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Biomedical subjects

R H Garman

Publications and source records attributed to R H Garman.

At least 37 records · Page 2Linked to original sources

Primary pulmonary neoplasm in a horse.

A 16-year-old Thoroughbred gelding was evaluated for respiratory disease and found to have a primary lung tumor on postmortem examination. A tentative antemortem diagnosis was made on the basis of results of radiography and cytologic examination of a needle aspirate guided by ultrasonography. A histologic diagnosis of bronchioalveolar adenocarcinoma was made. Thoracic neoplasia is rare in horses. The most frequently reported primary pulmonary tumor is the granular cell tumor.

Adenocarcinoma, Bronchiolo-Alveolar↗

Alfentanil-induced hypermetabolism, seizure, and histopathology in rat brain.

We evaluated the effect of alfentanil on hippocampal glucose utilization and histopathology associated with alfentanil-induced seizures. Three separate experiments were performed. First, anesthetized, paralyzed Long-Evans rats (n = 15; 5 rats per group) were mechanically ventilated and randomly assigned to three groups: (a) control, 70% N2O and 30% O2 continued for 1 h; (b) low-dose alfentanil (150 micrograms/kg i.v. bolus), followed by infusion at 15 micrograms.kg-1 x min-1 for 1 h without N2O; or (c) high-dose alfentanil (1000 micrograms/kg i.v. bolus), followed by infusion at 100 micrograms.kg-1 x min-1 for 1 h without N2O. After 1 h, [6-14C]glucose was injected intravenously for autoradiography. With high-dose alfentanil, there was increased glucose utilization in the ventral hippocampus and the lateral septal nucleus. In the second experiment, anesthetized, paralyzed Sprague-Dawley rats (n = 12; 4 rats per group) were mechanically ventilated, underwent insertion of hippocampal depth electrodes, and were randomly assigned to three groups: (a) control, 70% N2O and 30% O2; (b) low-dose alfentanil (150 micrograms/kg i.v. bolus), with 70% N2O and 30% O2; or (c) high-dose alfentanil (1000 micrograms/kg i.v. bolus), with 70% N2O and 30% O2. An epileptiform pattern was observed on hippocampal and subdermal electroencephalographic recordings in both alfentanil groups. In the third experiment, anesthetized, paralyzed Sprague-Dawley rats (n = 20) were mechanically ventilated and assigned to two groups: (a) control, 70% N2O and 30% O2 (n = 5) or 100% O2 (n = 5) continued for 1 h; or (b) alfentanil (2000 micrograms/kg i.v. bolus), followed by infusion at 33.3 micrograms.kg-1 x min-1 for 1 h with 100% O2. After tracheal extubation, the rats recovered overnight. Light-microscopic evaluation revealed hippocampal or amygdaloid damage in 6 of the 10 alfentanil-treated rats. High doses of alfentanil administered to rats can produce limbic system seizure activity with hypermetabolism associated with neuropathologic lesions.

Alfentanil↗

Artifacts in routinely immersion fixed nervous tissue.

In order to demonstrate the types of artifacts commonly seen in inadequately fixed central nervous system (CNS) tissues, rat brains were fixed by either perfusion or immersion in 10% neutral buffered formalin. Perfused brains were either removed immediately or left in situ for 1 hr prior to removal. Some of the brains destined for immersion fixation were first allowed to sit for either one-half or 1 hr in either room air or in an isotonic saline solution. Other brains were subjected to various handling procedures immediately after removal from the cranial vault in order to simulate the types of trauma which commonly occur during routine removal/dissection. Commonly observed artifacts included the presence of basophilic (dark) neurons, retraction spaces around neurons, vessels, and glial cells, displacement of the neuropil, and neuropil vacuolar change. The results of the fixation and handling procedures utilized in the collection of these brains substantiate the well documented fact that the least degree of artifact will be seen in brains fixed by perfusion and left in situ for a reasonable period of time (several hours) prior to removal.

Animals↗

Biochemical and morphological studies on the percutaneous uptake of [14C] ethylenediamine in the rat.

