml/minute were treated with either rituximab (1,000 mg) or placebo infusions on days 1 and 15. Patients were assigned randomly to a treatment group in a ratio of 2:1 (rituximab:placebo). Followup was conducted at 5, 12, 24, 36, and 48 weeks. The primary end point was the stimulated whole saliva flow rate, while secondary end points included functional, laboratory, and subjective variables. Results Thirty patients with primary SS (29 female) were randomly allocated to a treatment group. The mean ± SD age of the patients receiving rituximab was 43 ± 11 years and the disease duration was 63 ± 50 months, while patients in the placebo group were age 43 ± 17 years and had a disease duration of 67 ± 63 months. In the rituximab group, significant improvements, in terms of the mean change from baseline compared with that in the placebo group, were found for the primary end point of the stimulated whole saliva flow rate (P = 0.038 versus placebo) and also for various laboratory parameters (B cell and rheumatoid factor [RF] levels), subjective parameters (Multidimensional Fatigue Inventory [MFI] scores and visual analog scale [VAS] scores for sicca symptoms), and extraglandular manifestations. Moreover, in comparison with baseline values, rituximab treatment significantly improved the stimulated whole saliva flow rate (P = 0.004) and several other variables (e.g., B cell and RF levels, unstimulated whole saliva flow rate, lacrimal gland function on the lissamine green test, MFI scores, Short Form 36 health survey scores, and VAS scores for sicca symptoms). One patient in the rituximab group developed mild serum sickness,like disease. Conclusion These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS. [source] Chlamydiae as etiologic agents in chronic undifferentiated spondylarthritisARTHRITIS & RHEUMATISM, Issue 5 2009John D. Carter Objective The majority of patients with Chlamydia -induced reactive arthritis do not present with the classic triad of arthritis, conjunctivitis/iritis, and urethritis. Moreover, acute chlamydial infections are often asymptomatic. The aim of the present study was to assess the prevalence of synovial Chlamydia trachomatis and Chlamydia pneumoniae infections in patients with chronic undifferentiated spondylarthritis (uSpA). Methods Study patients met the European Spondylarthropathy Study Group criteria for SpA, without evidence of ankylosing spondylitis, psoriasis, inflammatory bowel disease, or preceding dysentery. Symptoms were present for ,6 months. Each patient underwent a synovial biopsy; tissue and concomitantly obtained peripheral blood mononuclear cells (PBMCs) were analyzed by polymerase chain reaction (PCR) for C trachomatis and C pneumoniae DNA. Other data collected on the day of the biopsy included standard demographic information and medical history, including any known history of C trachomatis or C pneumoniae. Physical examination (including joint count, evaluation for dactylitis and/or enthesitis, and skin examination) and HLA,B27 typing were performed. Synovial tissue (ST) samples from 167 patients with osteoarthritis (OA) were used as controls. Results Twenty-six patients met the entry criteria and underwent synovial biopsy (25 knee, 1 wrist). Sixteen of them (62%) were positive for C trachomatis and/or C pneumoniae DNA (10 for C trachomatis, 4 for C pneumoniae, and 2 for both). PCR analysis of ST revealed the presence of Chlamydia significantly more frequently in patients with uSpA than in OA controls (P < 0.0001). No specific clinical characteristics differentiated Chlamydia -positive from Chlamydia -negative patients. PBMCs from 4 of the 26 uSpA patients (15%) were positive for Chlamydia, and Chlamydia was found in ST from 2 of these 4 patients. No significant correlation between PCR positivity and HLA,B27 positivity was found. Conclusion The frequency of Chlamydia -positive ST samples, as determined by PCR, was found to be significantly higher in patients with uSpA than in patients with OA. Our results suggest that in many patients with uSpA, chlamydial infection, which is often occult, may be the cause. [source] Clinical and imaging efficacy of infliximab in HLA,B27,Positive patients with magnetic resonance imaging,determined early sacroiliitis,ARTHRITIS & RHEUMATISM, Issue 4 2009Nick Barkham Objective To evaluate the efficacy of infliximab in HLA,B27,positive patients with magnetic resonance imaging (MRI),determined early sacroiliitis, using both clinical and MRI assessments. Methods Forty patients with recent-onset inflammatory back pain, as assessed by the Calin criteria, HLA,B27 positivity, clinical disease activity as measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), pain and morning stiffness, and magnetic