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Biomedical subjects

S C Lewis

Publications and source records attributed to S C Lewis.

At least 19 recordsLinked to original sources
PubMed1995

Attitudinal survey of adverse drug reaction reporting by medical practitioners in the United Kingdom.

1. Attitudes of doctors to the Committee on Safety of Medicines' (CSM) adverse drug reaction (ADR) reporting scheme were investigated in order to assess their understanding of the purposes of the scheme and to identify reasons for failing to report suspected adverse drug reactions. 2. A postal questionnaire and letter of invitation were sent to 500 doctors who were randomly selected from the 1992 Medical Directory. A reminder letter and a second copy of the questionnaire were sent to non-responders after 4 weeks. 3. 284 (57%) responded to the questionnaire. Of these, 179 (63%) stated that they had previously reported an ADR to the CSM or a pharmaceutical manufacturer. 77% of general practitioners stated that they had reported one or more ADRs compared with 55% of hospital doctors. 4. Reasons for under-reporting included lack of time, lack of report forms and the misconception that absolute confidence in the diagnosis of an adverse reaction was important in the decision to send in a report. 5. An investigation of seven commonly proposed reasons for under-reporting showed that on the whole they did not apply. 6. Most doctors knew the types of reactions that the Committee on Safety of Medicines seeks reports for but only 38% knew the precise meaning of the Committee on Safety of Medicines' black triangle symbol. There also seemed to be confusion about some of the purposes of the adverse drug reaction reporting scheme. 7. The number of reporting doctors is much higher than has previously been estimated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adverse Drug Reaction Reporting Systems↗
PubMed1995

Subchronic feeding study of four white mineral oils in dogs and rats.

Subchronic 90-day feeding studies were conducted on four highly refined white mineral oils to determine any potential for toxicity in Long-Evans rats (20 per sex per dose level) and beagle dogs (4 per sex per dose level). Each oil was fed at dietary dose levels of 300 ppm and 1500 ppm (w/w). No treatment-related effects of toxicological importance were detected in daily observations of general health or in periodic assessments of food consumption and body weight, hematology, serum clinical chemistry, and urinalysis. Observations in dogs suggested that the white oils produced mild laxative effects. Gross and histopathologic examinations, as well as measurements of organ weights, did not reveal any macroscopic or microscopic changes which could be due to treatment. In addition, special staining by Oil Red O of liver, mesenteric lymph nodes, spleen, gastrointestinal tract, stomach, and kidneys indicated no evidence of oil or lipid deposition. A special re-examination of tissues from female and male rats, in response to more recent conflicting data from the Fischer 344 strain, found no histopathologic signs of macrophage accumulation and/or microgranuloma formation in liver, spleen, or mesenteric lymph nodes. These data indicate that repeated exposure to relatively high levels of white mineral oils in the diets does not produce significant subchronic toxicity in Long-Evans rats or beagle dogs.

Animals↗
PubMed1992

Developmental toxicity of dimethylformamide in the rat following inhalation exposure.

Dimethylformamide (DMF) is a widely used industrial solvent. DMF has been reported to be a developmental toxin when given to rodents by injection or following dermal administration. In this study, groups of pregnant rats were exposed by inhalation to either 0 (control), 30, or 300 ppm DMF from gestation day 6 through 15. In the 300 ppm rats, both maternal weight gain during gestation and fetal weights were lower than those of the controls. Fetal resorptions were not increased in this group. No significant differences among either maternal or fetal rats were seen in the 30 ppm group compared to controls. Both fetal and maternal toxicity were noted at 300 ppm and the no observed effect level under these experimental conditions was 30 ppm for both the dams and the conceptuses. DMF did not produce malformations in the rat fetus even at a level that was toxic to the dam.

Abnormalities, Drug-Induced↗
PubMed1990

Estimation of epidermal carcinogenic potency.

This report compared two statistical methods of estimating tumor latency, the Weibull distribution model and the Kaplan-Meier method. Parallelism of dose-response curves of different materials and quantitative reproducibility of dermal carcinogenesis data were also examined. The Weibull method has the advantage of producing parameter estimates, even when tumor yield is low. The Kaplan-Meier method, on the other hand, is free of distribution assumptions. Overall, since the comparisons of potency are made on the basis of parameters from the same assumed distribution on the same strain of animal, the Weibull estimates are favored. A comparison of dose-response data for benzo[a]pyrene and catalytically cracked clarified oil indicated that the slopes of the two dose-response curves were significantly different. Thus the relative carcinogenic potencies of different materials vary with dose, and potency comparisons must necessarily be dose-specific. The quantitative reproducibility of dermal carcinogenesis bioassays was also assessed. The dose-response curves from the three studies of one material had significantly different slopes. Thus the results suggested that there were sources of biological variability which could contribute to experimental error.