Male Wistar rats were exposed to aqueous [14C]ethylenediamine (EDA) solutions (10, 25, or 50%) percutaneously over a 7 x 7 cm area on the back with occlusion for 24 h. For each rat dosed, three types of studies were conducted: (1) plasma kinetics, (2) material balance, and (3) histological evaluation, including autoradiography of the skin sample from the dosing area. Adequate kinetic measurements were obtained only from animals treated with 25 and 50% EDA, but not from the 10% treatment group, due to analytical limitations. The uptake of [14C]EDA percutaneously by the rat was relatively slow in comparison with uptake following peroral or endotracheal administration. The absorption of EDA by the animals was estimated to be greater than 61, 55, and 12%, respectively, for the 50, 25, and 10% treatment groups. A large portion (11-32%) of the dose was left on/in the dosing area. Urinary excretion was the predominant route for the disposition of EDA. The recovery of the administered dose was low (70-83%), possibly due to volatilization of EDA from the skin during dosing and holding. Histologic examination of skin sections (dosing areas) revealed a normal, intact epidermis in rats dosed with 10% EDA, but full-thickness epidermal necrosis in rats dosed with 25% or 50% EDA solutions. The damage of the epidermis apparently enhanced the penetration of EDA. Autoradiographic preparations revealed a concentration of the [14C]EDA radiolabel over the keratin layer and hair shafts.

Administration, Topical↗

Chronic toxicity and oncogenicity studies of ethylene glycol in rats and mice.

These studies were performed to assess the chronic toxicity and oncogenicity of ethylene glycol (EG) in rats and mice. Groups of 130 Fischer 344 rats and 80 CD-1 mice per sex were fed diets yielding approximate dosages of 1.0, 0.2, or 0.04 g/kg/day of EG. Two separate control groups in each study received no EG. Mortality rate was increased in high-dose male rats all of which died by 475 days. The following effects were also observed in high dose male rats: reduced body weight gain, increased water intake, increased blood urea nitrogen and creatinine, reduced erythrocyte count, reduced hematocrit and hemoglobin, increased neutrophil count, increased urine volume, reduced specific gravity and pH. Urinary calcium oxalate crystals and increased kidney weight were seen in all high-dose rats. Uric acid crystals were seen in the urine of high-dose female rats at 18 and 24 months. Histopathologic changes in high-dose male rats included tubular cell hyperplasia, tubular dilation, peritubular nephritis, parathyroid hyperplasia, and generalized soft tissue mineralization. Fatty change of the liver was seen in high- and intermediate-dose female rats. No clinical signs, or gross or microscopic evidence of toxicity was seen in mice at the dosages used. Water intake and clinical pathologic parameters were not measured in the mouse study. In these studies there was no evidence of an oncogenic effect of EG in rodents.

Animals↗

2,4-Pentanedione: 9-day and 14-week vapor inhalation studies in Fischer-344 rats.

Fischer-344 rats, in groups of 10 males and 10 females, were exposed for 9 days (6 hr/day) to 2,4-pentanedione (2,4-PD) vapor at mean concentrations of 805, 418, 197, and 0 (control) ppm. No deaths occurred, and the only adverse signs were of sensory irritation (partial closure of eyelids, periocular and perioral wetness) at 805 ppm. Also at 805 ppm were decreased body and organ weights, lymphocytosis, and moderate inflammation of the nasal mucosa. At 418 ppm there was a decrease in body weight gain and mild inflammation of the nasal mucosa. Apart from minimal nasal mucosal inflammation, there were no effects at 197 ppm. In the subchronic (14-week) study, rats were exposed (6 hr/day; 5 days/week) to 650, 307, 101, and 0 (control) ppm of 2,4-PD vapor, using groups containing 20 males and 20 females, with half being sacrificed at the end of the exposure period and the remainder kept for a 4-week postexposure recovery period. An additional 10 males were added to the 650 and 0 ppm groups for glutaraldehyde perfusion and subsequent electron microscopic examination of sciatic nerves. At 650 ppm, all females and 10 of 30 males died between the second and sixth weeks of exposure. These animals had acute degenerative changes in the deep cerebellar nuclei, vestibular nuclei and corpora striata, and acute lymphoid degeneration in the thymus. Seven of 15 male survivors of the 650 ppm group (combined 14-week and recovery sacrifices) had gliosis and malacia in the same brain regions, minimal squamous metaplasia in the nasal mucosa, decreased body and organ weights, lymphocytosis, and minor alterations in serum and urine chemistries. No ultrastructural evidence of peripheral neuropathy was observed. Except for central neuropathy, many of the adverse effects at 650 ppm were less marked in the 4-week recovery animals. No deaths occurred at 307 ppm, but females had slightly decreased body weight gains, and in both sexes there were minor alterations in hematology, serum chemistry, and urinalysis parameters, which were not present in the 4-week recovery animals. Rats exposed to 101 ppm showed no differences from the control rats. Subchronic exposure to 650 ppm of 2,4-PD vapor causes serious adverse biological effects. Under these study conditions, the minimum-effects concentration was 307 ppm, and the no-adverse effects concentration was 101 ppm.

