Serum vitamin D metabolite levels and the subsequent development of prostate cancer (Hawaii, United States)

Objectives: Because several serum studies of vitamin D metabolites have produced equivocal results on their relation to prostate cancer risk, the purpose of this study is to evaluate this association further.Methods: A nested case-control study in a cohort of 3,737 Japanese-American men examined from 1967 to 1970 was conducted in Hawaii (United States). At the time of examination, a single blood specimen was obtained, and the serum was frozen. After a surveillance period of over 23 years, 136 tissue-confirmed incident cases of prostate cancer were identified. Their stored sera and those of 136 matched controls were measured for the following: 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, calcium, phosphorus, and parathyroid hormone.Results: There were no notable differences between cases and controls in their median serum levels of the five laboratory measurements. Odds ratios (OR) for prostate cancer, based on the quartiles of serum levels in controls, were also determined. The ORs for the highest quartiles relative to the lowest were 0.8 (95 percent confidence interval [CI] = 0.4-1.8) for 25-hydroxyvitamin D and 1.0 (CI = 0.5-2.1) for 1,25-dihydroxyvitamin D.Conclusion: It is possible that the lack of sufficient numbers of study subjects with low vitamin D levels affected the results. Nonetheless, the findings suggest that there is a lack of a strong association between vitamin D and prostate cancer.     

Altered mRNA expression for brain-derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase in the hippocampus of patients with intractable temporal lobe epilepsy

The expression of brain-derived neurotrophic factor and the alpha subunit of calcium/calmodulin-dependent protein kinase II mRNA in hippocampi obtained during surgical resections for intractable temporal lobe epilepsy were examined. Both calcium/calmodulin-dependent protein kinase II and brain-derived neurotrophic factor are localized heavily within the hippocampus and have been implicated in regulating hippocampal activity (Kang and Schuman [1995] Science 267:1658-1662; Suzuki [1994] Intl J Biochem 26:735-744). Also, the autocrine and paracrine actions of brain-derived neurotrophic factor within the central nervous system make it a likely candidate for mediating morphologic changes typically seen in the epileptic hippocampus. Quantitative assessments of mRNA levels in epileptic hippocampi relative to autopsy controls were made by using normalized densitometric analysis of in situ hybridization. In addition, correlations between clinical data and mRNA levels were studied. Relative to autopsy control tissue, decreased hybridization to mRNA of the alpha subunit of calcium/calmodulin-dependent protein kinase II and increased hybridization to brain-derived neurotrophic factor mRNA were found throughout the granule cells of the epileptic hippocampus. There also was a significant negative correlation between the duration of epilepsy and the expression of mRNA for brain-derived neurotrophic factor. These results are similar qualitatively to those found in animal models of epilepsy and suggest that chronic seizure activity in humans leads to persistent alterations in gene expression. Furthermore, these alterations in gene expression may play a role in the etiology of the epileptic condition.     

Utilization of "used" vials: cost-effective technique for MR arthrography

Because full vials of commercially available MR arthrographic contrast are expensive, we hypothesized that the small residual contrast in a "used" vial would be adequate for MR arthrography. After sterility testing and quantity analysis of the residual contrast in 28 vials, this method was successfully used in 10 patients. J. Magn. Reson. Imaging 2000;12:953-955.     

Understanding Employee Awareness of Health Care Quality Information: How Can Employers Benefit?

Objective. To analyze the factors associated with employee awareness of employer-disseminated quality information on providers.
Data Sources. Primary data were collected in 2002 on a stratified, random sample of 1,365 employees in 16 firms that are members of the Buyers Health Care Action Group (BHCAG) located in the Minneapolis–St. Paul region. An employer survey was also conducted to assess how employers communicated the quality information to employees.
Study Design. In 2001, BHCAG sponsored two programs for reporting provider quality. We specify employee awareness of the quality information to depend on factors that influence the benefits and costs of search. Factors influencing the benefits include age, sex, provider satisfaction, health status, job tenure, and Twin Cities tenure. Factors influencing search costs include employee income, education, and employer communication strategies. We estimate the model using bivariate probit analysis.
Data Collection. Employee data were collected by phone survey.
Principal Findings. Overall, the level of quality information awareness is low. However, employer communication strategies such as distributing booklets to all employees or making them available on request have a large effect on the probability of quality information awareness. Employee education and utilization of providers' services are also positively related to awareness.
Conclusions. This study is one of the first to investigate employee awareness of provider quality information. Given the direct implications for medical outcomes, one might anticipate higher rates of awareness regarding provider quality, relative to plan quality. However, we do not find empirical evidence to support this assertion.     

