IgG human monoclonal anti-DNA autoantibodies from patients with systemic lupus erythematosus

We describe the production of six mouse-human heterohybridomas secreting human IgG anti-dsDNA antibodies derived from patients with systemic lupus erythematosus (SLE). Peripheral blood cells used for fusion experiments were from patients who were shown to have high numbers of anti-DNA secreting B cells in the peripheral blood. All monoclonal antibodies bind to dsDNA in ELISA systems, five are reactive with Crithidia lucilae kinetoplasts and three precipitate dsDNA in the Farr assay. Inhibition studies revealed a remarkable specificity for certain polynucleotide structures. To our knowledge these are the first hybridomas described in the human system that secrete anti-dsDNA antibodies of the IgG class.     

Expression of bcl-6 and CD10 protein is associated with longer overall survival and time to treatment failure in follicular lymphoma

Follicular lymphomas (FLs) are a heterogeneous group of tumors, but prognostic factors are evaluated insufficiently in this common hematologic neoplasm. While bcl-6 and CD10 are expressed characteristically in FLs, their significance for biologic behavior of FL has not been studied previously. Samples from 73 patients with FL and clinical follow-up from 7 to 231 months were evaluated by immunohistochemical analysis. Patients with high levels of bcl-6 expression had favorable overall survival (OS) (P = .003), disease-specific survival (DSS) (P = .033), and time to treatment failure (P = .003) compared with patients with low levels of bcl-6 expression. Multivariate analysis showed that the results for OS, DSS, and time to treatment failure were independent of the international prognostic index. Patients with CD10+ FLs also had longer OS (P = .001), DSS (P = .007), and time to treatment failure (P = .004), and grade 1 FL was associated with better OS (P = .01) and a statistical trend for longer DSS (P = .05) and time to treatment failure (P = .05), but these results were not independent of bcl-6 expression or the international prognostic index in multivariate analysis.     

Belastungsabhängige Dysphonie, rezidivierende Pleuropneumonie und supraglottische Raumforderung

Urbach-Wiethe syndrome (hyalinosis cutis et mucosae) is an autosomal-recessive inherited disease. It often presents with typical symptoms such as skin lesions (especially in the face and neck area), dyspnea, and maldigestion. Hoarseness is a leading symptom in young children. These manifestations are caused by the assimilation of glycoproteins in mesenchymal tissue. Our case report shows that hoarseness does not necessarily appear only in children, but can also appear later. Furthermore, the assimilation of glycoproteins in the supraglottic area may also cause dysphonia. Due to the varied features of this disease, interdisciplinary check-ups are necessary at regular intervals.     

Declining child mortality in northern Malawi despite high rates of infection with HIV

Objective

To determine whether routine surveys, such as the Demographic and Health Surveys (DHS), have underestimated child mortality in Malawi.

Methods

Rates and causes of child mortality were obtained from a continuous-registration demographic surveillance system (DSS) in Malawi for a population of 32 000. After initial census, births and deaths were reported by village informants and updated monthly by project enumerators. Cause of death was established by verbal autopsy whenever possible. The likely impact of human immunodeficiency virus (HIV) infection on child mortality was also estimated from antenatal clinic surveillance data. Overall and age-specific mortality rates were compared with those from the 2004 Malawi DHS.

Findings

Between August 2002 and February 2006, 38 617 person–years of observation were recorded for 20 388 children aged < 15 years. There were 342 deaths. Re-census data, follow-up visits at 12 months of age and the ratio of stillbirths to neonatal deaths suggested that death registration by the DSS was nearly complete. Infant mortality was 52.7 per 1000 live births, under-5 mortality was 84.8 per 1000 and under-15 mortality was 99.1 per 1000. One-fifth of deaths by age 15 were attributable to HIV infection. Child mortality rates estimated with the DSS were approximately 30% lower than those from national estimates as determined by routine surveys.

Conclusion

The fact that child mortality rates based on the DSS were relatively low in the study population is encouraging and suggests that the low mortality rates estimated nationally are an accurate reflection of decreasing rates.     

