Monitoring the protective effects of minocycline treatment with radiolabeled annexin V in an experimental model of focal cerebral ischemia.

Minocycline is an antibiotic now recognized to have antiapoptotic and antiinflammatory properties. Because of these properties, minocycline may be of benefit in reducing neuronal apoptosis from ischemia and subsequent postischemic inflammation if administered soon after a stroke. We now explore the feasibility of using (99m)Tc-annexin V, an in vivo marker of apoptosis, with SPECT to monitor the antiapoptotic effects of minocycline therapy. METHODS: CB6/F1 adult male mice underwent unilateral distal middle cerebral artery occlusion (dMCA) occlusion and were imaged and sacrificed at 1, 3, 7, or 30 d after injury. Animals were given minocycline (or vehicle) 30 min and 12 h after dMCA occlusion and then given 22.5 mg/kg twice daily for up to 7 d. Before imaging, behavioral tests were performed to evaluate the neurologic function. After imaging, brains were collected for histology and assessed for the degree of apoptosis and microglial activation. RESULTS: (99m)Tc-Annexin V uptake in injured hemispheres was significantly decreased 2- to 3-fold by minocycline at all time points. Minocyline reduced infarct size as seen histologically and improved behavioral indices as late as 30 d. Infarct volume as seen histologically correlated with radiolabeled annexin V uptake seen by SPECT. In situ fluorescent microscopy demonstrated that annexin V bound primarily to neurons at 1 and 3 d, with a shift toward microglia by 7 and 30 d. CONCLUSION: We found that minocycline significantly reduces neuronal apoptosis and infarct size and improves neurologic outcome in mice after acute focal cortical ischemia.     

Prophylactic laparoscopic-assisted total gastrectomy for hereditary diffuse gastric cancer.

BACKGROUND: Ten percent of gastric cancer (GC) cases are familial, with one third resulting from a mutation in the tumor suppressor gene CDH1. Loss of this important structure can result in hereditary diffuse gastric cancer (HDGC), which carries a high mortality if early diagnosis is not made. Despite its clear genetic origin, optimal management of HDGC family members is controversial, as the utility and efficacy of current cancer screening programs for mutation carriers are unproven. METHODS: A 53-year-old Caucasian woman was initially seen for genetic screening because multiple family members had mutations of the CDH1 gene. Her pedigree analysis demonstrated 4 generations of gastric cancer, and 2 of the generations carried the CDH1 germline mutation, consistent with HDGC. At endoscopy, the patient's gastric mucosa was normal and random biopsies were also normal. The patient underwent a laparoscopic total gastrectomy. RESULTS: The gross examination of her stomach appeared normal. On histologic examination, however, the stomach was found to have diffuse (signet ring cell) adenocarcinoma in-situ with 11 microscopic foci of invasive adenocarcinoma limited to the lamina propria. CONCLUSION: Our case is the first reported prophylactic total gastrectomy utilizing a laparoscopic approach, and it highlights the importance of taking a thorough family history and obtaining a pedigree analysis. Endoscopic screening in HDGC cannot rule out diffuse GC, because the stomach and biopsies can be normal despite the presence of adenocarcinoma. Therefore, our case supports the recommendation for prophylactic gastrectomy in HDGC.     

Psychosocial factors at work and perceived health among agricultural meat industry workers in France

Objective  The objective of this study was to describe the perceived health status of the meat industry employees—i.e., working in the slaughtering, cutting, and boning of large animals and poultry—and its relation to their organisational and psychosocial constraints at work. Methods  This postal survey included all 3,000 employees of the meat industry (beef, pork and poultry) in four districts in Brittany, France, whose companies were affiliated with the agricultural branch of the national health insurance fund. The questionnaire asked for social and demographic data and information describing their job and the organisation of their work. The psychosocial factors at work were described according to Karasek’s questionnaire (demand, latitude and social support at work). Perceived health was measured with the Nottingham Health Profile perceived health indicator. Results  This study shows the high prevalence of poor health reported by the workers in this industry. This poor perceived health was worse in women and increased regularly with age. Among the psychosocial factors studied, high quantitative and qualitative demand at work, inadequate resources for good work and to a lesser extent, inadequate prospects for promotion appear especially associated with poor perceived health. Other factors often associated with poor perceived health included young age at the first job and work hours that disrupt sleep rhythms (especially for women). Conclusion  Our results show that this population of workers is especially vulnerable from the point of view of perceived physical and psychological health and is exposed to strong physical, organisational and psychosocial constraints at work. They also demonstrate that poor perceived health is associated with some psychosocial (such as high psychological demand and insufficient resources) and organisational factors at work. These results, in conjunction with those from other disciplines involved in studying this industry, may help the companies to develop preventive activities.     

Retentissement osseux de l’anorexie mentale

The objective of this study was to evaluate the epidemiology, diagnosis, pathophysiology, and treatment of bone loss related to anorexia nervosa. Earlier onset and longer duration of anorexia nervosa are associated with more severe bone loss. Osteoporosis develops in 38 to 50% of cases. Bone mineral density measurement by dual-energy X-ray absorptiometry is useful for assessing bone mass, and bone marker assays provide information on bone turnover. Bone loss in anorexia nervosa is probably multifactoriel. Estrogen deficiency was long felt to be the major factor. However, in contrast to postmenopausal osteoporosis, bone loss associated with anorexia nervosa is related mainly to inadequate bone formation, with only a slight increase in bone resorption. This suggests a role for nutritional factors, such as disturbances in the growth hormone-somatomedin C axis (GH/IGF-I) related to malnutrition. The best treatment strategy for correcting bone mass in patients with anorexia nervosa is not agreed on. Resumption of menstrual cycles and weight gain seem necessary but not always sufficient. Studies found no benefits with estrogen therapy, but this was usually given as estrogen–progestin contraceptives. No vast studies evaluating hormone replacement therapy have been reported. Bone formation enhancers such as IGF-I seem to provide the best results, most notably when used in combination with estrogens. This suggests that complex treatment strategies combining bone formation enhancers and bone resorption inhibitors may deserve evaluation.     

Functional Results Following Elective Laparoscopic Sigmoidectomy After CT-Proven Diagnosis of Acute Diverticulitis Evaluation of 43 Patients and Review of the Literature

We performed a prospective study to analyze the functional results following elective laparoscopic sigmoidectomy for computed tomography (CT)-proven diagnosis of acute diverticulitis and review the literature. Forty-three of 45 available patients (96%) who had laparoscopic sigmoidectomy for CT-proven acute diverticulitis answered, after a mean time of 40 months, a questionnaire exploring new abdominal symptoms, bowel function, and the patient’s own judgement of the surgical outcome. Surgical technique aimed at removing all the sigmoid by taking down the splenic flexure and do a colorectal anastomosis. Four patients (9%) complained of new abdominal pain. Bowel function was reported as better for 24 patients (56%), unchanged for 16 patients (37%), and worse for 3 (7%). Twenty patients (47%) considered their final result as excellent to good, 17 patients (40%) as satisfying, and 6 patients (13%) as mediocre. Male gender, absence of preoperative history compatible with an irritable bowel syndrome, length of resected sigmoid and residual acute inflammation on histology are statistically predictive of a better postoperative degree of satisfaction. After elective laparoscopic sigmoidectomy for CT-proven diverticulitis, a great majority of patients are very satisfied with their postoperative general comfort.