Infliximab plus azathioprine for steroid-dependent Crohn's disease patients: a randomized placebo-controlled trial. |
Thu, Jul 22,2010 |
BACKGROUND & AIMS: The aim of this study was to evaluate the usefulness of short-term infliximab combined with azathioprine (AZA) or 6-mercaptopurine (6-MP) in steroid-dependent Crohn's disease patients. METHODS: Patients with active disease despite prednisone given for more than 6 months were eligible and were stratified as follows: the failure stratum consisted of patients receiving AZA/6-MP at a stable dose for more than 6 months, and the naive stratum consisted of patients not treated previously with AZA/6-MP. Patients were randomized to infliximab 5 mg/kg or placebo at weeks 0, 2, and 6. All patients were treated with AZA/6-MP maintained at a stable dose throughout the 52 weeks of the study. The primary end point was remission off steroids at week 24. RESULTS: Among the 113 enrolled patients (55 in the failure stratum), 57 were assigned to infliximab. At week 24, the success rate (intent-to-treat analysis) was higher in the infliximab group than in the placebo group (57% vs 29%; P = .003); at weeks 12 and 52, the corresponding rates were 75% vs 38% (P < .001) and 40% vs 22% (P = .04), respectively. In each stratum, the success rate was significantly higher in the infliximab group at weeks 12 and 24, and a trend was found at week 52. In the failure stratum, only 27% of the patients in the infliximab group were still in remission off steroids, compared with 52% in the naive stratum. Steroid resistance was less common and the cumulative dose of prednisone was lower in the infliximab group. CONCLUSIONS: Infliximab plus AZA/6-MP is more effective than AZA/6-MP alone in steroid-dependent Crohn's disease patients.
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Marked efficacy of a therapeutic strategy associating prednisone and plasma exchange followed by rituximab in two patients with refractory myopathy associated with antibodies to the signal recognition particle (SRP). |
Thu, Jul 22,2010 |
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We report two patients with myopathy associated with anti-signal recognition particle Ab, refractory to conventional therapy, who were treated with prednisone and plasma exchange, followed by rituximab. A marked response was observed in both patients, with partial to complete recovery of muscle strength, which was sustained.
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A case of non-hodgkin's lymphoma of the ovary: usefulness of 18F-FDG PET for staging and assessment of the therapeutic response. |
Thu, Jul 22,2010 |
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Primary ovarian lymphoma as the initial manifestation is rare. A 27-year-old woman presented to our hospital with the symptoms of lower abdominal fullness and pollakisuria. CT scan and MRI revealed bilateral ovarian tumors, which showed heterogeneous masses. 18F-FDG PET revealed strong uptake by the abdominal masses, and the maximum standardized uptake value (SUVmax) was 12.5. Abnormal uptake was not shown by other regions. An exploratory laparotomy was performed. Histological findings revealed diffuse large B-cell lymphoma. The clinical stage was IV according to the Ann Arbor system. International prognostic index (IPI) was 3 (high-intermediate risk). Chemotherapy was administered consisting of three courses of an R-CHOP regimen, and 18F-FDG PET and CT scan revealed no signs of involvement 3 months after initiation of the chemotherapy. 18F-FDG PET was a useful method for staging and assessment of the therapeutic response in primary ovarian lymphoma.
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Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia. |
Thu, Jul 22,2010 |
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Activating mutations of the transmembrane receptor NOTCH1 are common in precursor T-cell lymphoblastic leukemia (T-ALL). We systematically analyzed the impact of activating NOTCH1 mutations on early treatment response and long-term outcome in 157 patients with T-ALL of the pediatric ALL-Berlin-Frankfurt-Munster (BFM) 2000 study. We confirm previous results that NOTCH1 mutations occur in more than 50% of T-ALL in children. In 82 patients (82/157; 52.2%), activating NOTCH1 mutations were identified either in the heterodimerization (55/82; 67.1%), in the PEST (13/82; 15.9%), or in both domains (14/82; 17.0%). The presence of NOTCH1 mutations was significantly correlated with a good prednisone response and favorable minimal residual disease (MRD) kinetics, which was independent from sex, age, white blood cell count, and T-cell immunophenotype at the time of diagnosis. Furthermore, activating NOTCH1 mutations specified a large subgroup of patients with an excellent prognosis. These findings indicate that in the context of the ALL-BFM 2000 treatment strategy, NOTCH1 mutations predict a more rapid early treatment response and a favorable long-term outcome in children with T-ALL.
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Enteropathy with loss of enteroendocrine and paneth cells in a patient with immune dysregulation: a case of adult autoimmune enteropathy. |
Thu, Jul 22,2010 |
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Autoimmune enteropathy (AIE) is a relatively rare condition found most frequently in children. It presents with persistent watery diarrhea and malabsorption and may require total parenteral nutrition for nutritional support. Rare cases have been reported in adults. On histology, the small intestinal villi are flattened but lack the intraepithelial lymphocytosis of celiac disease. In children and rarely in adults, some cases are linked to the IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked inheritance). We report a 21-year-old man who presented with chronic persistent diarrhea for 4 years. The duodenal biopsies showed villous blunting, chronic inflammation, and decreased to absent goblet cells, Paneth cells, and endocrine cells by histology and electron microscopy. These changes are consistent with an AIE with involvement of non-enterocyte populations. Pathologists must be aware of the possibility of AIE in adults and consider it in the differential diagnosis of duodenitis, intraepithelial lymphocytosis, and small bowel villous flattening.
