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Biomedical subjects

D G Hoffman

Publications and source records attributed to D G Hoffman.

12 recordsLinked to original sources

Studies to elucidate the mechanism of fenarimol-induced infertility in male rats.

Fenarimol (alpha-(2-chlorophenyl)-alpha-(4-chlorophenyl)-5- pyrimidinemethanol a pyrimidine carbinol fungicide, caused a dose-related decrease in male fertility in Wistar rats. The effect was particularly evident in the anatomically normal progeny of dams treated with fenarimol throughout gestation and lactation. Based on the observation that the infertility was associated with the absence of vaginal sperm at the time of mating, the effect appeared to be the result of an absence of male sexual behavior. Fenarimol does not readily cross the placenta but does concentrate in milk, reaching three- to fivefold higher concentrations than those observed in the maternal plasma. These results suggest that fenarimol might be acting to block the perinatal development of male patterns of sexual behavior which involves the action of gonadal steroids within the central nervous system (CNS). To test this hypothesis, [14C]fenarimol was administered to dams and the radioactivity measured in the brains of the neonates. Radioactivity in the hypothalamus was three- to fourfold higher and the half-life four times longer than that observed in the remainder of the brain. Since the hypothalamus is believed to play a key role in the development and expression of male sexual behavior, it appears likely that fenarimol is acting centrally to decrease male sexual behavior, thereby decreasing male fertility.

Administration, Oral

Transcervical myotomy for wide-gap esophageal atresia.

A primary end-to-end anastomosis of the esophagus can be accomplished in the wide-gap esophageal atresia by obtaining extra esophageal length through circular myotomy of the proximal esophageal pouch. However, a very short proximal esophageal pouch may not be accessible through the standard thoracic incision, precluding this procedure. An infant is reported in whom the inaccessible proximal pouch was exteriorized into the neck through a concomitant cervical incision, allowing three circular myotomies to be performed with ease. The proximal esophagus was then reintroduced into the chest cavity and a primary esophagoesophagostomy performed without difficulty.

Esophageal Atresia

An evaluation of the toxicity of cefaclor in laboratory animals.

The toxicity of cefaclor, a new orally-administered cephalosporin, was evaluated in laboratory animals given single or multiple doses of the antibiotic. The acute toxicity data for cefaclor in mice, rats, dogs and monkeys were comparable to that previously reported for cephalexin. Rats were maintained on dietary mixtures of cefaclor which provided average daily doses of approximately 230 to 950 mg/kg for 28 days in subacute toxicity tests, and 160 to 675 mg/kg for 1 year in chronic toxicity tests. Treatment-related effects in the above studies were limited to soft stool excretion and caecal dilatation in the subacute test. Effects in dogs given daily oral doses of 50 to 200 mg/kg for 30 days were limited to a transient moderate fall in haemoglobin concentration in the two males at the highest dose. Soft stool excretion and occasional episodes of emesis were observed in dogs given cefaclor for 1 year at oral doses of 100 to 400 mg/kg/day. A reversible thrombocytopenia occurred in one animal at the highest dose. Analysis of various tissue fluids taken 2 hours after the last dose revealed that the concentration of cefaclor in the synovial fluid was approximatley one-half of that in serum. The results of these studies indicate that cefaclor has a low toxic potential in the species tested.

Animals

Metabolism of a new herbicide, tebuthiuron (1-[5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]- 1,3-dimethylurea), in mouse, rat, rabbit, dog, duck, and fish.

Orally dosed tebuthiuron was readily absorbed in mice, rats, rabbits, dogs, and ducks. The compound was extensively metabolized and the metabolites were rapidly excreted in the urine of mice, rats, rabbits, and dogs and in the mixture of urine and feces in ducks. The major metabolites of tebuthiuron were formed by N-demthylation of the substituted urea side chain in each species examined, including fish. Oxidation of the dimethylethyl group occurred in mice, rats, dogs, rabbits, and ducks. The N-demethylation reaction at the 3-position of the urea proceded through an N-hydroxymethyl intermediate. No accumulation of tebuthiuron or its metabolites was observed in the animals, a finding consistent with the low order of toxicity observed in other studies.

Animals