Oral eosinophilic granuloma in two dogs.
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Animals↗
Biomedical subjects
K M Walsh
Publications and source records attributed to K M Walsh.
Outpatient use of intermediate- and short-acting semisynthetic human insulins.
To determine if semisynthetic human insulins are useful in the outpatient management of insulin-dependent diabetes, the conditions of eight patients were evaluated for three months using short- and intermediate-acting insulins. No complications of either insulin preparation were observed. Hemoglobin A1c levels were decreased from 8.4% to 6.9% during human insulin use, and, in addition, normal hemoglobin A1c levels were maintained in patients using portable insulin infusion pumps. These results were achieved because of the health care provision team and were not directly the result of human insulin. Semisynthetic human insulins were also associated with lower levels of circulating insulin antibody. These data indicate that both short- and intermediate-acting semisynthetic human insulins are effective in stringent diabetes metabolic control, provided adequate health care provision is available.
Adult↗
Immunotoxicity of the anticancer drug CI-994 in rats: effects on lymphoid tissue.
CI-994 (acetyldinaline) is an investigative oral anticancer drug currently in clinical trials. To characterize the effects of CI-994 on lymphoid tissue, male rats were administered single oral doses at 0 (vehicle control), 10, 23, and 45 mg/kg and killed up to 7 days after dosing for evaluation of white blood cell differentials, bone marrow differentials, lymphoid tissue weights, and selected histopathology of lymphoid tissue. Statistically significant dose-related reductions in blood lymphocytes (CD-3+, CD-4+, CD-8+, CD-20+), monocytes, neutrophils, and bone marrow lymphoid cells were observed in all drug-treated groups on days 1 and/or 3. Statistically significant reductions in bone marrow myeloid cells were also observed on days 1 and 3 at 23 and 45 mg/kg. Complete or partial reversal of most parameters was evident on day 7. Spleen and/or thymus weights were significantly decreased in the groups administered 23 and 45 mg/kg on days 1, 3, and/or 7. Minor reductions in lymphoid organ weights were noted at 10 mg/kg. Minimal to moderate lymphoid depletion of the spleen and thymus was noted on day 3 in animals dosed at 23 mg/kg. In vitro, CI-994 inhibited mitogen-stimulated blood lymphocyte proliferation with a 50% inhibitory concentration (IC50) value of 3 microM. The results demonstrate that CI-994 can effect lymphoid tissue in rats within 1 day of a single oral dose, that effects are generally reversible within 7 days, and that inhibition of lymphocyte proliferation is a sensitive indicator of CI-994 immunotoxicity in vitro.
Animals↗
Effects of nonnutritive sucking on behavioral organization and feeding performance in preterm infants.
The purpose of this study was to examine the effects of nonnutritive sucking (NNS) on behavioral organization and feeding performance in preterm infants. Thirteen preterm infants were observed at four bottle-feedings, two of which involved treatment with prefeeding NNS. NNS had a positive effect on oxygen saturation and behavior state, as well as on the initiation and duration of the first nutritive suck burst.
Bottle Feeding↗
Subchronic toxicity of atorvastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor, in beagle dogs.
The toxicity of atorvastatin (AT), an inhibitor of hydroxymethylglutaryl-coenzyme A reductase (HMG), was evaluated in beagle dogs. In 4 studies [2-wk rising dose (daily increasing doses for 1 wk; maintenance for 1 wk), 12-wk rising dose (daily dosing with weekly increases in dose), 2-wk toxicity (daily dosing for 2 wk; 3 dose levels), 13-wk toxicity (daily dosing for 13 wk; 3 dose levels)], dogs received up to 400 mg/kg orally. Doses of 180 mg/kg induced moribundity, necessitating euthanasia. Weight losses up to 26% were seen at doses > or = 150 mg/kg. Decreases in cholesterol levels were dose-related. Alanine and/or aspartate aminotransferase were increased at doses > or = 80 mg/kg; alkaline phosphatase was increased at doses > or = 150 mg/kg. Histopathologic findings were seen at > or = 150 mg/kg and included hepatocellular eosinophilia related to increased smooth endoplasmic reticulum and cholangiohepatitis and cholecystitis at 150 mg/kg in the 2-wk toxicity study; hepatocellular degeneration, centrilobular bridging, cholecystitis, hemorrhage in gallbladder and brain, demyelination of optic nerve, and skeletal muscle necrosis at > or = 280 mg/kg in the 12-wk rising dose study; and erosion and hemorrhage in large intestine, hepatocellular degeneration and necrosis, and inflammation and necrosis of gallbladder epithelium at 320 mg/kg in the 2-wk rising dose study. Doses up to 80 mg/kg for 13 wk did not induce histopathologic lesions in examined organs. AT effectively lowered serum cholesterol in normal lipidemic dogs. Toxicity at AT in dogs was similar to that with other inhibitors of HMG except that lenticular changes were not seen, significant hepatic, testicular, or neurological toxicity was associated only with high doses at AT, and skeletal muscle changes similar to those described in rats and rabbits were identified.
Animals↗
Nasal toxicity of CI-959, a novel anti-inflammatory drug, in Wistar rats and Beagle dogs.