resonance imaging (MRI),determined sacroiliac joint bone edema were randomized in a double-blind manner to receive infliximab 5 mg/kg or placebo at 0, 2, 6, and 12 weeks. MRI scans were performed at baseline and 16 weeks and scored by 2 observers (blinded to both the order of the scans and to treatment group), using the Leeds scoring system. Clinical assessments included the BASDAI, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Ankylosing Spondylitis Quality of Life (ASQoL) instrument, the ASsessment in Ankylosing Spondylitis International Working Group criteria (ASAS) for improvement, and markers of inflammation. Results The mean reduction in the total MRI score from week 0 to week 16 was significantly greater in infliximab-treated patients compared with placebo-treated patients (P = 0.033). On average, significantly more lesions resolved in the infliximab group (P < 0.001), while significantly more new lesions developed in the placebo group (P = 0.004). Significantly greater improvement in the infliximab group versus the placebo group was also observed for changes from week 0 to week 16 in the BASDAI (P = 0.002), BASFI (P = 0.004), and ASQoL (P = 0.007) scores. Responses according to the ASAS criteria for 40% improvement, the ASAS criteria for 20% improvement in 5 of 6 domains, and ASAS partial remission were achieved by 61%, 44%, and 56% of infliximab-treated patients, respectively. Infliximab was well tolerated, and no serious adverse events were observed. Conclusion Infliximab was an effective therapy for early sacroiliitis, providing a reduction in disease activity by week 16. This study is the first to show that infliximab is effective for reducing clinical and imaging evidence of disease activity in patients with MRI-determined early axial spondylarthritis. [source] Sjögren's syndrome and localized nodular cutaneous amyloidosis: Coincidence or a distinct clinical entity?ARTHRITIS & RHEUMATISM, Issue 7 2008Jiska M. Meijer Objective To report 8 patients with Sjögren's syndrome (SS) and localized nodular cutaneous amyloidosis and to examine serologic and immunohistologic findings that may link the 2 diseases. Methods The databases for 3 amyloidosis centers were searched for patients with localized nodular cutaneous amyloidosis and SS. Eight patients with this combination were identified, and clinical, serologic, and histologic parameters were retrospectively evaluated. Results Among the 8 patients with a clinical diagnosis of SS, 6 fulfilled the American,European Consensus Group criteria for SS. All of the patients were women in whom SS had been diagnosed at a median age of 47 years (range 30,61 years) and amyloid had been diagnosed at a median age of 60 years (range 42,79 years). The presence of the immunoglobulin light chain type of amyloid (AL amyloid) was confirmed in 4 patients. In 3 of these 4 patients as well as 2 other patients, a light chain,restricted plasma cell population was observed near the amyloid deposits. Progression to systemic amyloidosis was not observed in any patient during a median followup of 3.5 years. Conclusion SS should be considered in patients with cutaneous amyloidosis. The combination of cutaneous amyloidosis and SS appears to be a distinct disease entity reflecting a particular and benign part of the polymorphic spectrum of lymphoproliferative diseases related to SS. [source] Evidence-Based Strategies for Reducing Cesarean Section Rates: A Meta-AnalysisBIRTH, Issue 1 2007Nils Chaillet PhD ABSTRACT: Background: Canada's cesarean section rate reached an all-time high of 22.5 percent of in-hospital deliveries in 2002 and was associated with potential maternal and neonatal complications. Clinical practice guidelines represent an appropriate mean for reducing cesarean section rates. The challenge now lies in implementing these guidelines. Objectives of this meta-analysis were to assess the effectiveness of interventions for reducing the cesarean section rate and to assess the impact of this reduction on maternal and perinatal mortality and morbidity. Methods: The Cochrane Library, EMBASE, and MEDLINE were consulted from January 1990 to June 2005. Additional studies were identified by screening reference lists from identified studies and expert suggestions. Studies involving rigorous evaluation of a strategy for reducing overall cesarean section rates were identified. Randomized controlled trials, controlled before-and-after studies, and interrupted time series studies were evaluated according to Effective Practice and Organisation of Care Group criteria. Results: Among the 10 included studies, a significant reduction of cesarean section rate was found by random meta-analysis (pooled RR = 0.81 [0.75, 0.87]). No evidence