Cell-specific transcription of the smooth muscle gamma-actin gene requires both positive- and negative-acting cis elements

We recently labeled with carbon-11, a high affinity, selective, 5-HT3 receptor (5-HT3R) ligand, S21007, for potential positron emission tomography (PET) applications. To evaluate the in vivo binding properties of [11C]S21007, its brain regional distribution, tissue and plasma pharmacokinetics and plasma metabolisation were characterized. To circumvent the problem of highly discrete brain localization of the 5-HT3R (area postrema, hippocampus), we designed an original approach combining high-resolution imaging techniques (ex vivo phosphor plate autoradiography and MRI-guided coronal PET in the rat and baboon, respectively). After i.v. injection of trace amounts of [11C]S21007 to rats, phosphorimager autoradiography failed to reveal in vivo specific binding to, nor selectivity for 5-HT3R-rich areas. PET studies in the baboon showed consistent results, i.e., there was no selective accumulation of [11C]S21007 in the area postrema or hippocampus, and neither displacement nor presaturation with cold S21007 resulted in significant changes in tissue distribution or kinetics of [11C]S21007.     

Artemisinin-derived sesquiterpene lactones as potential antitumour compounds: cytotoxic action against bone marrow and tumour cells

Epidemiologic and public health researchers frequently include several dependent variables, repeated assessments, or subgroup analyses in their investigations. These factors result in multiple tests of statistical significance and may produce type 1 experimental errors. This study examined the type 1 error rate in a sample of public health and epidemiologic research. A total of 173 articles chosen at random from 1996 issues of the American Journal of Public Health and the American Journal of Epidemiology were examined to determine the incidence of type 1 errors. Three different methods of computing type 1 error rates were used: experiment-wise error rate, error rate per experiment, and percent error rate. The results indicate a type 1 error rate substantially higher than the traditionally assumed level of 5% (p < 0.05). No practical or statistically significant difference was found between type 1 error rates across the two journals. Methods to determine and correct type 1 errors should be reported in epidemiologic and public health research investigations that include multiple statistical tests.     

An outbreak of needlestick injuries in hospital employees due to needles piercing infectious waste containers

OBJECTIVES: To investigate the cause of an outbreak of needlestick injuries (NSIs) in hospital employees. SETTING: A 700-bed university hospital. DESIGN: Outbreak investigation, laboratory evaluation of a medical waste disposal device, cost analysis. METHODS: Employee health department records were reviewed of workers suffering sticks from needles piercing fiberboard-contaminated material containers (CMCs). A laboratory evaluation of needle-puncture resistance properties of the CMCs was performed using a testing apparatus. The cost of a hospital waste disposal program using fiberboard CMCs was compared with the cost of a program using rigid plastic (polypropylene) boxes. RESULTS: During 40 months of surveillance in 1986 and from 1989 to 1991, only one NSI had occurred from a needle piercing a CMC. During 9 months in 1993, 13 NSIs occurred due to needles piercing CMCs (P < .001). No clinical illness resulted from the NSIs. The outbreak was halted by a temporary change to plastic (polypropylene) boxes for sharps disposal ($4.92 to $23.33/cu ft) until receipt of a box with a newly designed solid fiberboard liner ($1.25/cu ft). CMC liners used during the epidemic had a mean needle puncture resistance of 527 g, as compared with 660 g for liners used before the outbreak (P < .001). The new solid fiberboard liner has a mean puncture resistance of 1,765 g. A program of waste disposal using fiberboard CMCs was found to cost approximately one-seventh the cost of a program using plastic boxes for disposal of infectious waste. CONCLUSION: A program for infectious waste disposal using fiberboard CMCs can be safe and cost-effective if appropriate standards for puncture resistance are met.     

Cross-form priming in normal aging and in mild dementia of the Alzheimer type

Twenty patients at early stages of Alzheimer's disease (AD), 20 elderly control subjects and 20 young subjects completed a cross-form priming task, followed by a free recall task. Results show that patients with mild AD display priming effects, and that these priming effects are strictly comparable to those obtained by elderly and young control subjects. Moreover, while the patients' performances are normal in the implicit part of the task, they are massively impaired in the explicit free recall task. These results don't support the hypothesis of a dissociation of performances between identification tasks and generation tasks in Alzheimer's disease, and show that conceptual priming can be observed at early stages of the disease, despite semantic memory impairments.     

Secondary prevention of coronary heart disease

Despite the significant reduction in cardiovascular mortality during the past three decades, atherosclerotic coronary heart disease (CHD) remains the leading cause of death and disability in the United States. Randomized clinical trials in patients with CHD have provided convincing evidence that risk factor modification is beneficial in decreasing all-cause mortality and cardiovascular morbidity and mortality. Multifactorial coronary risk reduction provides the most substantial benefit. Coronary risk reduction is associated with a decrease in cardiovascular-related hospital admissions, a reduced need for myocardial revascularization procedures, and an improved quality of life for the patients so treated. Control of coronary risk factors is an integral component of the optimal care of the patient with CHD.     

Non-C282Y familial iron overload: evidence for locus heterogeneity in haemochromatosis

Haemochromatosis (HC) is an autosomal recessive disease with progressive iron overload leading to midlife onset of clinical complications. The causal gene (HFE) maps to 6p, in close linkage with the HLA class I genes. An HFE candidate gene recently identified has two missense mutations (C282Y and H63D) associated with the disease. Here we document the phenotypic and genetic analysis of a nuclear family comprising two sibs with symptomatic and massive iron overload before the age of 25. The disease seemed to be recessively transmitted and fitted the agreed criteria for haemochromatosis, but was neither associated with the C282Y and H63D mutations nor linked with HLA markers. Our data strongly support locus heterogeneity in haemochromatosis by showing evidence that the gene responsible for juvenile haemochromatosis (JH) does not map to 6p. In the absence of clear cut phenotypic distinction from typical haemochromatosis, patients below 30 years of age and C282Y negative should be considered as putative juvenile cases. This has practical implications in genetic counselling and family management.