Feminist perspectives on the social construction of chronic fatigue syndrome

We contrast Western medical views of chronic fatigue syndrome (CFS) etiology, diagnosis, and treatment with views maintained by a predominantly female CFS population. We argue that the failure of Western medicine to demonstrate a viral etiology for CFS led to a paradigmatic shift in research perspectives, which then embraced psychiatric and sociocultural explanations for CFS. As a result, CFS was delegitimized as a biomedical phenomenon within medical, academic, governmental, and public arenas. We compare alternative social constructions of CFS with issues pertaining to multiple sclerosis (MS), an illness that similarly predominates among women. Patient perspectives suggest that the history of medical attitudes toward CFS may eventually parallel the transformations that occurred in relation to MS. In particular, the discovery of biological markers for CFS may lay to rest the categorization of CFS as largely within the psychiatric realm.     

Sample size in cluster‐randomized trials with time to event as the primary endpoint

In cluster‐randomized trials, groups of individuals (clusters) are randomized to the treatments or interventions to be compared. In many of those trials, the primary objective is to compare the time for an event to occur between randomized groups, and the shared frailty model well fits clustered time‐to‐event data. Members of the same cluster tend to be more similar than members of different clusters, causing correlations. As correlations affect the power of a trial to detect intervention effects, the clustered design has to be considered in planning the sample size. In this publication, we derive a sample size formula for clustered time‐to‐event data with constant marginal baseline hazards and correlation within clusters induced by a shared frailty term. The sample size formula is easy to apply and can be interpreted as an extension of the widely used Schoenfeld's formula, accounting for the clustered design of the trial. Simulations confirm the validity of the formula and its use also for non‐constant marginal baseline hazards. Findings are illustrated on a cluster‐randomized trial investigating methods of disseminating quality improvement to addiction treatment centers in the USA. Copyright © 2012 John Wiley & Sons, Ltd.     

Trends in maternal mortality ratio among women of German and non-German nationality in West Germany, 1980-1996

BACKGROUND: Maternal mortality is a sensitive indicator for inequity in health. We describe recent trends in overall and cause-specific maternal mortality ratio among women of German and non-German nationality residing in West Germany. METHODS: Using birth and death register data for 1980-1996 we related 1067 cases of maternal death (ICD 9: 630-676) to 11.2 million live births. We assessed the effects of nationality and of marital status, a proxy for socioeconomic status, controlling for year of death and age of the mother in a Poisson regression model. RESULTS: Maternal mortality ratio in West Germany decreased from 13 per 100000 live births in 1980-1988 to 6.1 in 1989-1996. The crude relative risk for non-German nationality decreased from 1.9 (95% CI: 1.6-2.3) to 1.3 (1.0-1.7); after adjusting for age, year of death and marital status it was 1.7 (95% CI: 1.4-2.1) and 1.6 (95% CI: 1.2-2.1). Unmarried women incurred an adjusted relative risk of 1.8 (95% CI: 1.5-2.3). Non-German women experienced an excess mortality from abortions which largely disappeared in 1989-1996; concurrently, being unmarried no longer conveyed an additional risk to them. The risk status of German mothers developed unfavourably: increasing proportions are unmarried, which continues to be a marker of elevated relative risk in this group. CONCLUSIONS: Our findings suggest continuously improving accessibility and quality of obstetric services, in particular for women of non-German nationality. Still, inequity in maternal risk continues to exist. Maternal risk, however, is not determined by the simple distinction 'German' versus 'non-German'; its association with socioeconomic status extends beyond nationality.     