CI-959, 5-methoxy-3-(1-methylethoxy)-N-1H-tetrazol-5-yl-benzo[b]thio phene-2-carboxamide, an anti-inflammatory agent, was considered for development as a treatment for rhinitis. Two-week topical nasal studies in Wistar rats and Beagle dogs were performed to assess nasal toxicity of CI-959. Rats were given daily doses in the right nostril of 0.05 ml of solutions of varying concentrations (0.5, 2, 10, 20, 30, 60, and 90 mg/ml; doses of 0.08, 0.3, 1.6, 3.2, 4.8, 9.6, and 14.6 mg/kg) of CI-959. Beagle dogs were given daily doses in the right nostril of 0.5 ml of 10, 20, 30, 60, and 90 mg/ml solutions (doses of 0.5, 0.8, 1.2, 2.8, and 3.7 mg/kg) of CI-959. Rats given > or = 60 mg/ml either lost weight or had decreased weight gain. Salivation at dosing was seen in both species. Four sections of nasal cavity were examined from each animal. In rats, 0.5 mg/ml was the "no effect" dose; minimal changes were seen at 2 mg/ ml, and significant changes were dose related in severity at > or = 10 mg/ml in all 4 nasal levels. Degeneration and necrosis of respiratory and olfactory epithelia were minimal to moderate in severity. Adhesions and fibro-osseous proliferation of ethmoturbinates, epithelial hyperplasia, squamous metaplasia, and exudate were also seen. In dogs, 10 mg/ml was the no effect dose; respiratory epithelium was affected at > or =20 mg/ml. Respiratory epithelial degeneration was minimal to mild, with loss of ciliated and goblet cells and thinning of mucosa. Distribution of degeneration increased with increased concentrations. In both species, in accordance with the suggested action of CI-959, infiltration with neutrophils was not significant. CI-959 was locally toxic to nasal cavity respiratory and olfactory epithelia in rats and respiratory epithelium in dogs.
Administration, Topical↗
Hepatic effects in beagle dogs administered atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, for 2 years.
The chronic toxicity of atorvastatin (AT), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was evaluated in beagle dogs. Dogs were treated with 0, 10, 40, or 120 mg/kg of AT daily. Treatment lengths were 52 wk, 52 wk followed by 12 wk without drug, or 104 wk. Decreases in cholesterol levels were dose related and stable throughout the treatment period. Increases in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were transient and dose related in severity at > or = 40 mg/kg. Two dogs administered 120 mg/kg of AT daily were sacrificed moribund during the first 9 wk of treatment. Hepatic lesions were reversible with or without continued treatment and dose related in severity and distribution. Hepatic microgranulomas and hepatocellular degeneration were seen at the 120-mg/kg dose in dogs sacrificed before 53 wk. Before 53 wk, hepatocellular lipofuscin deposits were increased in dogs given > or = 40 mg/kg of AT daily but were similar to controls after 12 wk without drug and after 104 wk of continuous treatment. Bile stasis occurred in dogs given > or = 40 mg/kg of AT daily at all time points but was less severe after reversal and at week 104 compared with week 52.
Alanine Transaminase↗
Comparison of the biologic activity of porcine and semisynthetic human insulins using the glucose-controlled insulin infusion system in insulin-dependent diabetes.
Semisynthetic human insulin is prepared from porcine pancreas by chemical methods involving the substitution of porcine B-30 alanine with threonine. To compare the effectiveness of porcine and semisynthetic human insulins, eight insulin-dependent diabetic patients were evaluated during two separate periods using a glucose-controlled insulin infusion system. During each 36-h period, patients received either porcine or semisynthetic human insulin. Patients ingested mixed meals. The mean daily insulin requirements for porcine and semisynthetic human insulins were 84 +/- 9 U and 85 +/- 6 U (+/- SEM), respectively (P = NS). Mean blood glucose values were similar at 95 +/- 1 mg/dl for porcine and 101 +/- 3 mg/dl with semisynthetic human insulin (P = NS). Prior metabolic control or insulin antibody levels did not correlate with intravenous insulin requirements. These studies indicate that semisynthetic human insulin is as effective as porcine insulin in maintaining near-normal blood glucose control in short-term intravenous studies using artificial pancreas techniques in insulin-dependent diabetes.
Adult↗
Comparison of porcine insulin and human insulin (Novo) using the glucose-controlled insulin infusion system, glucose-insulin dose-response curves, and the outpatient effectiveness of human insulin (Novo) in insulin-dependent diabetes.
The usefulness of human insulin (Novo) in the treatment of diabetes was studied in eight insulin-dependent diabetic patients. Evaluation was carried out through three methods: (1) glucose-controlled insulin infusion system on two separate days during the patients' ingestion of mixed meals; (2) euglycemic clamp method; and (3) evaluation of patients for 3 mo using short- and intermediate-acting insulins. Employing the glucose-controlled insulin infusion system resulted in mean daily insulin requirements of 84 +/- 9 U and 85 +/- 6 U SEM for porcine and human insulin, respectively (P = NS). Plasma glucose levels attained during the euglycemic clamp were 96 +/- 3 mg/dl. At each insulin infusion rate, the steady-state glucose infusion rates for porcine insulin were 1.12 +/- 0.22, 1.90 +/- 0.58, 4.28 +/- 0.61, and 9.37 +/- 0.66 mg/kg/min compared with 1.27 +/- 0.42, 2.38 +/- 0.20, 4.25 +/- 0.43, and 8.87 +/- 0.67 mg/kg/min for human insulin. No complications of either insulin preparation were observed in the 3-mo patient evaluation. Human insulin was associated with lower levels of circulating insulin antibody (P less than 0.03). In addition, hemoglobin A1c levels decreased from 8.4 to 6.9% (P less than 0.035), and normal hemoglobin A1c levels were maintained in patients using portable insulin infusion pumps.
Adult↗