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Biomedical subjects

D W Coombs

Publications and source records attributed to D W Coombs.

84 records · Page 5Linked to original sources
PubMed1979

Comparative effects of repeated and prolonged inhalation exposure of beagle dogs and Cynomolgus monkeys to anaesthetic and subanaesthetic concentrations of enflurane and halothane.

Male and female Beagle dogs and Cynomolgus monkeys were exposed to anaesthetic (1.5 MAC) and subanaesthetic (1/100 MAC) levels of enflurane and halothane for 3 hours on alternate days for 4 weeks. One-half of the animals were killed following the last exposure and the remainder after 4 weeks of recovery. The animals' condition was assessed during anaesthetic periods by measuring respiration, ECG, blood pressure, temperature and EEG. Haematology, urinalysis and clinical chemistry parameters were evaluated. Gross and microscopic pathological examinations were conducted at the end of the exposure and recovery periods. Two female monkeys in the mid- and high-dose halothane groups died during the study. No deaths were observed in the enflurane group. No quantitative differences were observed in respiration rate, heart rate, blood pressure and EEG activity of animals anaesthetized with enflurane or halothane. Muscle twitches were observed in some mid- and high-dose dogs inhaling enflurane, but not in monkeys. A number of liver function tests became abnormal in mid- and high-dose halothane-treated dogs and high-dose halothane-treated monkeys. This was not observed with enflurane. Histopathologic alterations were confined to the liver of animals exposed to halothane. In dogs, the lesions were characterized by centrilobular hepatocyte degeneration and/or necrosis, fibroblastic proliferation, hepatocyte enlargement, fat deposition and glycogen depletion; and in mid- and high-dose monkeys by moderate to marked hepatocyte vacuolation and fat deposition. Except for one high-dose dog, these lesions were not seen in animals killed after 4 weeks of recovery. No histopathologic alterations were observed with enflurane.

Alanine Transaminase↗
PubMedDate not supplied

Chronic toxicity/oncogenicity study of styrene in CD-1 mice by inhalation exposure for 104 weeks.

Groups of 70 male and 70 female Charles River CD-1 mice were exposed whole body to styrene vapor at 0, 20, 40, 80 or 160 ppm 6 h per day 5 days per week for 98 weeks (females) or 104 weeks (males). The mice were observed daily; body weights, food and water consumption were measured periodically, a battery of hematological and clinical pathology examinations were conducted at weeks 13, 26, 52, 78 and 98 (females)/104 (males). Ten mice of each gender per group were pre-selected for necropsy after 52 and 78 weeks of exposure and the survivors of the remaining 50 of each gender per group were necropsied after 98 or 104 weeks. An extensive set of organs from the control and high-exposure mice were examined histopathologically, whereas target organs, gross lesions and all masses were examined in all other groups. Styrene had no effect on survival in males. Two high-dose females died (acute liver toxicity) during the first 2 weeks; the remaining exposed females had a slightly higher survival than control mice. Levels of styrene and styrene oxide (SO) in the blood at the end of a 6 h exposure during week 74 were proportional to exposure concentration, except that at 20 ppm the SO level was below the limit of detection. There were no changes of toxicological significance in hematology, clinical chemistry, urinalysis or organ weights. Mice exposed to 80 or 160 ppm gained slightly less weight than the controls. Styrene-related non-neoplastic histopathological changes were found only in the nasal passages and lungs. In the nasal passages of males and females at all exposure concentrations, the changes included respiratory metaplasia of the olfactory epithelium with changes in the underlying Bowman's gland; the severity increased with styrene concentration and duration of exposure. Loss of olfactory nerve fibers was seen in mice exposed to 40, 80 or 160 ppm. In the lungs, there was decreased eosinophilia of Clara cells in the terminal bronchioles and bronchiolar epithelial hyperplasia extending into alveolar ducts. Increased tumor incidence occurred only in the lung. The incidence of bronchioloalveolar adenomas was significantly increased in males exposed to 40, 80 or 160 ppm and in females exposed to 20, 40 and 160 ppm. The increase was seen only after 24 months. In females exposed to 160 ppm, the incidence of bronchiolo-alveolar carcinomas after 24 months was significantly greater than in the controls. No difference in lung tumors between control and styrene-exposed mice was seen in the intensity or degree of immunostaining, the location of tumors relative to bronchioles or histological type (papillary, solid or mixed). It appears that styrene induces an increase in the number of lung tumors seen spontaneously in CD-1 mice.

