Induction of maternal toxicity in the rat by dermal application of retinoic acid and its effect on fetal outcome.

Time-mated Sprague-Dawley rats were administered all-trans-retinoic acid (RA) dermally on gestational days 11 through 14 at three dosage levels (25, 100, and 250 mg/kg body weight). Dams administered ethylenethiourea (ETU) dermally on gestational days 11 to 12 or RA orally on day 12 were used to indicate the strain's sensitivity to teratogenesis. The chemicals were dissolved in dimethylsulfoxide (DMSO) for dermal application or suspended in corn oil for treatment by gavage. The maternal weight gain, pup weight, number of resorptions and number of fetuses with gross malformations, and skeletal/organ-level anomalies were determined. Beginning with day 15, dams dermally treated with RA exhibited dermal lesions at the site of application, most dams showed vaginal bleeding by day 16, and approximately 20% did not survive to day 19. Relative to the DMSO control group, maternal weight gain in the dermal RA groups was decreased by approximately 50% at the lowest dose, with essentially no weight gain at the intermediate- and high-dose levels. The decrease in average fetal weight at the two higher doses was significant, whereas the resorption and malformation frequencies were not significantly increased by dermal treatment with RA. Without significantly affecting fetal weight or resorption frequency, dermal application of ETU significantly increased the frequency of skeletal anomalies, primarily tail defects. Oral administration of RA did not increase the malformation frequency nor produce significant maternal or fetotoxic effects. In summary, treatment of pregnant Sprague-Dawley rats by dermal application of RA dissolved in DMSO resulted in significant toxicity to the dam.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphological and biochemical studies of a naturally occurring enteropathy in the Irish setter dog: a comparison with coeliac disease in man.

A naturally occurring enteropathy was identified in Irish setter dogs and wheat-sensitivity was demonstrated in a litter bred from two of the affected animals. The morphological and biochemical features of this enteropathy are described and compared to coeliac disease in man. Affected animals comprised 10 dogs that presented with poor weight gain or weight loss, with or without diarrhoea. Exocrine pancreatic function was normal and culture of duodenal juice demonstrated no marked bacterial overgrowth. Serum vitamin B12 concentrations were unaltered, but in some cases low serum and erythrocyte folate concentrations and reduced xylose absorption provided indirect evidence for proximal small intestinal disease. Examination of peroral jejunal biopsies revealed patchy morphological changes within individual animals, comprising predominantly partial, but in one case subtotal, villous atrophy. Brush border enzymes were selectively altered: the specific activities of alkaline phosphatase, leucyl-2-naphthylamidase and of zinc-resistant alpha-glucosidase were reduced by approximately 40 per cent, while activities of maltase, sucrase, lactase and gamma-glutamyl transferase were unaltered. Activity of a lysosomal enzyme was increased and there was evidence for enhanced lysosomal fragility. The activity of malate dehydrogenase, with a dual mitochondrial and cytoplasmic localisation, was decreased but there were no changes in the activities of marker enzymes for basal-lateral membranes, endoplasmic reticulum or peroxisomes. These findings, particularly the specific biochemical abnormalities, were comparable to those in partially treated coeliac disease in man; however, a specific role for wheat in the pathogenesis of the disease has yet to be defined.

Wheat-sensitive enteropathy in Irish setter dogs: possible age-related brush border abnormalities.

The pathogenesis of a wheat-sensitive enteropathy was explored in a litter bred from two Irish setters with a naturally occurring enteropathy. Jejunal biopsies from all eight progeny exhibited morphological changes comparable to those in the parents, while biochemical abnormalities appeared to be related to age. In biopsies obtained from the first group of four dogs at eight months, the activities of alkaline phosphatase and of leucyl-2-naphthylamidase were almost undetectable while disaccharidases were unaltered. In contrast, analytical subcellular fractionation of biopsies obtained from the second group of four dogs at nine months showed that specific activities now reflected a major deficiency of brush border alkaline phosphatase, and normal brush border leucyl-2-naphthylamidase accompanied by elevated soluble activity. Further studies are indicated to determine whether these findings represent an age-related abnormality affecting specific microvillus membrane proteins.

