Anaphylaxis after treatment with recombinant factor VIII

BACKGROUND: Treatment of hemophilia patients with recombinant factor VIII concentrates has not previously been associated with anaphylaxis. STUDY DESIGN AND METHODS: A 5-week-old boy with severe hemophilia A developed dyspnea, cyanosis, hypotension, and a diffuse urticarial rash following treatment with a recombinant factor VIII (Recombinate). To identify the cause of anaphylaxis in this patient, the vial lot was examined for the presence of endotoxin, and a checkerboard immunoblotting technique was used to test serum and/or plasma samples from the patient and mother for the presence of antibodies (IgA, IgG, IgE, and IgM) to Recombinate-related antigens (recombinant factor VIII, von Willebrand factor, human serum albumin, Chinese hamster ovary proteins, bovine serum albumin, mouse monoclonal anti-human factor VIII, polyethylene glycol 3350), and to ethylene oxide, the agent used to sterilize the infusion equipment. RESULTS: No immune response directed against the Recombinate-related antigens or ethylene oxide that could be associated with the anaphylactic reaction was identified. Endotoxin was not present upon rabbit pyrogen testing of the therapeutic product. CONCLUSION: These studies failed to show any association between Recombinate and the onset of the allergic reaction. This seems to be the first reported case of anaphylaxis following the infusion of a recombinant form of factor VIII concentrate.     

2型糖尿病患者勃起功能障碍患病率及西地那非的疗效和安全性评价

目的调查内分泌门诊中糖尿病患者阴茎勃起功能障碍(ED)患病率,并评价西地那非(万艾可)在糖尿病合并ED患者中的疗效和安全性。方法多中心收集2型糖尿病男性患者6193例,入选6178例,患者签署知情同意书后,根据国际勃起功能指数表(IIEF5)患者进行自我评分。对3个月内服用3剂万艾可的患者除要求填写治疗前的IIEF5表评分外,还要求填写治疗后的总体疗效问题回答表,以评价万艾可治疗的疗效,并记录患者服药后的不良事件以评价其安全性。结果国内42家医院内分泌门诊2型糖尿病患者中ED的患病率为75.2%,其中重度、中度和轻度ED分别为9.1%、17.2%、48.9%。该受检人群中ED的知晓率为85.0%,但治疗率仅为9.4%。多因素回归分析显示患者年龄、糖尿病病程、血糖控制不佳(HbA1C>6.5%)与糖尿病患者ED的发生独立相关。共有389例患者服用万艾可治疗,治疗后患者IIEF5总评分和各问题的评分均显著高于治疗前(P<0.01);根据IIEF5评分,治疗后重、中度ED患者例数明显少于治疗前(P<0.01)。根据总体疗效评估问题的回答,给予万艾可治疗后勃起功能改善率达86.4%。对安全性评价显示服用万艾可后出现的与药物有关的不良事件主要是颜面潮红、头痛、心悸和口干等,大多为轻度。结论在2型糖尿病患者中ED是常见的合并症,万艾可治疗糖尿病合并ED疗效确切,并有良好的安全性。     

The phospholipase A2 inhibitor methyl indoxam suppresses diet-induced obesity and glucose intolerance in mice

Background and purpose:

Previous results have shown that mice lacking in the group 1B phospholipase A₂ (Pla2g1b) are resistant to obesity and diabetes induced by feeding a diabetogenic high-fat/high-carbohydrate diet. This study examined the potential of using the Pla2g1b inhibitor methyl indoxam as therapy to suppress diet-induced obesity and diabetes.

Experimental approach:

Male C57BL/6 mice were fed the diabetogenic diet with or without methyl indoxam supplementation. Body weight gain, fasting plasma glucose levels, glucose tolerance and postprandial lysophospholipid absorption were compared.

Key results:

Wild-type C57BL/6 mice fed the diabetogenic diet without Pla2g1b inhibitor showed 31 and 69% body weight gain after 4 and 10 weeks respectively. These animals also showed elevated plasma glucose levels and were glucose intolerant. In contrast, C57BL/6 mice fed the diabetogenic diet with 90 mg·kg⁻¹ of methyl indoxam gained only 5% body weight after 10 weeks. These animals were also euglycaemic and displayed normal glucose excursion rates in glucose tolerance test. Methyl indoxam suppression of diet-induced body weight gain and glucose intolerance was correlated with the inhibition of Pla2g1b-mediated postprandial lysophospholipid absorption.

Conclusions and implications:

These results show that oral supplementation of a diabetogenic diet with the Pla2g1b inhibitor methyl indoxam effectively suppresses diet-induced obesity and diabetes in mice. This suggests that Pla2g1b inhibition may be a potentially effective oral therapeutic option for treatment of obesity and diabetes.     

Students' expectations of postregistration degree programmes

The needs of postregistration students pursuing degree-linked clinical courses have received little attention and there are few insights concerning their aspirations when they enrol on such courses. Thus the aim of this study was to explore postregistration students' perceptions of the specific needs of their patient/client group and to examine how they envisaged the course on which they had just enrolled might help them to meet these needs in addition to their own requirements for professional and personal development. Data were collected by group interview from 62 students enrolling on eight different postregistration courses, all employed in an acute hospital trust. The results were analysed inductively. They indicated that students had internalized the state of the healthcare market and were keenly aware of the need to fulfil the expectations of employers and the public, while fulfilling their own needs for education and pursuing their own professional and career trajectories. They appeared ambitious and yet appeared to demonstrate empathy for patients and their families and felt a tremendous desire to provide care of a high quality through the optimal development of technical expertise. Students' emphasis on the importance of keeping abreast of technological developments should not be lightly dismissed considering its prominent position within the acute areas where they were employed, especially as it did not replace their desire to promote the caring aspects of their work.     

Bullying and people with severe intellectual disability

Although bullying has been shown to reduce quality of life in many spheres, anti‐bullying strategies have yet to be incorporated into services for adults with severe intellectual disability (ID). The present study employed a survey of staff and parent concerns about 54 previously surveyed students who had left a school for pupils with severe ID. A content analysis of follow‐up interviews was performed in 10 cases. Staff identified 19% of the survey sample as bullying others and 11% as being picked on. Neither gender nor communication ability had an impact. There was no significant change in bully or victim status over time, although some people did change. Parents or staff raised bully/victim problems in more than half of the interviews. There is sufficient evidence of bullying behaviour to warrant the adoption of anti‐bullying strategies.     

Response from lieberman and colleagues

Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165