Facteurs pronostiques en insémination avec sperme de donneur : suivi rétrospectif d’une cohorte de 188 patientes

ObjectivesImproving our practice by a constant evaluation is essential in the field of donor semen insemination (DI). Our center examined the prognosis factors for DI success in order to standardize patient treatment options.Patients and methodsWe retrospectively analysed all couples referred for DI from January 2000 till December 2010.ResultsWe analysed 551 cycles among 188 patients. Pregnancy rate by stimulation cycle was 19,8% with birth rate of 16.7%. The rate of pregnancy was improved till the fourth trial then plateau. On a patient-based analysis, success factors were age (P = 0.04), previous successful DSI (P = 0.02), and no previous failure of an ICSI-C (P = 0.035). On a cycle-based analysis, success factors were the number of follicles greater than 15 mm (P = 0.04) and than 18 mm (P = 0.001). The percentage of 68.1 patients obtained a child by IVF-D after a failed DI.ConclusionThere are two predictive factors for DI success: the age of the patient and the number of mature follicles. It seems accurate to referred patients to IVF-D after four unsuccessful cycles of DSI. This recommendation may be adapted according to patient's age and hormonal evaluation.     

Targeting the “Cytokine Storm” for Therapeutic Benefit

Inflammation is the body''s first line of defense against infection or injury, responding to challenges by activating innate and adaptive responses. Microbes have evolved a diverse range of strategies to avoid triggering inflammatory responses. However, some pathogens, such as the influenza virus and the Gram-negative bacterium Francisella tularensis, do trigger life-threatening “cytokine storms” in the host which can result in significant pathology and ultimately death. For these diseases, it has been proposed that downregulating inflammatory immune responses may improve outcome. We review some of the current candidates for treatment of cytokine storms which may prove useful in the clinic in the future and compare them to more traditional therapeutic candidates that target the pathogen rather than the host response.     

Stability of monoclonal antibodies after simulated subcutaneous administration

Changes in the environment from the drug product to the human physiology might lead to physical and/or chemical modifications of the protein drug, such as in vivo aggregation and fragmentation. Although subcutaneous (SC) injection is a common route of administration for therapeutic proteins, knowledge on in vivo stability in the SC tissue is limited. In this study, we developed a physiologic in vitro model simulating the SC environment in patients. We assessed the stability of two monoclonal antibodies (mAbs) in four different protein-free fluids under physiologic conditions. We monitored protein stability over two weeks using a range of analytical methods, in analogy to testing purposes of a drug product. Both mAbs showed an increase of protein aggregates, fragments, and acidic species. mAb1 was consistently more stable in this in vitro model than mAb2, highlighting the importance of comparing the stability of different mAbs under physiologic conditions. Throughout the study, both mAbs were substantially less stable in bicarbonate buffers as compared to phosphate-buffered saline. In summary, our developed model was able to differentiate stability between molecules. Bicarbonate buffers were more suitable compared to phosphate-buffered saline in regards to simulating the in vivo conditions and evaluating protein liabilities.     

Treating Fragile X syndrome with the diuretic bumetanide: a case report

We report that daily administration of the diuretic NKCC1 chloride co‐transporter, bumetanide, reduces the severity of autism in a 10‐year‐old Fragile X boy using CARS, ADOS, ABC, RDEG and RRB before and after treatment. In keeping with extensive clinical use of this diuretic, the only side effect was a small hypokalaemia. A double‐blind clinical trial is warranted to test the efficacy of bumetanide in FRX. Conclusion: This single case report showed an improvement of the scores of each test used after 3 months of treatment. Double‐blind clinical trials are warranted to test the efficacy of bumetanide in FRX.     

Les médecins traitants devant le défi du dépistage et de la prise en charge de l’endométriose : résultats d’une enquête

ObjectiveTo evaluate the knowledge of general practitioners concerning the endometriosis diagnostic and care.Population and methodsSurvey enrolling 100 general practitioners of the 76th Seine Maritime French department (region of Upper Normandy) who usually perform gynaecological follow up, asked to answer an irreversible 36 item step-by-step questionnaire.ResultsAmong them, 44% perform more than one gynaecological consultation each week. They were 63% to feel ill at ease in the diagnosis and follow up of women presenting with endometriosis. One half of physicians could not cite three main symptoms of the disease out of dysmenorrhea, dyspareunia, chronic pelvic pain and infertility. Only 38% of general practitioners perform a clinical gynaecological examination when they suspect the endometriosis, and 28% of them recommended MRI to confirm the diagnosis. They are 24% to refer the patient without delay, but only 52% to the universitary hospital, which is the tertiary regional referral center, while 68% of them refer to a fellow practicing in a private facility. They were 64% to believe that therapeutic amenorrhea is on the bottom of the medical therapy. General practitioners were more likely to accurately answer the questionnaire when they attended gynaecological advanced courses during previous 5 years and when they followed up more than three patients previously managed for endometriosis.Discussion and conclusionGeneral practitioners’ knowledge about endometriosis is limited, with possible direct consequences on the delay of the diagnosis. The attendance of gynaecological advanced courses and the exchange of information between gynaecologic surgeons and general practitioners who follow up the patients appear to be two-way to improve the accuracy of the answers to the questionnaire.