Bacterial overgrowth associated with a naturally occurring enteropathy in the German shepherd dog.

Quantitative and qualitative bacteriological studies were performed on duodenal juice from 19 dogs with chronic small intestinal disease. Bacterial overgrowth was demonstrated in seven German shepherd dogs with minimal histological but specific biochemical abnormalities in the jejunal mucosa. Most frequently this overgrowth comprised bacteria of the normal flora, particularly Escherichia coli and enterococci, but these were occasionally accompanied by bacteria rarely present in the proximal small intestine of the normal dog, particularly Clostridium species. In most cases this overgrowth was associated with raised serum folate and reduced serum vitamin B12 concentrations, a finding consistent with the capacity of many enteric bacteria to synthesise folate and bind vitamin B12.

Is measurement of transportability class of inhaled material by in vitro dissolution satisfactory?

Much of the published data on in vitro dissolution of uranium is based on the batch replacement technique. Recent papers have suggested that this technique, though convenient, may produce results that are determined more by the experimental design than by the transportability (solubility) of the material being tested. Re-examination of some of the published data appears to support this suggestion.

Transportation of radioactive material in Georgia.

A 3-yr study of radioactive materials transportation examined the magnitude of radioactive materials shipments in terms of numbers of packages and motor vehicle trips and types of materials; compliance with regulations for packaging, labelling, handling, external radiation exposure, and surface contamination; and dose to workers as measured with personnel dosimeters. Much of the information was obtained at the Atlanta airport and its vicinity, a package distribution center for the southeastern U.S., and at the Barnwell, S.C. radioactive waste burial site, the destination of most shipments of radioactive waste from or through Georgia. Approximately 12,000 packages in radioactive material categories I, II and III were handled in Georgia each year. Motor vehicles made approximately 3300 trips per year. Some instances of noncompliance were observed, but few of them had the potential for elevated radiation exposure of persons. Several incidents associated with radioactive material transport are reported, of which one may have resulted in slightly elevated exposures to persons. Among drivers and handlers who worked with radioactive material shipments, dosimeters showed that less than one-half of them received radiation doses above background levels. The highest doses were found for drivers who transported large numbers of 99Mo generators.

Compliance and policy issues and recommendations related to revision of the National Interim Primary Drinking Water Regulations for Radionuclides.

This paper summarizes the deliberations and conclusions of the Compliance and Policy Committee of the National Workshop for Radioactivity in Drinking Water. Prior to and during the workshop the committee considered a total of 32 possible compliance and policy issues and determined that 22 were valid. The committee developed positions on seven of these and these positions are presented herein. The remaining 25 issues are also listed with the committee's evaluation of each.

Power reactor health physics in the 1960s.

This note is a personal re-collection of some of the problems and experiences of the Health Physics Department staff at Dungeness Power Station during the period 1963-1971. This was a period of construction, commissioning, operating and learning. It was an interesting period for power reactor health physicists as appropriate instrumentation; information and experience were all in fairly short supply.

Discrete event simulation of patient admissions to a neurovascular unit.

Evidence exists that clinical outcomes improve for stroke patients admitted to specialized Stroke Units. The Toronto Western Hospital created a Neurovascular Unit (NVU) using beds from general internal medicine, Neurology and Neurosurgery to care for patients with stroke and acute neurovascular conditions. Using patient-level data for NVU-eligible patients, a discrete event simulation was created to study changes in patient flow and length of stay pre- and post-NVU implementation. Varying patient volumes and resources were tested to determine the ideal number of beds under various conditions. In the first year of operation, the NVU admitted 507 patients, over 66% of NVU-eligible patient volumes. With the introduction of the NVU, length of stay decreased by around 8%. Scenario testing showed that the current level of 20 beds is sufficient for accommodating the current demand and would continue to be sufficient with an increase in demand of up to 20%.