Administration, Inhalation↗
PubMedDate not supplied

Conceptual and methodologic problems in the evaluation of a new burn treatment modality.

This article describes and analyzes major conceptual and methodologic problems that occurred during the implementation and evaluation of a new home-based burn treatment modality. Problems described include those of conceptualization, measurement, patient sampling, and follow-up, data collection, and analysis. The origins of each specific problem are discussed along with their effects on the implementation of the project and project outcomes. Solutions for each set of problems are suggested.

Ambulatory Care↗
PubMedDate not supplied

Pre-anesthetic cimetidine alteration of gastric fluid volume and pH.

Gastric volume and pH were studied immediately after induction of anesthesia and endotracheal intubation in 101 elective surgical patients. Of 44 patients not given cimetidine, 82% had a gastric pH less than 2.5 with a mean pH of 1.6; 45% of these patients had a gastric aspirate pH less than 2.5 associated with a volume exceeding 25 ml. In 57 patients premedicated with intravenous cimetidine at variable intervals (15 to 60 minutes) prior to induction of anesthesia, a significant time-dependent increase was noted in gastric pH (p less than 0.001) together with a decline in gastric volume (p less than 0.001). Of the patients given intravenous cimetidine (mean 4.5 mg/kg) 45 minutes prior to induction of anesthesia, 90% had a gastric pH greater than 2.5. The increase in gastric pH after cimetidine administration would result in a reduced chemical pulmonary reaction should aspiration occur during induction of anesthesia.

Adolescent↗
PubMedDate not supplied

Toxicity of chronic spinal analgesia in a canine model: neuropathologic observations with dezocine lactate.

The chronic spinal toxicity of dezocine lactate was investigated in mongrel dogs. Dogs received chronic intrathecal infusion from implanted infusion pumps for 28-136 days. Infusion of saline via intrathecal catheters produced leptomeningeal fibrosis, sometimes with spinal cord compression. Dezocine lactate infusion, in addition to similar leptomeningeal changes, was also associated with severe parenchymal lesions in all cases. The exact cause of this toxicity cannot be specifically assigned; potential contributing factors include catheter-induced reaction, pH of the drug, lactate concentration, osmolality and the pharmacologic agent itself. Leptomeningeal reaction in control dogs limits the value of chronic intrathecal dog models for assessment of spinal drug toxicity.

Analgesics, Opioid↗
PubMedDate not supplied

Testing an implantable intraspinal drug delivery device in the ewe.

OBJECTIVE: The authors report the use of multiple implanted intraspinal port and catheter systems per test animal to study the in vivo functional characteristics and reliability of a new implantable spinal drug delivery port system. METHODS: Four ewes were each implanted with two epidural and one subarachnoid silicone elastomer catheters at the lumbar level. Each catheter was connected in series to one of three Therex filtered spinal delivery ports implanted subcutaneously in a similar grid pattern in each ewe to facilitate percutaneous identification. Saline (2 ml) was injected 3 times weekly in each port. The ease of injection and behavioral responses were recorded for 207-213 days of implantation until sacrifice/necropsy. RESULTS: All ports functioned reliably during the study. However, injection through two of the four subarachnoid catheters resulted in behavioral withdrawal responses intermittently. This behavioral pattern was much less common after epidural port injections. All four subarachnoid and four of eight epidural port and catheter systems were tested with local anesthetic just before sacrifice. Motor block was observed in three of four subarachnoid and three of four epidural port and catheter systems tested. Integrity of the other four epidural ports was tested by injection of methylene blue at sacrifice. This dye did not distribute in the epidural space in one of the latter four epidural ports (not local anesthetic tested) because of a concentric fibrotic reaction about the catheter. Similar fibrotic reactions surrounded the catheters that failed a functional test with local anesthetic. CONCLUSIONS: The implantable intraspinal port system tested functions reliably under repetitive percutaneous access. However, filtering such ports, though desirable to prevent entry of debris into the spinal canal, did not eliminate pericatheter chronic subarachnoid and epidural reaction. The number of test animals required to test 12 ports chronically was reduced by two-thirds without undue trauma to the individual test subject. Chronic percutaneous injection of an implanted subarachnoid system is feasible but may be associated with behavioral effects similar to that seen with chronic epidural systems. Fibrosis around chronic silicone catheters limited functional utility in one-fourth of the implanted test systems. Further study of the potential reactivity of chronic epidural and subarachnoid catheters is indicated.

Animals↗