Detection of haptenated proteins in organotypic human skin explant cultures exposed to dapsone.

Bioactivation of parent drug to reactive metabolite(s) followed by protein haptenation has been suggested to be a critical step in the elicitation of cutaneous drug reactions. Although liver is believed to be the primary organ of drug bioactivation quantitatively, other organs including skin may also metabolize drugs. Cultured human epidermal keratinocytes and dermal fibroblasts have been shown to be capable of bioactivating sulfonamides and sulfones, giving rise to haptenated proteins. It is, however, unclear whether metabolic events in these isolated cells reflect bioactivation in vivo. Hence, split-thickness human skin explants were exposed to dapsone (DDS) or its arylhydroxylamine metabolite (dapsone hydroxylamine, D-NOH) and probed for protein haptenation. DDS and D-NOH were applied either epicutaneously or mixed in the medium (to mimic its entry into skin from the systemic circulation). DDS-protein adducts were readily detected in skin explants exposed to either DDS or D-NOH. Adducts were detected mainly in the upper epidermal region in response to epicutaneous application, whereas adducts were formed all over the explants when DDS/D-NOH were mixed in the culture medium. In addition, adducts were visible in HLA-DR+ cells, indicating their presence in the dendritic cell population in the skin. Our results demonstrate the ability of intact human skin to bioactivate DDS leading to protein haptenation.     

Pseudoexfoliation as a risk factor for prevalent open‐angle glaucoma

Purpose: To estimate the risk of open‐angle glaucoma (OAG) associated with exposure to pseudoexfoliation (PEX) and increased intraocular pressure (IOP). Methods: In 1984?86, a cross‐sectional, population‐based survey was conducted in the municipality of Tierp, central Sweden. Its target population comprised 2429 residents aged 65–74 years. In addition to a sample of 760 people, patients previously diagnosed with glaucoma were examined. The prevalence of OAG in the target population was estimated from the prevalence in the sample and patients already diagnosed. A review of prevalent cases in 1984–86 was undertaken in 2006. Results: Definite OAG was established in 77 cases, corresponding to a prevalence of 5.3% (95% confidence interval [CI] 4.4–6.2). Of these, 23 represented newly detected cases. The prevalence of PEX was 17.2% (95% CI 14.6–19.9), calculated from 134 cases in the population sample. When adjusting for gender, PEX was associated with a 4.7‐fold (95% CI 2.2–9.4) increased risk of OAG. For clinical cases only, the risk was 16‐fold (95% CI 4.8–56) greater in subjects with PEX, compared with those without PEX. In individuals without a previous diagnosis of glaucoma, an IOP ≥ 20 mmHg was associated with a 9.7‐fold (95% CI 3.7–27) increased risk, but PEX alone was not a risk factor for OAG (adjusted odds ratio = 0.96). Conclusions: Pseudoexfoliation was associated with OAG only in people previously diagnosed with the disease. In cases detected in the population‐based survey, increased IOP was a serious risk factor.     

Important prognostic factors for the long-term survival of lung cancer subjects in Taiwan

Background  

This study used a large-scale cancer database in determination of prognostic factors for the survival of lung cancer subjects in Taiwan.     

Brustkrebs-Früherkennung in Deutschland

The guideline Early Detection of Breast Cancer in Germany aims to assist physicians, healthy women, and patients in decision making with recommendations based on evidence and formal consensus regarding the diagnostic chain of health care for early detection of breast cancer. This guideline updates the previous version of 2003. The guideline is a precondition to establishing an effective and efficient national early breast cancer detection program in accordance with the requirements of the European Council and the World Health Organization for cancer control programs. The core imaging technique of an early detection program is mammography, whether used for screening or diagnosis. Breast health care outcomes can be improved by embedding this imaging technology in a quality-assured diagnostic chain. The guideline comprises areas of present scientific and medical knowledge, based on evidence and consensus and covering all multidisciplinary aspects of the diagnostic chain, including clinical history taking, risk consultation and communication, breast health awareness, physical breast examination, breast imaging, interventional guided biopsy, excision biopsy, and breast pathology. The guideline provides formal measures as quality indicators to ensure resource availability, process quality, and outcome of the diagnostic chain. Early detection of breast cancer is presently the most promising chance for optimizing diagnosis and treatment of breast cancer in order to reduce mortality and morbidity while improving survivors’ quality of life. The aim is to detect breast cancer as a noninvasive disease or an invasive disease at an early stage, with a 5-year survival rate of more than 90% with adequate treatment. Detecting more noninvasive breast cancer might even help reduce the incidence. Within the scope of secondary prevention, early detection offers the chance of cure at an early disease stage by less intensive treatment.     