Animals↗
PubMed1990

A scheme for classifying carcinogens.

We present a scheme for classifying chemical carcinogens according to the weight of the evidence that each substance poses a human cancer hazard. The approach represents a logical extension of and builds upon those previously developed by the International Agency for Research on Cancer, the U.S. Environmental Protection Agency, and the so-called Tripartite Group of industrial scientists. It takes into account new scientific knowledge about chemical carcinogenesis and animal models. Eight categories are presented: known human carcinogen (Category 1), carcinogenic activity in animals, probable human carcinogen (Category 2), possible human carcinogen (Category 3), equivocal evidence for carcinogenic activity (Category 4), evidence inadequate for classification (Category 5), carcinogenic activity in animals; probably not a human cancer hazard (Category 6), carcinogenic activity in animals; considered not a human cancer hazard (Category 7), evidence of noncarcinogenicity (Category 8). Evidence useful for categorization includes human studies, animal bioassays, corroborative evidence from bioassays, and mechanistic studies relevant to determining the predictivity of animal responses for human hazard. Weighing this evidence to derive a conclusion about classification is a process that requires expert judgment; it cannot now be reduced to a simple set of decision rules. However, we identify the kinds of information that can be useful in this process, and indicate how each might most appropriately be used.

Animals↗
PubMed1988

Dermal carcinogenic activity of petroleum-derived middle distillate fuels.

In general, the carcinogenic potential of petroleum-derived materials is related to the polycyclic aromatic hydrocarbon (PAH) content. Thus it has been assumed that liquids which boil below the PAH distillation range (i.e., below approx. 370 degrees C (700 degrees F) would not be carcinogenic. Several early studies supported this conclusion but were of relatively short duration. Several recent and more rigorous studies have shown that repeated application of certain petroleum-derived materials boiling between approximately 177-370 degrees C (350-700 degrees F) (i.e., middle distillate fuels) can produce tumors in mouse skin. The current studies assessed the tumorigenic potential of a series of middle distillates which varied with respect to boiling range, composition, and source of blending stocks. All of the samples produced evidence of weak tumorigenic activity which was characterized by low tumor yields and long median latencies. However, the majority of the tumor yields were significantly different from the control. There were no apparent differences in response among the samples. Thus the various parameters examined did not substantially influence tumor outcome. In particular, there was no association of tumorigenic activity with aromatic carbon content; this finding, coupled with evidence that PAH levels were low, suggested that the tumorigenic responses were not PAH-dependent. In addition to the tumors, there was evidence of non-neoplastic dermal changes including hyperplasia. These may have contributed to the tumorigenic responses; however, the actual mechanism of tumor induction is unknown.

Administration, Cutaneous↗
PubMed1987

A comparison of developmental toxicity evident at term to postnatal growth and survival using ethylene glycol monoethyl ether, ethylene glycol monobutyl ether and ethanol.

This study was designed to compare an abbreviated evaluation of uterine contents at term (teratology probe) with a modified Chernoff-Kavlock assay (postnatal study), [Chernoff N, Kavlock RJ: J Toxicol Environ Health 10:541-550, 1982]. Mice were intubated during gestation and were evaluated for signs of toxicity. In the teratology probe, uterine contents were examined at term. In the postnatal study, offspring were examined and weighed through day 22 postpartum. Ethylene glycol monoethyl ether (EGEE) produced embryo lethality and malformations, and decreased fetal weight at a dose level which was not maternally toxic in the teratology probe. In the postnatal study, EGEE decreased litter size and neonatal body weight; while litter size continued to decrease beyond the neonatal period, body weights of surviving pups were not significantly different from control. Pups exposed prenatally to EGEE developed kinked tail which was not apparent in fetuses or neonates. Maternally toxic dose levels of ethylene glycol monobutyl ether and ethanol were associated with increased embryo lethality in teratology probe studies. In postnatal studies, there were no significant effects on pup growth or survival at maternally toxic dose levels. Preliminary conclusions regarding maternal and developmental toxicity were comparable based on the teratology probe or postnatal study. Both assays measure litter size and offspring weight, but the teratology probe measures resorption incidence which may be a more sensitive index of prenatal death than number of live born. Neither fetal weight nor neonatal weight reliably predict permanent alteration of growth. A postnatal study permits detection of internal malformations or functional defects which reduce postnatal survival and gross abnormalities which appear postnatally.

