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Biomedical subjects

W C Thomas

Publications and source records attributed to W C Thomas.

At least 19 recordsLinked to original sources
PubMed1995

Comparison of the maximum tolerated dose (MTD) dermal response in three strains of mice following repeated exposure to acrylic acid.

The dermal response of three strains of mice (ICR, C3H and B6C3F1) exposed to repeated doses of 0, 1 or 4% acrylic acid was examined over 13 wk. Microscopic and gross changes to the skin were classified as being indicative of exceeding the maximum tolerated dose (MTD), reaching the MTD, or tolerating the dose based on proposed MTD guidelines established in US Environmental Protection Agency (EPA) Workshops on dermal carcinogenesis bioassays. A significant number of animals in all three strains with repeated exposure to 4% acrylic acid experienced skin irritation that was classified as having reached or exceeded the MTD compared with animals exposed to either 1% acrylic acid or the 0% acrylic acid acetone control. These results were observed within the first 3 wk of exposure, but there was some accommodation to irritation by 8 wk of exposure. Microscopic findings provided a more sensitive index for exceeding MTD than gross observations taken only at autopsy, but generally correlated well for MTD if gross observations were taken at regular intervals during treatment. That is, to set MTD, gross observations could be used if taken over the entire course of the exposure, but using microscopic findings was generally a more reliable or sensitive measure. EPA guidelines suggest that it is inappropriate to conduct a dermal bioassay at concentrations that exceed the MTD. Acrylic acid at 4% in acetone clearly exceeded the MTD based on microscopic or gross observation criteria. At 4%, strain differences were evident by gross observation only, with the ICR strain being less susceptible to irritation than C3H or B6C3F1 strains. These strain differences were not apparent with microscopic examination. Acrylic acid at 1% in acetone, although demonstrating signs of minimal irritation, was fairly well tolerated by all mice in all strains. Thus, acrylic acid at 1% in acetone, one-quarter of the concentration that was in clear excess of the MTD, would be the appropriate dose concentration for lifetime skin studies based on MTD criteria.

Acrylates↗
PubMed1994

Exercise, age, and bones.

Skeletal development in average healthy individuals is maximal at age 25 in women and at age 30 to 35 in men. However, there are significant racial differences, skeletal mass being greater in black than in white individuals. This difference appears best accounted for by increased muscle mass in blacks. Bed rest, immobilization, weightlessness (as in space flights), and aging induce a decrease in skeletal mass. The degree of osteopenia in the elderly depends partly on skeletal development during formative years and can be prevented from becoming severe by maintaining good nutritional status (calcium, vitamin D, protein) and physical activity. Maintenance or actual increase in muscle mass is a desired effect of appropriate physical activity, but excessive physical exercise may induce estrogen deficiency and menstrual irregularities in premenopausal women. In addition to diet and exercise, pharmacologic therapy (estrogens, androgens, diphosphonates, or calcitonin) is indicated in patients with significant osteoporosis.

Absorptiometry, Photon↗
PubMed1992

Genetic toxicology of acrylic acid.

Acrylic acid was tested for gene mutations in the in vitro CHO/HGPRT assay, for chromosome aberrations in CHO cells in culture, and for potential to induce unscheduled DNA synthesis in rat hepatocytes in culture. In vivo assays performed included the Drosophila sex-linked recessive lethal assay by both the feeding and injection routes, the in vivo cytogenetic assay in rat bone marrow cells after both a 1-day and 5-day oral dosing regimen, and a dominant lethal assay in mice by both an acute and 5-day dosing regimen. All results were negative (non-mutagenic) except for the in vitro chromosome aberration assay. This latter result is consistent with the previously reported possible clastogenic activity suggested by the results of the mouse lymphoma L5178Y TK locus assay in which a predominance of small-colony mutants was observed (Moore et al., Environmental and Molecular Mutagenesis 1988, 11, 49-63). The rapid clearance of acrylic acid in animals and the weight of evidence of genetic toxicity testing, including negative in vivo data in both somatic and germ cells, indicate a lack of genetic toxicity of acrylic acid in vivo.

Acrylates↗
PubMed1991

Subchronic oral toxicity of cellulose acetate in rats.

Cellulose acetate was administered by way of a dietary admixture to Sprague-Dawley rats (20/sex/group) at dose levels of 0, 500, 2500 and 5000 mg/kg body weight/day for 94-96 days. Physical observations, body weight and food consumption measurements were made before testing and throughout the study. Ophthalmoscopic examinations were conducted on all animals before testing and just prior to study termination. Haematology, clinical chemistry and urinalysis were performed at 1.5 and 3 months on 10 animals/sex/group. After 3 months of treatment the animals were killed, terminal body weights and organ weights were measured and ratios calculated. Histopathological examination of tissues from the control and high-dose groups was conducted. The evaluation of physical observations, ophthalmology, body weight, food consumption, haematology, clinical chemistry, organ-to-body-weight ratios, gross pathology and histopathology revealed no evidence of an adverse effect related to treatment with cellulose acetate.