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Guideline on the use of corticosteroids in Duchenne muscular dystrophy from paediatric neurologists, neurologists and rehabilitation physicians |
Thu, Jul 22,2010 |
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A guideline on the treatment of boys with muscular dystrophy with corticosteroids has been written and is available from the Dutch patients' organization. The guideline has been approved by the Dutch Societies of Neurology, Rehabilitation and Paediatrics. Based on the available literature the advice is to treat the boys with corticosteroids as soon as they become symptomatic. Prednisone is the drug ofchoice. The recommended dosage is 0.75 mg/kg body weight/day, every day or in a schedule of 10 days with treatment and 10 days without. From the initiation of the prednisone treatment dietary advice is given to control body weight. Monitoring for adverse effects takes place regularly.
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Clinical, etiological and progression factors of hearing in sudden deafness. |
Thu, Jul 22,2010 |
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Out of the many forms of therapy for sudden deafness, some require hospitalization and present significant risks. AIM: This prospective study analyzes etiology and evolution in cases of sudden deafness (SD) where outpatient oral treatment was used. STUDY DESIGN: Clinical with transversal cohort. MATERIAL AND METHOD: Forty cases of sudden hearing loss were followed for at least one year. All were submitted to initial clinical evaluation, auditory tests, routine blood analysis, and magnetic resonance imaging. All received initial treatment with pentoxifylline and prednisone. RESULTS: 45% (n=18) presented normal auditory thresholds, 40% (n=16) showed some improvement in hearing, 15% (n=6) maintained initial hearing level. Nine cases (22.5%) presented clinical conditions possibly implicated in hearing loss (viral infection, immunomediated hearing loss, vascular disorders, and so on); three (7.5%) had cerebellopontine tumors. Evolution of hearing in these 12 cases with presumed etiology presented no differences from hearing in the 28 cases without any known etiological factor. Clinical treatment within the first seven days was the only statistically significantly different condition in patients who improved hearing. CONCLUSIONS: An objective search for etiological bases should be conducted in any case of acute sensorineural hearing loss. The presence of cerebellopontine tumors in 7.5% of cases of SD, among other treated causes, justifies a thorough clinical investigation in these patients. Overall good evolution of hearing was observed in 67.5% of cases of SD, regardless of its etiology. Therapy within the first seven days of SD was significantly related to better outcomes in hearing.
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EBV B lymphoma cell lines from patients with post-transplant lymphoproliferative disease are resistant to TRAIL-induced apoptosis. |
Thu, Jul 22,2010 |
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Lymphomas associated with post-transplant lymphoproliferative disease (PTLD) represent a significant complication of immunosuppression in transplant recipients. In immunocompetent individuals, EBV-specific cytotoxic T lymphocytes (CTL) prevent the outgrowth of activated B lymphoblasts through apoptosis induction. Soluble versions of TNF-related apoptosis-inducing ligand/Apo2 ligand (TRAIL) can induce apoptosis in numerous tumor cell types. Given the therapeutic potential of TRAIL, we examined the sensitivity of EBV+ spontaneous lymphoblastoid cell lines (SLCL) derived from patients with PTLD to treatment with soluble TRAIL. Despite abundant expression of TRAIL receptors (TRAIL-R), resistance to TRAIL-induced apoptosis was observed in all SLCL examined. This resistance could not be overcome by concomitant treatment with several pharmacological agents. Unlike BJAB positive control cells, for each SLCL tested, cleavage and activation of caspase 8 was inhibited due to failed recruitment of FADD and caspase 8 to TRAIL receptors upon stimulation. Further indicative of a proximal defect, TRAIL receptor aggregation could not be detected on the cell surface of SLCL following ligand engagement. These results suggest that the use of TRAIL for eliminating PTLD-associated tumors may be of limited clinical utility, and illustrate another mechanism by which EBV+ B lymphoma cells can evade tumor surveillance at the level of death receptor signaling.
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Facial paralysis after temporal bone trauma |
Thu, Jul 22,2010 |
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OBJECTIVES: To evaluate functional outcome in 64 cases of facial paralysis following temporal bone fracture and discuss decisive arguments leading either to medical treatment or surgical management. METHODS: Sixty-four patients suffering from post-traumatic facial paralysis were managed between 1995 and 2003: 38 (59%) were given medical treatment and 26 (41%) underwent surgery. A combined middle fossa and transmastoid approach was mostly used (58%). Electrophysiological testing and CT scan results were the main points of the decision algorithm. RESULTS: Electroneuromyography seems to be the most accurate exploration for guiding treatment. Good results (grades I to II on the House and Brackmann scale) were obtained in 63% of cases after medical management and in 39% of cases after surgical treatment. Grades III or IV were obtained in 13% of medically-treated patients and 42% of surgically-treated patients. CONCLUSION: Management of facial paralysis following temporal bone fracture in accordance with electrophysiological testing (evoked EMG) together with CT scan findings enabled accurate indications for surgical treatment. A good grade I or II result can be expected after medical management. A grade III is at best reached after nerve anastomosis.
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Fibrillary glomerulonephritis in a patient with type 2 diabetes mellitus. |
Thu, Jul 22,2010 |
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We report a 62-year-old man with documented type 2 diabetes mellitus and hypertension, who presented with a rapid deterioration in renal function. The sudden decrease in renal function in this well-controlled diabetic patient prompted us to consider a nondiabetic and nonhypertensive cause. The urinary sediment showed a glomerular haematuria suggestive of glomerulonephritis. A diagnosis of fibrillary glomerulonephritis was made on renal biopsy. Fibrillary glomerulonephritis is a rarely diagnosed disease with clinical manifestations such as proteinuria, microscopic haematuria, nephrotic syndrome and impairment of renal function. A diagnosis of fibrillary glomerulonephritis can only be made by electronmicroscopy of the renal tissue. In this case report the spectrum of this disease is reviewed.
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