Occupational lung cancer risk for men in Germany: results from a pooled case-control study

Occupational exposures such as crystalline silica, diesel engine exhaust, polycyclic aromatic hydrocarbons, and man-made mineral fibers are strongly suspected to increase lung cancer risk. Two case-control studies in Germany conducted between 1988 and 1996 were pooled for a joint analysis. A total of 3,498 male cases and 3,541 male population controls, frequency matched for age and region, were included in the study. The lifelong history of all jobs and industries was coded and occupational exposures were evaluated by expert rating. Odds ratios, crude and adjusted for smoking and asbestos exposure, were calculated by conditional logistic regression. Job-related evaluation showed a statistically significant increased odds ratio adjusted for smoking among farmers; forestry workers, fishermen, and livestock workers; miners and quarrymen; chemical processors; cabinet makers and related wood workers; metal producers and processors; bricklayers and carpenters; road construction workers, pipelayers and well diggers; plasterers, insulators, and upholsterers; painters and lacquerers; stationary engine and heavy equipment operators; transport workers and freight handlers; and service workers. With regard to specific occupational exposures, elevated odds ratios (OR) (95% confidence intervals (CI)) for lung cancer risk adjusted for smoking and asbestos exposure were observed for man-made mineral fibers (OR = 1.48, 95% CI 1.17, 1.88); crystalline silica (OR = 1.41, 95% CI 1.22, 1.62); diesel engine exhaust (OR = 1.43, 95% CI 1.23, 1.67); and polycyclic aromatic hydrocarbons (OR = 1.53, 95% CI 1.14, 2.04). The risk of asbestos exposure, adjusted for smoking was also increased (OR = 1.41, 95% CI 1.24, 1.60).     

Effects of 2,4-dichlorophenoxyacetic acid on the ventral prostate of rats during the peri-pubertal,pubertal and adult stage

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is used on a wide variety of terrestrial and aquatic broadleaf weeds. 2,4-D has been shown to produce a wide range of adverse effects on animal and human health. The aim of the current study was to evaluate the effects of pre- and postnatal exposure to 2,4-D on rat ventral prostate (VP). Pregnant rats were exposed daily to oral doses of 70?mg/kg/day of 2,4-D from 16 days of gestation up to 23 days after delivery. Then, the treated groups (n?=?8) were fed with a 2,4-D added diet until sacrificed by decapitation on postnatal day (PND) 45, 60, or 90. Morphometric studies were performed and androgen receptor (AR) protein levels in the VP were determined. AR, insulin-like growth factor-I (IGF-1) and insulin-like growth factor-I receptor (IGF-1R) mRNA expression in the VP along with testosterone (T), dihydroxytestosterone (DHT), growth hormone (GH) and IGF-1 serum levels were also determined to ascertain whether these parameters were differentially affected. Results of this study showed that 2,4-D exposure during gestation and until adulthood altered development of the prostate gland in male rats, delaying it at early ages while increasing its size in adults, indicate that 2,4-D could behave as endocrine disruptors (EDs).     

A bioassay for mosquito repellency against Aedes aegypti: method validation and bioactivities of DEET analogues

Objectives Vector‐borne diseases are still a major mortality factor in Africa and South‐east Asia and effective mosquito repellents are therefore needed. An efficient and safe in‐vitro assay system using artificial blood and skin substitute could facilitate the development of novel repellents, as most assays currently rely on human subjects or vertebrate whole blood. Moreover, examining the skin permeation profiles could provide safer mosquito repellents. The new assay system could serve as an initial system for testing new repellent candidates upon validation with DEET and its analogues. Methods N,N‐Diethyl‐meta‐toluamide (DEET) and five analogues were synthesised and used to validate a novel in‐vitro bioassay using artificial blood and collagen membrane. Repellency against Aedes aegypti was correlated with lipophilicity and skin permeation. Key findings The new in‐vitro assay showed good reproducibility (interday relative standard deviation <10% at high concentrations). Four of the five DEET analogues showed repellency similar or superior to that of DEET. Repellency correlated linearly with lipophilicity but stronger repellents tended to permeate skin better. Conclusions The new in‐vitro assay using blood substitute and collagen membrane significantly simplifies screening of possible mosquito repellents. Lipophilicity as well as skin permeation profiles should be considered before testing of compounds that are candidates for mosquito repellents.