Administration, Oral↗
PubMed1991

Acute inhalation toxicity studies in several animal species of an ethylene oxide/propylene oxide copolymer (UCON 50-HB-5100).

An acute inhalation toxicity study in several species of animals with an ethylene oxide/propylene oxide copolymer (EO/PO) having a molecular weight of 4000 [UCON-50-HB-5100, CAS #9038-95-3] was designed to determine if any species variation could be shown. Species tested included: rats, mice, hamsters, guinea pigs, and dogs. The test material was administered as a respirable liquid aerosol for 4 hours at target concentrations of 50, 100, 200, and 500 mg/m3. A vehicle control group was exposed to a distilled water aerosol. The 4 hours LC50's were calculated to be 147 mg/m3 [rats], 174 mg/m3 [mice], 293 mg/m3 [guinea pigs] and 511 mg/m [hamsters]. The dog LC50 was determined to be greater than 500 mg/m3 since all the test animals survived exposure to this concentration. These values show that rats and mice were the most sensitive species with a declining response in guinea pigs, hamsters and dogs. Lung weights were increased at all exposure concentrations in rats, mice and hamsters. Lung weights were increased in guinea pigs at exposure concentrations of 100 mg/m3 and above. Lung weights in dogs were increased only at the 500 mg/m3 exposure concentration. Significant pathological changes were limited to the lungs and were more common in animals which died prior to scheduled sacrifice. Grossly, these lung changes consisted of red discoloration, edema, emphysema, and surface irregularities. Microscopic findings in the lungs included acute congestion and hemorrhage and, less commonly, acute interstitial inflammation.

Administration, Inhalation↗
PubMed1990

The effect of hypoparathyroidism on the aging skeleton.

Serum concentrations of parathyroid hormone are frequently increased in elderly subjects. How much this increase may contribute to the development of osteoporosis in such subjects is unknown. Long-standing hypoparathyroidism has been reported to be accompanied by an increase in skeletal density. In seven consecutive women, aged 40 to 83 years, with hypoparathyroidism of at least 18 years duration, the mineral density in the lumbar vertebrae was measured by quantitative computed tomography (QCT) and dual photon absorptiometry (DPA). In these subjects, the bone mineral density by dual photon absorptiometry was 1.4 to 6.2 standard deviations above mean values for age-matched normal women. However, the mineral density of vertebral trabecular bone as determined by quantitative computed tomography was only slightly increased above values reported for normal women. The differences between the values determined by dual photon absorptiometry and quantitative computed tomography indicate that most of the increase in mineral density was a reflection of increased cortical bone. Roentgenograms of the metacarpals did not reveal consistent differences between normals and the hypoparathyroid subjects. These findings suggest the possibility that control of parathyroid function might be of value in treating osteoporotic patients.

Absorptiometry, Photon↗
PubMed1990

Urinary calculi in hypercalcemic states.

In this brief review of various hypercalcemic disorders and the likelihood of renal calculus formation, it is clearly evident that renal calculi occur much more often in hyperparathyroidism than in the other hypercalcemic states. Dystrophic calcification and nephrocalcinosis are common to all of the hypercalcemic disorders, including hyperparathyroidism, when the hypercalcemia is marked and the limit of solubility of calcium and phosphate in serum is approached. Interestingly, in sarcoidosis there are calcium oxalate crystals in variously distributed sarcoid granuloma, and the renal calculi are composed of calcium oxalate. By contrast, in hyperparathyroidism, the calculi composed of calcium phosphate predominate. This indicates a subtle and as yet undefined alteration in oxalate metabolism in sarcoidosis. An increase in urine pH occurs in hyperparathyroidism, and this enhances formation of crystalline calcium phosphate. However, the striking disparity between the frequency of calculus formation in hyperparathyroidism and that in other hypercalcemic disorders, several of which may be of relatively long duration, suggests that there indeed may be increased promoters of crystal formation in the urine of hyperparathyroid patients.

Diagnosis, Differential↗
PubMed1989

Vitamin D deficiency in Florida, the Sunshine State.

