Osteoporosis and bone morbidity in cardiac transplant recipients.

PURPOSE: To evaluate the incidence and etiology of osteopenia and pathologic fractures in cardiac transplant recipients. PATIENTS: Thirty-one adult male cardiac transplant recipients and 14 adult men with congestive heart failure (CHF) awaiting cardiac transplantation. METHODS: Assessment of indices of bone and mineral metabolism and of bone mineral density (BMD) by dual-energy x-ray absorptiometry. RESULTS: BMD in the proximal femur was below normal in both groups compared to that in age-matched control subjects, whereas BMD in the lumbar spine was normal. There was no significant difference in BMD at any site between the two groups. No clinical parameter predicted BMD. In all patients, laboratory indices of bone mineral metabolism, except parathyroid hormone (PTH) levels, were normal and not statistically different between the two groups. CHF patients had a trend toward elevations of PTH, 1,25-dihydroxyvitamin D, and urinary calcium excretion compared to transplant patients. Eight of 31 transplant patients and 2 of 14 CHF patients had vertebral compression fractures (c2 = 11.8, p < 0.0006). Transplant recipients with fractures had twice as many rejection episodes as did transplant patients without fractures, but did not differ in cumulative dose of steroids. Two patients developed avascular necrosis of the femoral head following transplantation. CONCLUSIONS: Cardiac transplant recipients and patients with CHF awaiting transplantation had decreased hip BMD, but normal spine BMD. Although immunosuppressive therapy did not appear to influence bone mass, loop diuretics prior to transplantation may have stimulated a mild secondary increase in PTH that could have differentially caused loss of bone density at the hip in both groups. Pulse corticosteroids used in treating rejection may have contributed to the increased incidence of vertebral fractures in transplant patients. These data suggest that severe CHF with its associated diuretic use and decreased activity are primary contributors to osteopenia in these patients.

Developmental variation of the diaphragm and liver in Fischer 344 rats.

The nature and frequency of a developmental variation of the diaphragm and liver in Fischer 344 rats are described. Totals of 20, 98 and 55 (25 for caesarean-sectioning and 30 for natural delivery) mated female rats were used for Experiments 1, 2, and 3, respectively. Each rat was intubated (gavage) with either an aqueous suspension of 0.2% METHOCEL, 0.25% methyl cellulose, or distilled water as a single daily dose from days 6 through 15 (inclusive) of gestation. On the 20th day of gestation, a caesarean-section was performed, and the uterine contents of each rat were examined. A gross necropsy was performed on the pups of 30 mated female rats on day 21 postpartum. The visceral examinations conducted on these fetuses and pups included an evaluation of a developmental variation in the diaphragm and liver. The variation consisted of a thin fibrous central tendon of the diaphragm with an area of liver (0.5-3 mm diameter) that protruded within the thin central tendon of the diaphragm. The incidence (mean % of fetuses affected per litter) of the diaphragm/liver developmental variation was 9% and 11% for METHOCEL- and water-treated groups, respectively. A thin central tendon was present in the diaphragm of all fetuses of methyl cellulose-treated dams; these fetuses did not have a raised area of the liver present within the diaphragm's central tendon. However, in a few weaned pups of the Fischer 344 rats in this study, liver protruded within the central tendon of the diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)

Palatability studies of snail and slug poison baits, using dogs.

In 1975, the California Department of Food and Agriculture required registered manufacturers of snail and slug baits to present data showing the unattractiveness of these products to dogs, in order to reduce the number deaths in dogs due to poisoning by eating these baits. A cooperative project involving the University of California, the California Department of Food and Agriculture, and the snail and slug bait manufacturers was designed to assist the manufacturers in assessing the palatability of their products by dogs and to develop criteria for the regulatory agencies to use to ensure that the products they were registering were unattractive to dogs. The studies showed that most recently formulated baits were relatively unpalatable for dogs. A 2-panel consumption testing procedure was developed and is being used by the California Department of Food and Agriculture and the Environmental Protection Agency as criteria for registration. Current reports indicate a dramatic decrease in snail and slug bait poisonings in California after these criteria were established as requirements for registration of snail and slug baits.

Hexachlorobenzene II. Effects on growing lambs of prolonged low-level oral exposure to hexachlorobenzene (HCB).

Fifty growing male (castrated) lambs were exposed to hexachlorobenzene in the diet at levels of 0, 0.01, 0.1 and 1.0 ppm for 90 days. They were then moved to clean quarters and the study continued for an additional 210 days. Growth rates, certain plasma enzyme activities and hepatic microsomal enzyme activities were studied to detect subclinical effects related to the exposure. A 19-day acute exposure at 100 ppm was done and the same parameters except for growth rate, measured. Hematocrit and plasma protein concentrations were also monitored. No significant changes were seen in the growth rates (90 days exposure), in the plasma enzymes alkaline phosphatase, glutamic oxaloacetic transaminase, glucose 6-phosphate dehydrogenase or succinic dehydrogenase, or in the hematocrit or plasma protein concentrations after either the 90-day or 19-day exposures. However, in vivo metabolism of antipyrine was increased in both the 1.0 ppm (90-day) and the 100 ppm (19-day), but was significantly increased (p less than 0.01) in only the 100-ppm exposure. Additionally, hepatic microsomal N-demethylase was increased significantly by the 90-day exposure at 1.0 ppm and the 19-day exposure at 100 ppm, but the hepatic microsomal O-demethylase was significantly increased only after the 1.0-ppm exposure. Histopathologic examination of tissues (brain, lung, myocardium, large and small intestines, liver, kidneys, adrenals, mesenteric lymph nodes) collected from animals sacrificed at 90 days and at the termination of the study (300 days) revealed no lesions suggestive of harmful HCB exposure.

Hexachlorobenzene I. Uptake, distribution and excretion of hexachlorobenzene (HCB) in growing lambs.

The uptake, distribution, and excretion of hexachlorobenzene (HCB) was studied in young male (castrated) lambs. Lambs were exposed for 90 days at a dietary concentration of 0, 0.01, 0.1 and 1.0 ppm. Tissue concentration of HCB were monitored by periodic omental biopsy and by post-slaughter collection of tissues at 90 and at 300 days. Blood samples were collected by venipuncture each time that biopsies or sacrifice occurred. Findings of the 300 days duration study were: (1) the growth rate of the exposed lambs was unaffected by the exposure to the dietary HCB, (2) adipose tissue concentrations reached a level approximately ten times that in the diet at the end of the 90-day exposure period, (3) HCB concentration was higher in the omental fat than in the perirenal fat at 90 days but not at 300 days, (4) a good portion of the apparent decresae in HCB in the fat following cessation of exposure is due to dilution (by increasing carcass fat), (5) the apparent half-life of HCB was approximately 90 days and was not dose-dependent at the exposure rates studied, and (6) the highest HCB concentrations in other tissues were in the brain and liver. The study demonstrated that the omental biopsy provides an excellent means of estimating body fat burden of this lipid soluble pesticide, although it tends to provide an overestimate during actual dietary exposure. The finding that the bioconcentration of and the depletion from the adipose tissues were independent of dose enables prediction of the degree to which food animals might become contaminated if allowed to feed on HCB-contaminated pastures or feed stuffs, and of the time which will be required for such residues to decrease to negligible levels. This predictive ability is of obvious benefit to both the food animal producer and the consumer. Since the HCB is apparently much more stable in the body than is indicated by the depletion half-life of 90 days in these growing lambs, it follows that environmental contamination of grazing lands or animal feeds is of far greater consequence for adult animals which would not be likely to experience the growth dilution of carcass residues.