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Biomedical subjects

D A Willigan

Publications and source records attributed to D A Willigan.

14 recordsLinked to original sources
PubMed1998

Acute, subchronic, and chronic toxicity studies with felbamate, 2-phenyl-1,3-propanediol dicarbamate.

Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is a novel anticonvulsant that is effective against both chemically and electrically induced seizures in laboratory animals. Acute, subchronic, and chronic studies were conducted in mice, rats, and dogs to establish a preclinical safety profile for this drug. Clinical signs following single intraperitoneal doses included hypoactivity, tremors, decreased muscle tone, ataxia, prostration, and labored breathing. Death was observed after intraperitoneal but not oral administration. A consistent drug-related effect noted in all multiple-dose studies with this compound was decreased body weight and food consumption. The only other consistent change noted in multiple-dose studies with felbamate was an increase in liver weight (relative and absolute) in the rat and dog which was accompanied in some cases by increases in serum enzyme levels. No histopathological changes were observed in the liver that could explain these elevated serum enzyme levels. Based on the results of these studies it was concluded that long-term administration of felbamate in human clinical trials was warranted.

Administration, Oral↗
PubMed1985

Comparison of the sensitivity of the vaginal mucous membranes of the albino rabbit and laboratory rat to nonoxynol-9.

Studies were conducted to compare the sensitivities of the vaginal mucous membranes of the albino rabbit and albino rat to irritation by the surfactant nonoxynol-9. The purpose of this comparison was to evaluate the rat as a model for screening vaginal products for their potential irritancy. Nonoxynol-9 at various concentrations in distilled water was administered intravaginally by lavage once a day for four consecutive days. On day 5, the animals were killed and the vaginal tissues were processed and examined histopathologically. Using a predetermined semiquantitative scoring system, it was found that the intensity of irritation was concentration dependent in both species. In the rabbit, the irritation was significantly greater than that in the rat, being mild with concentrations of 2.5 and 5% and moderate to severe at 12.5 and 25%. In the rat, irritation was negligible up to 12.5%, becoming mild at 25% and more moderate at 75%. Thus the vaginal mucosa of the rabbit is more sensitive than that of the rat and may be expected to give a more exaggerated representation of the irritation potential of a compound to the human vagina than would the rat mucosa.

Animals↗
PubMed1982

pH and the potential irritancy of douche formulations to the vaginal mucosa of the albino rabbit and rat.

Studies were conducted to determine the effect of the pH of a vagina douche on its irritation potential for the vaginal mucosa of the albino rabbit and albino rat. The pH of a liquid douche formulation was varied by modification of the lactic acid/sodium bicarbonate ratio and the resulting preparations were administered intravaginally by lavage once a day for four consecutive days. On day 5, the animals were killed and the vaginal tissues were processed and examined histopathologically. Using a predetermined semiquantitative scoring system, it was not in the rat. As the pH was decreased, the degree of irritation became more severe in the rabbit; at pH 3.0 and below, irritation was sufficiently severe for the formulation to be considered unacceptable for human use. Only minimal irritation was seen in the rat at any of the pH levels dependent below 3 . 0. This exaggerated response must be taken into consideration when the rabbit is used for assessing the vaginal-irritation potential of douches. The rabbit, having a vaginal mucosa more sensitive than that of the rat, remains an appropriate model for measuring the potential irritancy of new douche products, because comparisons can be made with products of known irritancy.

Animals↗
PubMed1981

Cancer induction following single and multiple exposures to a constant amount of vinyl chloride monomer.

Vinyl chloride monomer (VCM), already identified as a human animal carcinogen, was selected as a model agent to explore an area of concern for single and intermittent low level exposure. In traditional cancer bioassay, animals are repeatedly exposed over their lifespan to a dose of suspected chemical. In the current studies rats and mice were exposed in an inhalation chamber to single one-hour doses of VCM ranging from 50 to 50,000 ppm. A second group was given 10 one-hour exposures to 500 ppm or 100 one-hour exposures to 50 ppm of the same chemical. All animals were then observed for the remainder of their lives, generally 18-24 months. Moribund animals were euthanized, and survivors were sacrificed on schedule and their tissues examined for pathological changes. Specifically, the oncogenic study demonstrated dose related effects for single one-hour exposure of VCM at high levels, i.e., 5,000 and 50,000 ppm. These concentrations increased the incidence of pulmonary adenomas and carcinomas in mice. Repeated exposure of A/J mice to the same chemical at 500 ppm X 10 one-hour exposures also increased the incidence of pulmonary adenomas and carcinomas which are considered highly one-hour exposure, no significant increase in tumors was observed. Rats exposed to identical concentrations of VCM failed to elicit a tumorigenic response.

Adenoma↗
PubMed1979

Biocompatibility evaluation of casting alloys in hamsters.

A number of base metal and low gold-content alloys were evaluated in hamster cheek pouches for biocompatibility. No adverse weight changes and no abnormal behavioral patterns were noted in any of the test groups over the 14-day period of the study. Gross examination of the cheek pouches containing the alloys was no different from that of the controls. None of the alloys tested showed significant adverse histopathologic reactions. The recorded changes in incidences and degree of response were essentially no different from those of the negative control material.

Animals↗
PubMed1975

Human tissue reaction to sutures.

Tissue reaction to sutures was studied in 666 specimens obtained from patients from one day to 23 years after operation. Reaction to catgut depends on the stage of absorption and is mainly histocytic in type. Nonabsorbable sutures are encapsulated by a rim of connective tissue, while near the suture histocytes, giant cells and lymphocytes are found. This is most marked with silk and cotton, less so with Dacron, and least with nylon and wire. Tissue infiltration into the suture interstics is variable. The reactions resemble the findings in experimental animals.

Absorption↗