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Biomedical subjects

T R Lewis

Publications and source records attributed to T R Lewis.

At least 37 records · Page 2Linked to original sources
PubMed1984

Low-dose chronic inhalation of diesel exhaust and/or coal dust by rats: effect of age and exposure on lung and liver cytochrome P-450.

Rats were exposed by inhalation to low levels of diesel exhaust and/or coal dust, seven hours/day, five days/week for 24 months. Cytochrome P-450-associated benzo[a]pyrene hydroxylase and 7-ethoxycoumarin deethylase activities were assayed in lung and liver microsomes after 3, 6, and 24 months. When data were analysed across all time intervals and adjusted for age, lower benzo[a]pyrene hydroxylase activity was observed in lung microsomes from rats exposed to diesel exhaust plus coal dust than in those exposed to coal dust alone. Data are discussed in terms of interaction between diesel exhaust and coal dust and effect of infectious agents.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1984

Toxicity evaluation of sub-chronic exposures to cyanogen in monkeys and rats.

A 6 mon (6 hr/day, 5 days/week) inhalation toxicity study was conducted with cyanogen gas using male rhesus monkeys (Macacca mulatta) and male albino rats (Charles River Strain) as experimental animals. Fifteen monkeys and 90 rats were divided into three groups of 5 monkeys and 30 rats. One group, the Controls, was not exposed to the test material; the other two groups were exposed to either 11 ppm or 25 ppm cyanogen. At the outset of exposures, there was a doubling of the rate of responding on a variable interval 2.9 min schedule of reinforcement in monkeys exposed to 25 ppm cyanogen, and increases were also seen in the monkeys receiving 11 ppm exposures; the increases were transitory as the rate returned to control levels before exposures were terminated. At the end of the 6 mon exposure, there were no effects in hematologic or clinical chemistry parameters attributable to the inhalation exposure to cyanogen. The electrocardiograms, and gross pathologic and histopathologic examinations of test animals were normal when compared with the Control animals. Total lung moisture content was significantly lower in monkeys exposed to either 11 ppm or 25 ppm cyanogen than in Control animals. Body weights were significantly lower in rats exposed to 25 ppm than in Controls. The results suggest that subchronic 25 ppm cyanogen exposures are marginally toxic, but the evidence on 11 ppm does not support a similar conclusion.

Animals↗
PubMed1983

Pulmonary hyperreactivity in cynomolgus monkeys (Macaca fascicularis) from nose-only inhalation exposure to disodium hexachloroplatinate, Na2PtCl6.

The pulmonary and dermal effects of exposure to Na2PtCl6 were investigated in cynomolgus monkeys (Macaca fascicularis) exposed by the nose-only inhalation and percutaneous routes. Separate inhalation exposures were performed in monkeys at 200 micrograms/m3 and 2 mg/m3 (4 hr/day, biweekly for 12 weeks), while another group of monkeys was percutaneously exposed biweekly by an open patch method. After a 2-week refractory period, serial Na2PtCl6 bronchoprovocation challenges and intradermal Na2PtCl6 sensitivity evaluations were performed. Na2PtCl6 bronchoprovocation in naive control monkeys yielded significant impairments in post-challenge pulmonary mechanics and ventilatory function. These results indicate a pharmacologic or irritant-mediated bronchoconstriction mechanism for acute exposure to this compound. When the post-challenge pulmonary function of animals exposed for the 12-week exposure regimen (across treatments) was compared to pulmonary deficits observed in control animals upon challenge, significantly greater pulmonary deficits were seen in animals exposed at the 200 micrograms/m3 concentration. Exposure at this concentration yielded significant changes in post-challenge average pulmonary flow resistance (RL) and forced expiratory volume in 0.5 sec corrected for vital capacity (FEV0.5/FVC) when compared to control monkey responses. Animals exposed by the percutaneous route or at 2 mg/m3 showed no significant post-challenge pulmonary deficits when compared to control animals. Intradermal Na2PtCl6 sensitivity was found not to be exposure related in the conditions of this experiment.

Aerosols↗
PubMed1982

Incidence of lobular carcinoma in bilateral breast cancer.

