HLA-DPB1 gene polymorphism and multiple sclerosis: a large case-control study in the southwest of France

The polymorphism at the HLA-DPB1 locus has been characterized in a large number of patients with multiple sclerosis (n = 112) and in healthy controls (n = 115). Both patients and controls lived in the southwest of France (in the Pyrénées Atlantiques) and had similar ethnic background. The typing procedure involved the selective amplification of the second exon of the DPB1 locus by polymerase chain reaction, followed by hybridization of the amplified DNA with 14 sequence-specific oligonucleotide probes. Individual alleles were identified by the pattern of hybridization of the different probes. The distribution of the DPB1 alleles was not significantly different in multiple sclerosis patients and controls (p = 0.11). This does not corroborate the reported association of multiple sclerosis with the primed lymphocyte typing (PLT)-defined DPw4 specificity and is not in favour of a role played by polymorphic residues of the DP molecule in susceptibility to multiple sclerosis.     

Standardized quick en bloc technique for procurement of cadaveric liver grafts for pediatric liver transplantation

This paper describes a quick procedure for cadaveric liver graft retrieval during multiple organ harvesting. The technique is based on minimal preliminary dissection, absence of in situ direct portal perfusion, and en bloc removal of the liver and pancreas, with an aortic patch encompassing the coeliac trunk and superior mesenteric artery. The results of 110 pediatric liver transplantations with 109 organs harvested using this technique are reported. There were no graft harvesting injuries. The liver graft primary nonfunction rate was 4.5% (5/110). The 3-month retransplantation rate was 10%. The actual patient survival rates were 93% at 3 months and 90% at 1 year; actual graft survival rates were 85.5% and 78%, respectively. The technique described was at least as safe as conventional procedures. A major advantage of the procedure is its flexibility, which allows for the easily combined procurement of other organs (whole pancreas and intestine).     

Major vascular injuries during gynecologic laparoscopy

Background:This study was undertaken to report our experience with major vascular injuries in gynecologic laparoscopy in order to specify the circumstances under which they occurred, the means of diagnosis, the risk factors, and the means for prevention.Study Design:Retrospective case review study.Results:Seventeen patients with 21 major vascular injuries were identified. The average age of the patients was 33.8 ± 11.6 years, and the mean body index mass was 21.6 ± 3.08 kg/m². Three of four of the accidents occurred during the set-up phase of laparoscopy (13 cases; 76.5%), and in 4 cases (23.5%) the accident occurred during the laparoscopic surgery procedure. Eleven (84.6%) of the complications occurring during the set-up phase were secondary to insertion of the umbilical trocar and 2 (15.4%) to insertion of the needle used to create the pneumoperitoneum (P-needle). Half (6 cases; 54.5%) of the major vascular injuries secondary to insertion of the umbilical trocar were observed when reusable trocars were used. In every case, the diagnosis was made during the operation. Two patients died, and two others presented a serious complication (phlebitis; acute ischemia requiring reoperation).Conclusions:Major vascular injuries are rare but serious complications of laparoscopic surgery. Prevention of these accidents relies on the surgeon’s experience and scrupulous respect of the safety rules. In the vast majority of cases, it is necessary to convert to laparotomy immediately, calling in a vascular surgeon.     

A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer

BACKGROUND: There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). METHODS: This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. RESULTS: Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1-2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52-665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. CONCLUSION: Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors.     

Saturable rate of cefatrizine absorption after oral administration to humans

This study examined the absorption kinetics of cefatrizine, an amino--lactam antibiotic, after oral administration of a single 500-mg dose to 12 healthy volunteers. Plasma concentrations were determined by high performance liquid chromatography. The plots of the percentage of drug unabsorbed and the apparent rate of cefatrizine absorption as a function of time showed, first, a delay and, then, an almost constant rate of absorption with a tendency to move toward first-order kinetics at the end of the process. Three compartmental models incorporating a lag time and first-order elimination kinetics, but differing in their input rate, were used for analysis of the time course of cefatrizine plasma concentrations. The model with first-order absorption kinetics was clearly inadequate. The results were improved with the model for which the rate of absorption is constant, but a model incorporating saturable absorption kinetics of the Michaelis-Menten type improved the fit further. This last model was statistically superior to the constant-rate input model in 6 out of 12 subjects, according to the likelihood-ratio method. Because of the innovative feature of the model incorporating the Michaelis-Menten equation, simulations of the effect of altering the model parameters and the dose administered on the concentration-time profile, were performed. Different hypotheses which might explain why cefatrizine absorption kinetics fits the Michaelis-Menten equation were examined. The observation of saturable absorption kinetics is consistent with a carrier-mediated transport previously reported to occur in the gastrointestinal tract of rats.     

Risk factors for pelvic organ prolapse repair after hysterectomy

OBJECTIVE: To estimate the incidence and identify the risk factors for pelvic organ prolapse repair after hysterectomy. METHODS: We conducted a case-control study. We identified 6,214 women who underwent hysterectomy in our gynecology department from 1982 to 2002. Cases (n=114) were women who required pelvic organ prolapse surgery after hysterectomy from January 1982 through December 2005. Controls (n=236) were women randomly selected from the same cohort who did not require pelvic organ surgery during the same period. We performed a univariable and a multivariable analysis among 104 cases and 190 controls to identify the variables associated with prolapse repair after hysterectomy. RESULTS: The incidence of pelvic organ prolapse that required surgical correction after hysterectomy was 1.3 per 1,000 women-years. The risk of prolapse repair was 4.7 times higher in women whose initial hysterectomy was indicated by prolapse and 8.0 times higher if preoperative prolapse grade 2 or more was present. Risk factors included preoperative prolapse grade 2 or more (adjusted odds ratio [OR] 12.6, 95% confidence interval [CI] 4.6-34.7), previous pelvic organ prolapse or urinary incontinence surgery (adjusted OR 7.9, 95% CI 1.3-48.2), history of vaginal delivery (adjusted OR 5.0, 95% CI 1.3-19.7), and sexual activity (adjusted OR 6.2, 95% CI 2.7-14.5). Vaginal hysterectomy was not a risk factor when preoperative prolapse was taken into account (adjusted OR 0.7, 95% CI 0.4-1.1). CONCLUSION: Preoperative pelvic organ prolapse and other factors related to pelvic floor weakness were significantly associated with subsequent pelvic floor repair after hysterectomy. Vaginal hysterectomy was not a risk factor. LEVEL OF EVIDENCE: II.