Lung cancer and passive smoking.
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Biomedical subjects
Publications and source records attributed to N Mantel.
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Following a major environmental accident near Seveso, Italy, on July 10, 1976, we attempted to determine if the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) released into the atmosphere had any effect on the liver function and lipid metabolism of exposed children. From July 1976 to June 1982, we analyzed the results of more than 4500 laboratory tests (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, cholesterol, and triglycerides in plasma and delta-aminolevulinic acid in urine) in a population of about 1500 children aged 6 to 10 years at the moment of the accident. The children exposed to the highest concentration of TCDD showed alterations in serum gamma-glutamyltransferase and alanine aminotransferase activity compared with the control group. These differences were restricted to values inside limits set from the lower end of the normal range to slightly above it. The observed abnormalities were slight and disappeared with time.
A panel of 7 diagnostic cytopathologists, i.e., physicians trained to diagnose the malignant potential of human cells in Papanicolaou-stained smears, was asked to evaluate two sets of microscope slides of stained coverslip preparations of 28 cell culture lines, 15 of which were neoplastic. Slide Set I consisted of 13 pairs of cell lines, one member of each pair being nontumorigenic and the other tumorigenic; the lines were of mouse (9 pairs), rat (3 pairs), and human (1 pair) origin. Slide Set II contained 4 human lines: one lung cancer, one melanoma, and two fibroblast lines. Of a total of 114 diagnostic decisions by the panel, 88 were correct (66/86, 77%) in choosing which member of a pair was neoplastic and 22 were correct (22/28, 79%) in choosing whether a given individual human line was or was not neoplastic. Two members of the panel were correct more frequently, with 16/17 (94%) correct diagnoses, each. Five nuclear morphologic criteria of malignancy used by cytopathologists were prominent in the tumorigenic lines: altered chromatin pattern characterized by increasing size of chromatin granules and chromatin clumping, sharp angularity of large nucleolar and/or chromocenter borders with spicule formation (pointed projection), irregular parachromatin clearing (increase in the clarity of the clear spaces between chromatin threads, granules and clumps), uneven thickness of chromatin at the nuclear border, and variability in nuclear size and shape from cell to cell. These markers of neoplastic transformation, when added to those previously reported, should increase overall accuracy in the diagnosis of neoplastic transformation of mammalian cells in culture.
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A previous study of twins with Parkinson's disease (PD) revealed low concordance, suggesting that genetic factors play a minor role in the etiology of PD. To identify possible environmental determinants of PD while maximally controlling for hereditary factors, 31 monozygotic twin pairs discordant for PD were interviewed by telephone. Information about possible risk factors was obtained from systematic and uniform interviews with cases and controls. The only statistically significant result was less cigarette smoking by PD patients (p less than 0.05). Thirteen dizygotic discordant twin pairs were evaluated with the same techniques, but there were no statistically significant differences between affected and unaffected twins.
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5-Fluorouracil was used in the treatment of a recently established. human adenocolon carcinoma implanted in the subrenal capsule site of athymic mice as part of a program to determine the relative effectiveness of antitumor agents in the treatment of human tumors grown as xenografts and in the clinic. 5-Fluorouracil treatments resulted in a dose-dependent inhibition of tumor growth under the two examined schedules (five daily doses and three doses every 4 days) when administered either i.v. or i.p. The various schedules and routes resulted in similar patterns of antitumor effects when the data were based on the endpoints of either final tumor weight, change in tumor weight, or relative tumor weight. Assessments of cell viability based on histological examination of tumored kidneys resulted in a downward displacement of the dose-response curves but did not alter their shape or the interpretation of the data. Although approximately 1-mm3 tumor fragments were implanted, variability of size was allowed. Tumor growth was not dependent on the initial size of the implant, as shown by a comparison between the initial individual or average tumor sizes and the final individual or average tumor sizes, respectively. The antitumor effects of the 5-fluorouracil could have been determined on the basis of final tumor weight alone. The inhibition of tumor growth was accompanied by weight loss in treated mice as compared with controls. At lower doses, however, the weight loss of the mice was not extensive, which indicated that the inhibition of tumor growth was, at least in part, attributable to some selective antitumor action of the 5-FUra. The greatest inhibition of tumor growth, however, was accompanied by the most extensive animal weight loss. This correlation raised the question of the degree to which the tumor growth inhibition observed was a consequence of nonspecific drug toxicity to the host. The current results stress the importance of detailed investigations into the nature of host-tumor parameters in order to assess the antitumor activity of candidate drugs in the treatment of human tumor xenografts.
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Cohort studies have particular advantages in confirming results of retrospective or case-control studies in those situations in which case-control studies are no longer feasible. In circumstances, the cohort study may involve randomization, thus reducing selection bias, but ordinarily there will have been self-selection by individuals as to the group in which they will fall. Investigators should analyze data from a cohort study so as to take the passage of time into account. Variables anticipated to have effects should be accounted for by stratification, if feasible, or by mathematical modeling, if necessary. Results should be interpreted with care, and qualifications should be made on any interpretations, including qualifications relating to the propriety of the mathematical model used. When long latencies are a factor, and particularly when exposure is initiated late in life, establishment of a positive role for the exposure can be difficult. Case-control and other epidemiologic studies are biased toward identification of exposures leading to outcomes of a unique nature but fail to identify more serious exposures with adverse outcomes which are more commonplace.
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