Several years may be required for development of clinically evident osteomalacia in previously healthy subjects deprived of exposure to sunlight or enriched dietary sources of vitamin D. In a survey of residents of a 120 bed VA nursing home who had been patients there for two to six years, 17 were found to have x-ray or laboratory findings suggestive of the presence of vitamin D deficiency. Bone biopsy in eight of these 17 patients revealed definite osteomalacia in three patients. Thus, vitamin D deficiency may develop in confined, nonvitamin D fortified patients in Florida just as in more northern climes. Daily exposure for 30 minutes to sunshine or oral administration of 2.5 mg of vitamin D2 or D3 twice yearly has been recommended to prevent deficiency of this vitamin.

Aged↗
PubMed1988

Extracorporeal shock-wave lithotripsy: prevalence of renal stones 3-21 months after treatment.

One hundred and four (70%) of the first 148 patients who underwent extracorporeal shock-wave lithotripsy (ESWL) at the University of Florida were evaluated for persistent or recurrent renal stone disease. Radiographs obtained 3-21 months after treatment showed that 53 (50%) of 106 treated kidneys were free of stones. In 48 of the 53 kidneys that contained stones, the stones were residual fragments dating from the period immediately after ESWL. New stones had developed in only five kidneys. The 50% incidence of stone-free kidneys 3-21 months after ESWL is less than the 65-90% rate reported by other institutions in the United States and Europe. After stone removal by ESWL, new stone formation occurs at a rate of 5%, which is much lower than the expected recurrence rate of 37-50%.

Follow-Up Studies↗
PubMed1988

Extracorporeal shock-wave lithotripsy: long-term complications.

Of 148 patients who had extracorporeal shock-wave lithotripsy (ESWL) for renal lithiasis in 1984, 21 (14%) returned after 17-21 months for renal function tests (21 patients) and blood pressure determination (20 patients). Quantitative radionuclide renography showed a statistically significant (p = .048) decrease in the percentage of effective renal plasma flow (ERPF) to the treated kidney. Two of these patients had developed hypertension requiring treatment but became normotensive when given medication. In the other patients there was a statistically significant increase in both systolic (p = .0002) and diastolic (p = .015) blood pressures. Information about blood pressure was also obtained from an additional 71 (48%) of the 148 patients; of the total 91 patients (61%) in whom blood pressures were obtained, seven (8%) had developed sufficiently severe hypertension to require treatment beginning within 21 months after ESWL. Side effects of ESWL for renal lithiasis include hemorrhage, edema, and acute tubular necrosis of the kidney. This form of renal trauma is associated with an immediate decrease in renal function of the treated kidney, and this decrease may be permanent. ESWL is also associated with the onset of hypertension, which may occur immediately or be delayed by several weeks or months. Although the pathogenesis remains unknown, hypertension is an important complication of ESWL in about 8% of patients.

Adult↗
PubMed1987

Inhalation teratology studies of n-butyl mercaptan in rats and mice.

n-Butyl mercaptan (n-BM) is used as a solvent and a chemical intermediate. Pregnant Charles River CD-1 mice and COBS CD rats were randomly assigned to a control group and to three n-BM-exposed groups of 25 rats and 25 mice each. The animals were exposed by whole-body inhalation to mean n-BM concentrations of 10, 68, or 152 ppm on a 6-hr daily exposure schedule. Rats were exposed on Gestation Days 6-19 and mice on Gestation Days 6-16. The control group was exposed to filtered air only on a comparable regimen. Cesarean sections were performed on all surviving mice on Gestation Day 17 and on all rats on Gestation Day 20. Seventeen of the n-BM-treated mice died: 8 at the 68-ppm level and 9 at the 152-ppm level; none of the n-BM-treated rats died. An increased postimplantation loss and increased early resorption occurred in mice exposed at 68 and 152 ppm, indicating embryotoxicity. An increased incidence of cleft palate was observed in mice exposed to 10 or 68 ppm which was not statistically significant. Total fetal abnormalities were statistically significantly different from controls at 68 ppm where maternal lethality was observed when based on the fetal unit although not when based on the litter unit. Rats exposed to 152 ppm or less demonstrated no terata.

Abnormalities, Drug-Induced↗
PubMed1986

Influence of aluminum on mineralization during matrix-induced bone development.

A model of de novo mineralization employing matrix-induced endochondral bone formation in rats was used to study the short-term effects of aluminum on the deposition of calcium and phosphate in vivo. In experiments where systemic aluminum concentrations were elevated, the cellular processes associated with bone development appeared to be normal, if somewhat delayed, however precipitation of the mineral phase was prevented. This suggests a primary direct physical chemical effect of aluminum in vivo on calcification, as suggested by in vitro studies which demonstrate that aluminum is a potent inhibitor of calcium phosphate precipitation. Aluminum salts implanted locally with the matrix appeared to be toxic to the cellular processes leading to chondrogenesis and osteogenesis.

Alkaline Phosphatase↗