Administration, Inhalation↗

Frequency, size and location of brain tumours in F-344 rats chronically exposed to ethylene oxide.

Increased frequencies of primary brain tumours were seen in male and female F-344 rats exposed to 100 or 33 ppm ethylene oxide (EO) vapour (for 6 hr daily on 5 days/wk for up to 2 yr) but no such increase was seen in rats similarly exposed to 10 ppm EO. The tumours that were seen (glial-cell tumours, granular-cell tumours and malignant reticuloses) were similar in appearance to those that develop spontaneously in F-344 rats, but the tumours associated with EO exposure at levels of 100 or 33 ppm were larger, and in at least six cases were thought to be the primary cause of death. Only two of the 23 tumours seen microscopically were detected by gross examination at necropsy, and brain weights were of minimal value in predicting the presence of tumours. Only three animals demonstrated abnormal neurological signs. These findings point to the need for thorough microscopic examination of the brains of rodents in chronic studies.

Age Factors↗

Brain tumors in F344 rats associated with chronic inhalation exposure to ethylene oxide.

Groups of F344 rats of each sex were exposed to either ethylene oxide (ETO) vapor (concentrations of 100, 33 or 10 ppm) or to room air for 6 hours daily, 5 days per week, for up to 2 years. Three representative sections of the brain from each rat were evaluated. Twenty-three primary brain tumors were found, two of which were in control animals. Increased numbers of brain tumors were seen in 100 ppm and 33 ppm ETO exposed male and female rats. Significant trend analyses were found for both males and females, indicating that, under the conditions of this study, ETO exposure above 10 ppm was related to the development of these brain tumors.

Air Pollutants↗

Two-generation reproduction study of ethylenediamine in Fischer 344 rats.

Ethylenediamine dihydrochloride (EDA X 2 HCl) was incorporated in the diet of Fischer 344 rats at dosage goals of 0.50, 0.15, 0.05, or 0 g/kg/day in a two-generation reproduction study. The parent generation (F0) and the F1 generation were each bred once. Parameters examined included indices of fertility, gestation of dams, gestation survival, 0- to 4-, 4- to 14- and 4- to 21-day survival of pups, number of pups born alive, and number of pups weaned per litter. Furthermore, observations were made on mortality, diet consumption, and body weight of the adult rats in F0 and F1 generation. Randomly selected F1 weanlings and adults and F2 weanlings were sacrificed and organ weights were obtained; in addition, gross and histologic examinations were conducted on these rats. No reproductive toxicity was observed in this study. Some effects were observed in both sexes for the F0 and F1 parent rats. These effects were mainly associated with the high dosage level and included reduction of body weight gain and changes in liver (decrease) and kidney (increase) weights in the adult rats. The only microscopic lesion observed was hepatocellular pleomorphism in the high level F1 adult males and females; a greater prevalence and severity of this lesion was seen in the female rats.

Animal Feed↗

Subchronic and reproductive toxicology studies on acrylic acid in the drinking water of the rat.