of publication bias was identified. Audit and feedback (pooled RR = 0.87 [0.81, 0.93]), quality improvement (pooled RR = 0.74 [0.70, 0.77]), and multifaceted strategies (pooled RR=0.73 [0.68, 0.79]) were effective for reducing the cesarean section rate. However, quality improvement based on active management of labor showed mixed effects. Design of studies showed a higher effect for noncontrolled studies than for controlled studies (pooled RR = 0.76 [0.72, 0.81] vs 0.92 [0.88, 0.96]). Studies including an identification of barriers to change were more effective than other interventions for reducing the cesarean section rate (pooled RR = 0.74 [0.71, 0.78] vs 0.88 [0.82, 0.94]). Among included studies, no significant differences were found for perinatal and neonatal mortality and perinatal and maternal morbidity with respect to the mode of delivery. Only 1 study showed a significant reduction of neonatal and perinatal mortality (p < 0.001). Conclusions: The cesarean section rate can be safely reduced by interventions that involve health workers in analyzing and modifying their practice. Our results suggest that multifaceted strategies, based on audit and detailed feedback, are advised to improve clinical practice and effectively reduce cesarean section rates. Moreover, these findings support the assumption that identification of barriers to change is a major key to success. (BIRTH 34:1 March 2007) [source] Efficacy of low-dose dexamethasone in castration-refractory prostate cancerBJU INTERNATIONAL, Issue 4 2008Ramachandran Venkitaraman OBJECTIVE To evaluate the prostate-specific antigen (PSA) response rate and duration of PSA response to dexamethasone in patients with castration-refractory prostate cancer (CRPC), as corticosteroids are frequently used as second-line hormonal treatment of CRPC and there is little published evidence concerning the efficacy of low-dose dexamethasone in this setting. PATIENTS AND METHODS In all, 102 patients with progressive CRPC received oral dexamethasone (0.5 mg daily) between January 2003 and October 2006. The median pretreatment PSA level was 83 ng/mL. The main endpoint was the PSA response rate according to the PSA Working Group criteria. RESULTS In all, 50 patients (49%) had a confirmed PSA response. The median (range) time to PSA progression for the entire cohort was 7.4 (1,28) months. In responders, the median duration of the PSA response was 11.6 (1,24) months. CONCLUSION Low-dose dexamethasone has significant activity in CRPC. Subject to validation with more clinically meaningful endpoints, dexamethasone could become the corticosteroid of choice in the management of CRPC, and its potential for use in combination with novel agents should be explored. [source] A non-randomised dose-escalating phase II study of thalidomide for the treatment of patients with low-risk myelodysplastic syndromes: the Thal-SMD-2000 trial of the Groupe Français des MyélodysplasiesBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2005Didier Bouscary Summary Patients (n = 47) with low-risk myelodysplastic syndrome were treated with thalidomide [200 mg/d, increased by 200 mg/d/4 weeks up to week 16]. Responses were evaluated according to the International Working Group criteria at week 16 for 39 patients who received at least 8 weeks of treatment. Twenty-three (59%) patients showed haematological improvement (HI): four major erythroid response (HI-EM), 15 minor erythroid response, six major neutrophil response, two major platelet response. Side effects caused 22/39 to stop thalidomide before week 16. Nine of 23 responders continued thalidomide after week 16 [19% of trial patients] with sustained response in eight of nine. Six reached week 56, including the four HI-EM patients [13% of trial patients]. Nineteen of 36 red blood cell transfusion-dependent patients (53%) showed erythroid response, but only four became transfusion-independent. Among the 23 responders, the median duration of response was 260 d (range 30,650). Responses were sustained in all patients except one, and were observed between week 4 and week 8 in 85% of patients, at doses ranging from 200 to 400 mg. Only two patients responded at 600 mg/d and none at 800 mg/d. No clinical characteristics of responding versus non-responding patients were identified. The erythroid response rate was identical in all cytogenetic subgroups, including 5q31.1 deletions. Pretreatment vascular endothelial growth factor levels were lower in responders compared with non-responders (P = 0·004). Microvessel density (MVD) increased and apoptosis decreased in four of six and in all six responders studied respectively whereas MVD and apoptosis were unchanged in three non-responders. [source] | ||||||||||