The Histocompatibility System in Juvenile, Insulin-Dependent Diabetic Multiplex Kindreds

We have histocompatibility (HLA) genotyped 24 families with two or more juvenile, insulin-dependent, ketosis-prone diabetic siblings. This criterion for family selection was used to obtain a homogeneous form of diabetes within a sibship, because diabetes appears to be a genetically heterogeneous disease. 58 diabetic and 53 nondiabetic sibs and 40 parents were studied. 55% of the diabetic pairs were concordant for both HLA haplotypes (expected 25%), 40% were concordant for one haplotype (expected 50%), and 5% were discordant for both haplotypes (expected 25%). These values are significantly different from the expected values (P < 0.001). On the other hand, the inheritance of haplotypes among the nondiabetic sibs in these families was not significantly different from the expected mendelian segregation.     

Exclusive involvement of folliculosebaceous units by herpes: a reflection of early herpes zoster

The histopathological changes of herpes simplex, herpes zoster, and varicella are considered to be indistinguishable from one another. Evaluation of the clinical setting, with adjunctive studies if necessary, generally clarifies the specific diagnosis. Vesicular lesions in all three conditions can involve epidermal and adnexal epithelium with characteristic cytopathic features. We describe three patients with non-vesicular eruptions on the head and neck whose biopsies revealed exclusive folliculosebaceous involvement by herpes. All three patients developed typical herpes zoster within days of the biopsy. There is compelling scientific evidence in the literature indicating that, in herpes zoster, the virus is transported from dorsal root or trigeminal ganglia via myelinated nerves to the skin. These terminate at the isthmus of hair follicles and primary infection of follicular and sebaceous epithelium occurs. Spread of infection to the epidermis follows. In contrast, data pertaining to recurrent herpes simplex indicates that axonal transport of the virus from sensory ganglia to the skin is directed primarily to the epidermis, via terminal non-myelinated nerve twigs. The clinical evolution of our three cases and scientific data in the literature indicate that exclusive folliculosebaceous involvement by herpes, in the setting of a non-vesicular eruption, represents early herpes zoster.     

Nonepileptic seizures: reframing the diagnosis

PROBLEM: Protocols for disclosing the diagnosis of psychological pseudoseizures have been developed. However, outcomes have not been carefully studied. METHOD: Using a retrospective design, the investigators evaluated the outcomes by interviewing patients 2 years after diagnosis who received the diagnosis using a specific protocol. FINDINGS: There was a reduction in symptoms demonstrated by reports of lessened intensity of events or actual reduction in the number of events in 86% of those interviewed. CONCLUSION: This protocol proved helpful in the acceptance of the diagnosis and improved adherence to the treatment recommendations after disclosure of the diagnosis.     

Evaluation of glucocorticoid sensitivity in 697 pre-B acute lymphoblastic leukemia cells after overexpression or silencing of MAP kinase phosphatase-1

Purpose To determine the effect of modulating MAP kinase phosphatase-1 (MKP-1) expression levels on cell death induced by glucocorticoid (GC) or hydroxyurea (HU) treatment in the human pre-B acute lymphoblastic leukemia cell line 697.Methods Stable MKP-1 overexpressing transformants of the 697 pre-B acute lymphoblastic leukemia cell line were created and tested for sensitivity to the GC triamcinolone acetonide (TA) and HU, and compared to a control 697 cell line containing normal MKP-1 expression levels. Small interfering RNAs (siRNAs) were designed to inhibit MKP-1 expression and evaluated for their effect on GC-mediated cell death.Results MKP-1 overexpression caused a phenotype of partial resistance to HU-induced apoptosis but not to GC-induced apoptosis. Electroporation of siRNAs effectively silenced MKP-1 expression, and increased sensitivity to TA by 9.6±1.9%.Conclusions Because MKP-1 protects certain tumor cells from chemotherapy-induced apoptosis, its inhibition is being considered as a possible strategy for combination cancer therapy. However, this study suggests that while MKP-1 inhibition may improve the efficacy of DNA damaging agents, it may have only limited utility in combination with glucocorticoids.Grant support: DOE/BER ER63055 to E.W.     

Dramatic reduction in triplet and higher order births in England and Wales

The proportion of multiple births has increased markedly since 1980 in England and Wales. A major contribution to this trend is thought to be the widespread introduction of assisted reproductive technologies. Despite a continuing (but slower) upward trend in twin maternities, analysis of recent data shows that the rate of triplet and higher order births in England and Wales has declined by one-quarter since 1998. This probably reflects both voluntary and statutory regulation of treatment regimes. This downward trend will help alleviate the high burden of perinatal morbidity and mortality associated with multiple births.     

Pediatrician attitudes and practices regarding collaborative asthma education

Pediatric practices were surveyed in 10 regions of the country to determine physician attitudes and practices regarding approaches to asthma education. Many physician respondents thought that nurses were just as effective as physicians in providing asthma education. In almost all practices a physician was involved; in two thirds of practices, an allied health professional; and in almost half of practices (48%), a registered nurse was involved. The type of healthcare professional involved in education was not associated with percentage of patients with Medicaid insurance, practice ownership, or setting. Given the multidisciplinary approach to education in many pediatric practices, quality improvement efforts to enhance asthma education by pediatric practices could be further enhanced by directly involving allied health professionals who practice in primary care settings.     

Dehydroepiandrosterone sulfate (DHEAS) and health: does the relationship differ by sex?

This study uses data from a large, nationally representative sample of older Taiwanese (aged 54 and older in 2000) to investigate sex differences in the relationship between DHEAS and various health outcomes. Data collection included an individual interview, a physical examination, and samples of blood and (12-h) urine. Regression models of health outcomes on DHEAS are estimated in two steps: first, including only controls for age and sex as well as an interaction between DHEAS and sex; and second, adding covariates likely to be related to both DHEAS and health outcomes (e.g. smoking). Results reveal that higher levels of DHEAS are associated with fewer mobility limitations (especially for women), better cognitive function (among women but not men), and better self-rated health (significant only for men but of similar magnitude for women). These findings are in contrast to previous studies conducted in the US and Europe that generally find stronger associations for men than women. Also unlike previous studies, which often demonstrate a negative relationship between DHEAS and depressive symptoms at least for women, we find little evidence of such a relationship for either sex.