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41.
Clay Jean-Charles Chrystèle Rubod Mathias Brieu Malik Boukerrou Jean Fasel Michel Cosson 《International urogynecology journal》2010,21(12):1535-1538
Introduction and hypothesis
Our aim is to characterize prolapsed and non-prolapsed vaginal tissue, and thus offer a better understanding of the genital prolapse physiopathology and an improvement of surgical treatments. 相似文献42.
Arnaud Avril Jean-Nicolas Tournier Jean-Charles Paucod Bndicte Fournes Philippe Thullier Thibaut Pelat 《Toxins》2022,14(3)
Anthrax is an acute disease caused by the bacterium Bacillus anthracis, and is a potential biowarfare/bioterrorist agent. Its pulmonary form, caused by inhalation of the spores, is highly lethal and is mainly related to injury caused by the toxins secretion. Antibodies neutralizing the toxins of B. anthracis are regarded as promising therapeutic drugs, and two are already approved by the Federal Drug Administration. We developed a recombinant human-like humanized antibody, 35PA83 6.20, that binds the protective antigen and that neutralized anthrax toxins in-vivo in White New Zealand rabbits infected with the lethal 9602 strain by intranasal route. Considering these promising results, the preclinical and clinical phase one development was funded and a program was started. Unfortunately, after 5 years, the preclinical development was cancelled due to industrial and scientific issues. This shutdown underlined the difficulty particularly, but not only, for an academic laboratory to proceed to clinical development, despite the drug candidate being promising. Here, we review our strategy and some preliminary results, and we discuss the issues that led to the no-go decision of the pre-clinical development of 35PA83 6.20 mAb. Our review provides general information to the laboratories planning a (pre-)clinical development. 相似文献
43.
Tremblay AJ Lamarche B Ruel I Hogue JC Bergeron J Gagné C Couture P 《Atherosclerosis》2004,172(2):367-373
Increasing evidence suggests that remnants of chylomicrons and very low density lipoprotein (VLDL) also known as triglyceride-rich lipoproteins (TRL) are directly related to the pathogenesis of atherosclerosis. While studies in animals suggest that low density lipoprotein (LDL) receptor deficiency delays clearance of chylomicron remnants, human data supporting this hypothesis are conflicting. The objective of this study was to compare the fractional catabolic rate (FCR) and production rate (PR) of TRL apolipoprotein B48, the principal structural protein of intestinally derived chylomicron remnants, between familial hypercholesterolemic (FH) heterozygotes and non-FH controls. This was achieved by examining the kinetics of TRL apo B48 labelled with a stable isotope (L-(5,5,5-D3)leucine) in five normolipidemic males (age: 24.7 +/- 1.3 years; body mass index (BMI): 23.9 +/- 1.4 kg/m2) and six genetically defined FH heterozygous males (age: 29.7 +/- 9.9 years; (BMI): 22.0 +/- 4.3 kg/m2) carrying the same null LDL receptor gene mutation. All participants were apo E3 homozygotes. During the kinetic study, the subjects consumed 1/30 of their daily food intake every 30 min over a 15 h period. No significant difference was observed between FH heterozygotes and controls for FCR of TRL apo B48 (7.9 +/- 2.1 versus 7.9 +/- 2.6 pools per day, P = 0.99) while the TRL apo B48 pool size (10.5 +/- 5.4 versus 5.7 +/- 2.4 mg, P = 0.03) and PR (1.1 +/- 0.3 versus 0.6 +/- 0.3 mg kg(-1) per day, P = 0.02) were significantly higher among FH than in controls. In conclusion, this study shows no evidence for reduced plasma apo B48 catabolism in patients with heterozygous FH carrying the same null LDL receptor gene mutation and suggests that the plasma levels of intestinally derived TRL are elevated in FH due to an increased production rate. 相似文献
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Frémeaux-Bacchi V Guinnepain MT Cacoub P Dragon-Durey MA Mouthon L Blouin J Cherin P Laurent J Piette JC Fridman WH Weiss L Kazatchkine MO 《The American journal of medicine》2002,113(3):194-199
PURPOSE: Acquired angioedema type 1 is characterized by a C1 inhibitor deficiency in patients with lymphoproliferative disorders, whereas acquired angioedema type 2 is characterized by anti-C1 inhibitor antibodies, and has not been thought to be associated with lymphoproliferative disease. We studied the clinical features, complement profiles, and associated diseases in 19 new patients with diagnosed acquired angioedema type 2. SUBJECTS AND METHODS: Plasma concentrations and functional activity of complement components were measured by conventional techniques. Functional C1 inhibitor activity was assessed by a chromogenic assay. Autoantibodies to C1 inhibitor were detected using an enzyme-linked immunosorbent assay. RESULTS: The 11 men and 8 women (median age, 60 years) presented with recurrent attacks of angioedema. All patients had detectable anti-C1 inhibitor antibodies in serum. A monoclonal gammopathy was detected in 12 patients (63%) at the time of diagnosis, 11 of whom had an immunoglobulin peak of the same heavy- and light-chain isotypes as the acquired anti-C1 inhibitor antibody. Three of these 12 patients developed a malignant lymphoproliferative disease. CONCLUSION: As with type 1 disease, a large proportion of patients with acquired angioedema type 2 have a lymphoproliferative disorder. 相似文献
46.