Animals↗
PubMed1987

Evaluation of the dermal carcinogenic potential of liquids produced from the Cold Lake heavy oil deposits of northeast Alberta.

This study assessed the dermal carcinogenic potential of raw bitumen derived from the Cold Lake Oil Sands deposit (located in Northeast Alberta, Canada) and two liquids which were under evaluation as part of a process to refine the crude bitumen at the Cold Lake site. The crude bitumen was dermally carcinogenic, inducing tumors in 26% of the treated animals with a median latency of 106 weeks. This response was significantly greater than the tumor yield previously reported for a raw bitumen derived from Athabasca tar sands by the Syncrude process, but was not substantially different from the carcinogenic potential of two crude petroleum oils. The GO-FINING product, a high boiling (259-519 degrees C), catalytically cracked gas oil was a relatively potent dermal carcinogen, inducing tumors in 86% of the treated animals with a median latency of 46 weeks. This result is consistent with the fact that the GO-FINING product contained appreciable levels of high boiling aromatic compounds. The HYCRACKING product, a high boiling (102-498 degrees C), severely hydroprocessed liquid was noncarcinogenic. This result was also consistent with the compositional data; the high boiling components were predominantly saturated species. Thus the carcinogenic properties of the liquid products prepared by these two processes were as predicted from the compositional information.

Alberta↗
PubMed1986

Influence of housing conditions for mice on the results of a dermal oncogenicity bioassay.

Male C3H/HeJ mice were thrice weekly given 25 microliter applications of 0.25, 0.05, or 0.01% (w/w) benzo(a)pyrene (BaP) in acetone, or acetone alone, to clipped dorsal skin from 12 to 14 weeks of age for the remainder of their life spans. There were two groups of 40 mice for each treatment regimen, one group being housed in conventional stainless-steel wire mesh cages and the other in polycarbonate cages with wood shavings held in an enclosed ventilated cabinet. Under both housing conditions, tumor incidence was directly related and latency inversely related to BaP concentration. The time-adjusted incidence of epidermal neoplasms was significantly greater for the groups housed in polycarbonate cages. Mortality rates were directly related to BaP concentration and were significantly enhanced by the polycarbonate-cage housing conditions for the high and intermediate concentrations. Survival patterns for the two acetone control groups were similar. These findings indicate that differences in housing conditions can influence both the incidence and the latency of local neoplasms produced in response to the chronic application of a carcinogen in dermal oncogenesis bioassays.

Animals↗
PubMed1986

Evaluation of the dermal carcinogenic potential of tar sands bitumen-derived liquids.

The carcinogenic potential of Athabasca tar sands and six experimental liquids derived from crude bitumen was evaluated utilizing the mouse epidermal carcinogenesis model. Tar sands, bitumen, and untreated naphtha produced few, if any, tumors. Three thermally and catalytically cracked liquids, light (nominal boiling range: 149-316 degrees C) and heavy (nominal boiling range: greater than 316 degrees C) gas oils and gas oil blend (boiling range: greater than 316 degrees C), produced a significant number of epidermal neoplasms. A synthetic crude oil, prepared by blending naphtha and light and heavy gas oils, was moderately carcinogenic; however, the activity of this sample fell within the range of values obtained in studies of crude petroleum samples. Since the bitumen-derived streams do not differ substantially in carcinogenic potency from petroleum-derived materials of comparable boiling range and process history, industrial hygiene practices which limit exposures to levels comparable to those observed in the petroleum-refining industry should provide similar measures of protection.

Animals↗
PubMed1976

Psychosocial consequences of therapeutic abortion King's termination study III.

A follow-up study is reported of a consecutive series of 360 women who underwent termination of first trimester pregnancies by vacuum aspiration. Each patient received brief counselling before termination. Follow-up examinations were carried out by means of detailed, structured interviews at three months and between 15 months and two years (mean: 18 months) after termination. Outcome was assessed in terms of psychiatric symptoms, guilt feelings, and adjustment in marital and other interpersonal relationships, sexual responsiveness and work record. Compared with ratings of psychosocial adjustment before termination, significant improvement had occurred at follow-up in respect of psychiatric symptoms, guilt feelings and interpersonal and sexual adjustment; there was no significant change in marital adjustment. Adverse psychiatric and social sequelae were rare.

Abortion, Therapeutic↗
PubMed1976

Correlation of lead and cadmium in human urine.

A statistical evaluation of the relationship between elevated concentrations of lead and cadmium in human urine is presented. The importance of the 24-hour continuously collected urine sample is confirmed.

Cadmium↗