In the subchronic study acrylic acid was incorporated in the drinking water of Fischer 344 rats (15 per group) for three months at dosage levels of 0.75, 0.25, 0.083 or 0 g/kg/day. No deaths occurred during the study but several treatment-related effects were observed. At 0.75 g/kg/day dosage level, body weight gain was reduced as were food and water consumption. Changes in organ weights and clinical chemistry parameters were observed along with increases in urine specific gravity and protein concentration. Similar, though less profound, changes occurred at 0.25 g/kg/day. At 0.083 g/kg/day, the only effect was a reduction of water consumption by male rats. There were no significant treatment-related histopathologic changes. Many of the effects observed may have been the result of decreased water and food consumption rather than specific toxic effects of acrylic acid. In the reproduction study, the same dosages of acrylic acid were given to groups of 10 males and 20 females for 90 days after which the animals were mated. Treatment was continued throughout gestation and lactation. Treatment-related effects included decreased body weight gain, and reduced food and water consumption in F0 rats at the 2 highest dosage levels. Organ weight changes occurred in both F0 and F1 animals and reduced body weight gain was seen in the F1 pups at the highest level. No statistically significant changes in reproductive indices were observed, perhaps because of an atypical control group.

Acrylates↗

Spontaneous cardiac tumors in eight rats.

Spontaneous cardiac neoplasms were diagnosed in one Sprague-Dawley and seven Fischer 344 rats ranging in age from eight months to two years. All eight neoplasms were diagnosed as neurilemmomas. One neoplasm was composed of dense Antoni type A tissue with Verocay body formation, while seven others were composed principally of loose Antoni type B tissue. No specific site predilection was found.

Animals↗

Neurotoxicity of methylmercury in the pigeon.

Pigeons repeatedly exposed to sublethal doses of methylmercury (5-10 mg Hg/kg/wk, po, for 34-77 days) exhibited marked behavioral changes that were accompanied by only minor evidence of neuropathologic changes at the light microscopic level. Accuracy and rate of pecking for grain declined while food intake remained unchanged. Methylmercury produced permanent changes in posture and in motor coordination. The regional distribution of methylmercury within the nervous system was poorly correlated with the distribution of pathologic changes. Overt behavioral signs appeared after the brain accumulated more than about 12 to 16 ppm Hg. Data with pigeons support earlier evidence that the dose-response function for methylmercury is modulated by dose rate and duration of exposure, since the pattern of blood and tissue distribution of Hg is established in advance of the appearance of signs. The pigeon is more sensitive to methylmercury than are mice and rats, but less sensitive than primates.

Animals↗

Toxic epidermal necrolysis in a monkey (Macaca fascicularis).

An adult male Macaca fascicularis monkey developed toxic epidermal necrolysis after ingestion of methylmercury. The clinical picture was characterized by the development of large cutaneous bullae with subsequent full-thickness epidermal exfoliation. Areas of sparse pelage were most affected, with the most severe exfoliation occurring on the palms, soles, face and ears. Erosions also developed within the oral mucosa and conjunctivae.

Animals↗

Effects of fluoroacetate on the testis of the rat.

Rats recieving 20, 6.6 or 2.2 p.p.m. sodium fluoroacetate in the drinking water were killed daily during the 7 days of treatment and at more widely spaced intervals in the succeeding 21 days. Testicular weight and ATP concentrations decreased in rats receiving 20 or 6 p.p.m. fluoroacetate, while citrate concentrations were elevated and morphological damage was seen in the testes of all the treated rats. Initial cellular changes common to the three treatment groups included altered appearance and decreased numbers of spermatids, and formation of spermatid and spermatocyte giant cells. At the two higher concentrations damage progressed to marked seminiferous tubule atrophy. Regeneration of the seminiferous tubules was complete by 7 days after treatment, in the rats given 2 p.p.m. but regeneration was not complete by Day 21 after treatment in those receiving the higher doses. Spermatogenesis was abnormal in some instances during the regneration period in these groups. The findings are consistent with impaired energy production via blockage of the Krebs cycle, and subsequent impairment of carbohydrate metabolism through the Embden-Meyerhof pathway.

Adenosine Triphosphate↗