Migraine in women: the role of hormones and their impact on vascular diseases

Migraine is a predominantly female disorder. Menarche, menstruation, pregnancy, and menopause, and also the use of hormonal contraceptives and hormone replacement treatment may influence migraine occurrence. Migraine usually starts after menarche, occurs more frequently in the days just before or during menstruation, and ameliorates during pregnancy and menopause. Those variations are mediated by fluctuation of estrogen levels through their influence on cellular excitability or cerebral vasculature. Moreover, administration of exogenous hormones may cause worsening of migraine as may expose migrainous women to an increased risk of vascular disease. In fact, migraine with aura represents a risk factor for stroke, cardiac disease, and vascular mortality. Studies have shown that administration of combined oral contraceptives to migraineurs may further increase the risk for ischemic stroke. Consequently, in women suffering from migraine with aura caution should be deserved when prescribing combined oral contraceptives

Uterine perforation as a complication of surgical abortion causing small bowel obstruction: a review

OBJECTIVE: Small bowel obstruction after unrecognized or conservatively treated uterine perforation is extremely rare. It is a surgical emergency and the delay in diagnosis and treatment has deleterious consequences for the mother. The purpose of this study is to critically review the available literature and ascertain the level of evidence for the mechanisms, diagnosis and management of small bowel obstruction after uterine perforation due to surgical abortion. ----- METHODS: Systematic literature search was conducted in Pubmed (1946 to 2012) and Pubmedcentral (1900 to 2012) including all available English and French language fulltext articles. Three evaluators reviewed and selected all available case reports and case series. Search terms included small bowel obstruction, bowel obstruction, bowel incarceration, bowel entrapment, vaginal evisceration, uterine perforation, uterine rupture, and abortion. The exclusion criteria were (1) complex injuries where small bowel incarceration was present but with bleeding and/or bowel perforation as the leading symptomatology; (2) articles only numbering the patients without details on the topic. Analyses of incidence, risk factors, mechanisms of the disease, time of clinical presentation, diagnostic modalities, treatment, and maternal outcome were included. ----- RESULTS: Of the 73 articles screened 30 cases of small bowel obstruction were included in the review forming incidence, risk factors, and mechanisms of the disease, diagnosis, therapy, and maternal outcome. ----- CONCLUSIONS: A systematic review defined four mechanisms of small bowel obstruction after transvaginal instrumental uterine perforation with significant variations in clinical presentation and time of presentation. Duration of symptoms depend on the mechanism of small bowel obstruction. Vaginal evisceration is surgical emergency and treatment is mandatory without diagnostic workup. Survival rate during last century is 93 %. Multicentric trials and publication of all such cases are needed to determine algorithms for diagnosis and management of small bowel obstruction caused by instrumental uterine perforation

Process development of a human recombinant diabody expressed in E. coli: engagement of CD99-induced apoptosis for target therapy in Ewing's sarcoma

Ewing's sarcoma (EWS) is the second most common primary bone tumor in pediatric patients characterized by over expression of CD99. Current management consists in extensive chemotherapy in addition to surgical resection and/or radiation. Recent improvements in treatment are still overshadowed by severe side effects such as toxicity and risk of secondary malignancies; therefore, more effective strategies are urgently needed. The goal of this work was to develop a rapid, inexpensive, and "up-scalable" process of a novel human bivalent single-chain fragment variable diabody (C7 dAbd) directed against CD99, as a new therapeutic approach for EWS. We first investigated different Escherichia coli constructs of C7 dAbd in small-scale studies. Starting from 60 % soluble fraction, we obtained a yield of 25 mg C7 dAbd per liter of bacterial culture with the construct containing pelB signal sequence. In contrast, a low recovery of C7 dAbd was achieved starting from periplasmic inclusion bodies. In order to maximize the yield of C7 dAbd, large-scale fermentation was optimized. We obtained from 75 % soluble fraction 35 mg C7 dAbd per L of cell culture grown in a synthetic media containing 3 g/L of vegetable peptone and 1 g/L of yeast extract. Furthermore, we demonstrated the better efficacy of the cell lysis by homogenization versus periplasmic extraction, in reducing endotoxin level of the C7 dAbd. For gram-scale purification, a direct aligned two-step chromatography cascade based on binding selectivity was developed. Finally, we recovered C7 dAbd with low residual process-related impurities, excellent reactivity, and apoptotic ability against EWS cells