The histology and clinical records of 52 patients with bilateral breast cancer recorded in a community tumor registry were reviewed. Previous studies have demonstrated the propensity of lobular carcinoma to occur bilaterally. This view is supported by the large number of lobular cancers found in our patients. Thirty-six percent of the patients with bilateral disease had lobular cancer in at least one breast. Those with lobular cancer tended to be younger and more likely to have simultaneous cancers than did patients with nonlobular carcinoma. In those patients in whom the occurrence of tumors was not simultaneous, they were smaller in the second breast but had similar rates of axillary metastases. This study raises the question of how best to manage the contralateral breast in patients with breast cancer. Lobular carcinoma is one marker of the likelihood for development of disease in the second breast; but if advantage is to be gained by this finding, investigation of the opposite breast is best done early. Finally, thorough examination of patients with nonlobular carcinoma must not be ignored because they still comprise the majority of bilateral breast cancers.

Adult↗
PubMed1981

Pneumoconiosis in animals exposed to poly(vinyl chloride) dust.

Rats, guinea pigs and monkeys were exposed by inhalation (6 hr/day, 5 days/week) for up to 22 months to a 13 mg/m3 concentration of PVC dust. Autopsies on rats and guinea pigs were performed after 12 months of exposure and on monkeys after 22 months after 22 months of exposure. Lung function tests were performed on monkeys after 9, 14 and 22 months of exposure. Aggregates of alveolar macrophages containing PVC particles were found in the lungs of all animals. These aggregates were more numerous in the monkey lungs. No fibrosis or significant cellular infiltrates were present in or near these cellular aggregates. No significant effects on pulmonary function could be demonstrated in the monkeys exposed to PVC. Under the conditions of this experiment, inhaled PVC produced a benign pneumoconiosis.

Animals↗
PubMed1979

(2,6-Methano-3-benzazocin-11 beta-yl)alkanones. 1. Alkylalkanones: a new series of N-methyl derivatives with novel opiate activity profiles.

A general stereospecific synthesis of (N-methyl-2,6-methano-3-benzazocin-11 beta-yl)alkanones is described and applied to the preparation of a series of alkyl ketones wherein the alkyl group is a straight or terminally branched chain containing from one to six carbon atoms. Several compounds with methoxy groups in the aromatic ring are in the morphine range of potency; they are uniformly inactive as phenazocine antagonists. Phenolic analogues range up to 100 times as potent as morphine. Those containing five or six carbon atoms in the alkyl group exhibit phenazocine antagonist activity, in one case equivalent to naloxone. This compound (3e) is selective for phenazocine in its antagonist action.

Analgesics, Opioid↗
PubMed1979

Chronic exposure to low concentrations of halothane-nitrous oxide: lack of carcinogenic effect in the rat.

The effects of prolonged exposure to low-concentration combinations of halothane and nitrous oxide on tumor incidence, especially with regard to the reticuloendothelial system, were studied. Three groups of 50 male and 50 female Fischer 344 rats each were studied. For seven hours/day, five days/week, for 104 weeks, Group I was exposed to filtered air (control); Group II, to halothane, 1 ppm, and nitrous oxide (N2O), 50 ppm; Group III, to halothane, 10 ppm, and N2O, 500 ppm. No evidence of exposure-related effects on body weight, appearance, behavior, survival, or hematologic findings was found. Histologic evaluation of the reticuloendothelial system and of other major organs revealed neither enhancement of the spontaneous tumor rate nor any unusual neoplasm. Thus, this study did not lend support to the hypothesis that these anesthetic agents in low concentrations are responsible for the reportedly higher than average incidence of reticuloendothelial malignancies in operating room personnel.

Animals↗
PubMed1978

An electrodiagnostic study of the neurotoxicity of methyl n-amyl ketone.

The neurotoxicity of methyl n-amyl ketone was investigated in a chronic inhalation study lasting 9 months. Rats and monkeys were exposed 6 hrs/day, 5 days/week, to mean MAK levels of 0, 131, and 1025 ppm. Electrodiagnostic measures of nervous system function revealed no neurotoxic impairment at either MAK exposure. Body weights were similarly unaffected. Gross and histopathology also indicated no adverse effects of MAK. It was concluded that MAK does not possess neurotoxic properties similar to those possessed by methyl n-butyl ketone.

Action Potentials↗
PubMed1978

Acute toxicity of tetramethylbenzenes: durene, isodurene and prehnitene.

Oral LD50 (rat), primary skin irritation (rabbit), cutaneous sensitization (guinea pig) and eye irritation (rabbit) studies were conducted on the three tetramethylbenzene isomers: durene , isodurene and prehnitene. The order of oral toxicity was isodurene greater than prehnitene greater durene. Durene was not a skin irritant, while isodurene and prehnitene each produced a mild positive skin response (erythema). None of the tetramethylbenzenes were skin sensitizers or eye irritants. Durene, isodurene and prehnitene are only slightly toxic on an acute toxicologic basis and only pose an acute health hazard when injested in excessive quantities.