Spectacle use and reduced unaided vision in third grade students: a comparative study in different educational settings

Background: The development of myopia is influenced by hereditary factors, environmental factors and geneenvironment interaction. Reading and near‐work activity are associated with myopia and myopic progression. This study sought to determine and compare the prevalence of reduced unaided vision and spectacle use among third grade Israeli students from three different educational settings. Method: A sample of 917 students (mean age 8.5 years, range seven to 10 years) was drawn from the three Israeli educational streams: secular, Orthodox and ultra‐Orthodox. Children in the ultra‐Orthodox education pathway begin studying at the age of three years and their daily reading involves sustained near work with increased accommodative effort accompanied by head‐rocking movements. Reduced distance vision was used to indicate the likely development of or an increase in the amount of myopia. Spectacle lenses were measured to determine the prevalence of myopia. Results: Of the 917 students studied, 103 (11.2 per cent) wore spectacles (14.2 per cent of the males and eight per cent of the females); 82.5 per cent of those who wore spectacles were myopic. Males from ultra‐Orthodox schools had the highest rate of reduced unaided vision (72.5 per cent) compared with males from secular schools (27.3 per cent), males from Orthodox schools (59.3 per cent) or with females from all three groups (average of 34.8 per cent, p < 0.0001, chi squared). Males had a higher rate of reduced unaided vision, especially in the Orthodox and ultra‐Orthodox schools. Conclusions: Our study suggests that Jewish ultra‐Orthodox males have a higher prevalence and degree of myopia. The study habits of young children, including exposure to prolonged near tasks, high accommodative demands and possibly optical defocus induced by body sway, may contribute to the development of myopia.     

Solar disinfection of water for diarrhoeal prevention in southern India.

AIMS: To evaluate the efficacy and acceptability of solar irradiation in the prevention of diarrhoeal morbidity in children under 5 years of age, in an urban slum in Vellore, Tamil Nadu. METHODS: A total of 100 children were assigned to receive drinking water that had been subjected to solar disinfection in polyethylene terephthalate bottles. One hundred age and sex matched controls were also selected. Both groups were followed by weekly home visits for a period of six months for any diarrhoeal morbidity. At the end of the follow up period, the acceptability of the intervention was assessed by interviews, questionnaires, and focus group discussions. RESULTS: There was significant reduction in the incidence, duration, and severity of diarrhoea in children receiving solar disinfected water, despite 86% of the children drinking water other than that treated by the intervention. The incidence of diarrhoea in the intervention group was 1.7 per child-year, and among controls 2.7 per child-year, with an incidence rate ratio of 0.64 (95% CI -0.48 to 0.86). The risk of diarrhoea was reduced by 40% by using solar disinfection. In qualitative evaluation of acceptability, most women felt that solar disinfection was a feasible and sustainable method of disinfecting water. CONCLUSIONS: Solar disinfection of water is an inexpensive, effective, and acceptable method of increasing water safety in a resource limited environment, and can significantly decrease diarrhoeal morbidity in children.     

Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes.

PURPOSE: This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome. EXPERIMENTAL DESIGN: In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks. RESULTS: In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths. CONCLUSIONS: On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda.gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.     

Application of a statistical dynamic model investigating the short-term cellular kinetics induced by riddelliine, a hepatic endothelial carcinogen.

In recent studies, riddelliine, a pyrrolizidine alkaloid, was found to increase rates of replication and apoptosis and induce hemangiosarcoma in the liver of rats and mice. To analyze DNA replication and apoptosis data taken from the same animals, we have developed a predictive mathematical model for describing BrdU labeling and apoptotic processes. The model allows the incorporation of simple diurnal patterns in cellular kinetics and is applied to data on hepatocytes and endothelial cells taken from riddelliine exposed rats. Predictions from the model were used with multivariable nonlinear regression techniques to estimate replication and apoptotic rate constants for both cell types and all treatment groups. Hypothesis tests were used with the predicted rates to separate the competing effects of riddelliine on replication and apoptosis of hepatocytes and endothelial cells as well as compare replication rates between cell types. That estimated replication rates were found to be significantly higher for endothelial cells supports the supposition of induction of hemangiosarcoma by riddelliine in the liver.