Triggering of sudden death from cardiac causes by vigorous exertion

BACKGROUND: Retrospective and cross-sectional data suggest that vigorous exertion can trigger cardiac arrest or sudden death and that habitual exercise may diminish this risk. However, the role of physical activity in precipitating or preventing sudden death has not been assessed prospectively in a large number of subjects. METHODS: We used a prospective, nested case-crossover design within the Physicians' Health Study to compare the risk of sudden death during and up to 30 minutes after an episode of vigorous exertion with that during periods of lighter exertion or none. We then evaluated whether habitual vigorous exercise modified the risk of sudden death that was associated with vigorous exertion. In addition, the relation of vigorous exercise to the overall risk of sudden death and nonsudden death from coronary heart disease was assessed. RESULTS: During 12 years of follow-up, 122 sudden deaths were confirmed among the 21,481 male physicians who were initially free of self-reported cardiovascular disease and who provided information on their habitual level of exercise at base line. The relative risk of-sudden death during and up to 30 minutes after vigorous exertion was 16.9 (95 percent confidence interval, 10.5 to 27.0; P<0.001). However, the absolute risk of sudden death during any particular episode of vigorous exertion was extremely low (1 sudden death per 1.51 million episodes of exertion). Habitual vigorous exercise attenuated the relative risk of sudden death that was associated with an episode of vigorous exertion (P value for trend=0.006). The base-line level of exercise was not associated with the overall risk of subsequent sudden death. CONCLUSIONS: These prospective data from a study of U.S. male physicians suggest that habitual vigorous exercise diminishes the risk of sudden death during vigorous exertion.     

Abbreviated endometriosis-associated infertility correlates with in vitro fertilization success

The utility of in vitro fertilization (IVF) for refractory infertility associated with endometriosis was studied by reviewing the 6-year experience with IVF and pregnancy follow-up at University Hospital, London, Ontario. Two hundred forty cycles were begun in 124 couples in whom endometriosis was the sole identified cause of infertility. In a program employing predominantly ultrasoundguided transvaginal oocyte retrieval, live birth rates were not reduced with advanced degrees of endometriosis. Live births were positively correlated with a shorter infertility duration.Presented, in part, at the 46th Annual Meeting of the Society of Obstetricians and Gynaecologists of Canada, Halifax, Nova Scotia, June 20, 1990.     

Endogenous luteinizing hormone surges following administration of human chorionic gonadotropin: Further evidence for lack of loop feedback in humans

The existence of inhibitory short- and ultrashort-loop feedback mechanisms for luteinizing hormone (LH), while documented in animals, has been questioned in humans. Since human chorionic gonadotropin (hCG) binds to LH receptors but can be distinguished from LH in immunoassays, it is possible to identify LH surges in the face of exogenously administered hCG. The present study demonstrates LH surges at midcycle in normal volunteers and in women undergoing controlled ovarian hyperstimulation, given hCG. This provides further evidence for lack of loop feedback control of LH secretion in humans.     

Motives for parenthood and response to failed in vitro fertilization: Implications for counseling

The purpose of this investigation was to identify in vitro fertilization (IVF) candidates' motives for parenthood and hence for seeking treatment. The relationship among identified motives, pretreatment emotional adjustment, and reaction to treatment failure was then examined. Women as a group placed greatest emphasis on fulfilling gender-role requirements, and those strongly endorsing such motives showed the poorest adjustment before IVF and the most negative reaction to first-cycle failure. In contrast, men in general were more likely to stress a desire for marital completion, although this motive was not predictive of emotional status before or after IVF. However, men experiencing social pressures to have children were at greater risk when treatment failed. The results indicate that greater consideration of cognitive factors may enhance understanding of emotional reactions to IVF failure and provide important insights for therapeutic intervention.