Animals↗
PubMed1977

Effects of methyl n-butyl ketone behavior and the nervous system.

The effects of methyl n-butyl ketone (MBK) on nervous system function and operant behavior were investigated in monkeys and rats. Mean MBK exposure levels approximated 100 and 1000 ppm and lasted up to 10 months. Both exposures were 6 hours/day 5 days/week. Results showed that the 1000 ppm exposure effected 1) reduced motor conduction velocities in ulnar and sciatic-tibial nerves, 2) decreased the amplitude of evoked muscle action potentials, 3) lengthened implicit time of visual evoked potentials, 4) impaired operant behavioral performance, and 5) reduced body weight. Reductions in nerve conduction velocities and evoked muscle action potentials were found at 100 ppm. Recovery, as measured by sciatic-tibial nerve conduction velocity, was found to occur 6 months and 2 months after termination of the 1000 ppm and 100 ppm MBK exposures, respectively.

Action Potentials↗
PubMed1975

Absorption, distribution and excretion of terephthalic acid and dimethyl terephthalate.

Data from a radiotracer study in rabbits and rats to determine the absorption, distribution, and excretion of terephthalic acid (TA) and dimethyl terephthalate (DMT) following oral, intratracheal, dermal and ocular administration indicate the following: (1) a rapid absorption and excretion of 14C-TA and 14C-DMT with no evidence of tissue accumulation in rats following single or repeated oral and intratracheal administration; (2) no evidence of skin irritation in rats after a single or repeated dermal application of 80 mg of 14C-TA or 14C-DMT and no significant skin absorption of 14C-TA; (3) recovery of approximately 11% of a single dose and 13% of five repeated cutaneous doses of 14C-DMT from the urine and feces of rats within 10 days after initial dosing; (4) no significant absorption of 14C-TA when applied to the conjunctival sac of one eye of eight rabbits; (5) excretion of approximately 33% of a single ocular dose (50 mg) of 14C-DMT in the urine and feces of rabbits within 10 days after instillation with no evidence of tissue accumulation or ocular damage. These results suggest that TA and DMT are rapidly absorbed and excreted and that no significant quantities of these compounds accumulate in the tissues following single or repeated oral, intratracheal, dermal, or ocular administration to laboratory animals.

Administration, Oral↗
PubMed1975

Repeated topical applications of 1,2,4-trichlorobenzene. Effects on rabbit ears.

In a study to evaluate its acnegenic potential, increasing concentrations of 1,2,4-trichlorobenzene were applied topically to the ventral surface of the rabbit ear three times weekly for 13 weeks. Additional groups of rabbits received similar treatment with petroleum ether (solvent controls), received no treatment (negative controls), and received four once-weekly treatments with hexachlorodiphenyloxide, a known chloracnegenic agent (positive controls). Skin response to 1,2,4-trichlorobenzene was characterized grossly by dermal irritation directly related to the concentration of test material; there were the associated histologic changes of acanthosis and hyperkeratosis; there was no primary follicular involvement characteristic of acneform dermatitis. Dermal responses to hexachlorodiphenyloxide consisted of gross follicular enlargement, with waxy excretion on pressure, and severe scaling. The affected ear appeared thickened up to three times normal size and histologic sections showed primary follicular involvement characterized by marked thickening of the sheath and marked distention of the follicles with keratin, with resultant comedone formation, typical of chloracne.

Acne Vulgaris↗
PubMed1975

Maximum expiratory flow-volume studies on monkeys exposed to bituminous coal dust.

To assess early ventilatory responses at the 2 mg/m3 bituminous coal dust standard, 23 cynomolgus monkeys were exposed by inhalation to Pennsylvania and Utah coal dust. Ten controls were utilized. Pennsylvania coal was selected from a field having a high prevalence of coal workers' pneumoconiosis while the Utah coal was selected from a low prevalence area. After 24 mo of exposure, a pattern of pulmonary impairment consistent with peripheral airway obstruction was demonstrated. Reductions were observed in the forced expiratory volume in 1 s, maximum midexpiratory flow rate, and especially maximum expiratory flow at small lung volumes. Hyperinflation (RV/TLC) was observed in both coal treatments; however, no specific lung volumes differed significantly from controls. No differences were found between the Pennsylvania and Utah treatments. Design and specifications for a new hydraulically operated plethysmograph-respirator are included.

Animals↗