Shepherd J Barter P Carmena R Deedwania P Fruchart JC Haffner S Hsia J Breazna A LaRosa J Grundy S Waters D 《Diabetes care》2006,29(6):1220-1226
OBJECTIVE: The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastatin 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable coronary heart disease (CHD). The objective of our study was to investigate whether similar benefits of high-dose intensive atorvastatin therapy can be achieved in patients with CHD and diabetes. RESEARCH DESIGN AND METHODS: A total of 1,501 patients with diabetes and CHD, with LDL cholesterol levels of <130 mg/dl, were randomized to double-blind therapy with either atorvastatin 10 (n = 753) or 80 (n = 748) mg/day. Patients were followed for a median of 4.9 years. The primary end point was the time to first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke. RESULTS: End-of-treatment mean LDL cholesterol levels were 98.6 mg/dl with atorvastatin 10 mg and 77.0 mg/dl with atorvastatin 80 mg. A primary event occurred in 135 patients (17.9%) receiving atorvastatin 10 mg, compared with 103 patients (13.8%) receiving atorvastatin 80 mg (hazard ratio 0.75 [95% CI 0.58-0.97], P = 0.026). Significant differences between the groups in favor of atorvastatin 80 mg were also observed for time to cerebrovascular event (0.69 [0.48-0.98], P = 0.037) and any cardiovascular event (0.85 [0.73-1.00], P = 0.044). There were no significant differences between the treatment groups in the rates of treatment-related adverse events and persistent elevations in liver enzymes. CONCLUSIONS: Among patients with clinically evident CHD and diabetes, intensive therapy with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events by 25% compared with atorvastatin 10 mg. 相似文献
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48.
Thierry Bège Ariadne Desjeux Benjamin Coquet-Reinier Stéphane V. Berdah Jean-Charles Grimaud Christian Brunet 《Journal of gastrointestinal surgery》2011,15(8):1486-1487
Introduction
Rapunzel syndrome is a rare entity comprising of a large gastroduodenal trichobezoar due to trichotillomania. Its treatment is often surgical. 相似文献49.
Hoi MT Desjeux A Bach TT Barthet M Grimaud JC 《Gastroentérologie clinique et biologique》2002,26(11):968-972
AIM: Ascariasis is the most widespread helminthiasis in the world. Biliary and pancreatic involvement, frequently encountered in endemic areas, is a serious public health problem. Surgical management is often required. The purpose of our work was to assess the feasibility of emergency endoscopic treatment of biliary and pancreatic ascariasis in the Viet Duc hospital (Hanoi, Vietnam), and to evaluate outcome. METHODS: A prospective study conducted over a 3-year period included 91 patients with biliary and pancreatic ascariasis. Diagnosis was based on clinical findings and abdominal ultrasound and was confirmed by endoscopic procedures. RESULTS: The 91 patients, 21 males and 70 females, mean age 41 +/- 17 years, underwent endoscopic procedures to retrieve the worm. The procedure was successful in 89 patients (97.8%). Mild pancreatitis occurred in four patients who underwent biliary sphincterotomy. The mean hospital stay was 3.1 days. CONCLUSION: Endoscopic management of ascariasis is feasible, with a very low morbidity and a high rate of success. With this treatment, hospital stay is greatly shortened. 相似文献
50.