Perforation of bladder carcinoma presenting as acute abdomen.
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Biomedical subjects
Publications and source records attributed to M Gough.
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Normal human faeces and effluent from terminal ileostomies in patients with ulcerative colitis were collected. The results for ileostomy effluent given as g/24 h (mean +/- SD; n = 12) were as follows: wet weight, 897 +/- 120; total dry weight, 84 +/- 8; non-diffusible dry weight 46 +/- 5. The corresponding results for faeces (n = 6) were 104 +/- 24; 26 +/- 6; 19 +/- 5. Whereas approximately 15% of the total dry weight of ileostomy effluent appeared to consist of mucin-derived material, only trace amounts of such material could be detected in faeces.
Information about the possible human health effects of dioxin is available from studies of chemical plant workers, sprayers of dioxin-contaminated herbicides, and other exposed people. No human illness, other than the skin disease chloracne, which has occurred only in highly exposed people, has been convincingly associated with dioxin. Some epidemiologic studies have suggested associations between dioxin and stomach cancer, soft tissue sarcomas, and lymphomas, but other studies, powerful enough to detect excesses of those diseases, if they exist, have not done so. With the exception of one study of chemical plant workers that reported an excess of stomach cancer, all the suggested associations of increased cancer risks and dioxin exposures are from studies of herbicide applicators. Both direct measurements of the concentrations of dioxin in the body fat of chemical plant workers and the occurrence of chloracne in those men support the conclusion that they were exposed to far greater amounts of dioxin than herbicide applicators. Therefore, if the cancers found in herbicide users were associated with dioxin, even more of those cancers would be expected among the chemical plant workers; the expected increases are not found. In short, epidemiologic studies in which dioxin exposures are known to have been high, either because of the appearance of chloracne or from measurements of dioxin in exposed people, have failed to reveal any consistent excess of cancer. In those studies that have reported associations between exposure and disease, no chloracne was reported, and there are no measurements of higher-than-background levels of dioxin in the people who are classified as exposed.
A 1984 risk assessment identified 1 part per billion (ppb) of dioxin in soil as a "level of concern" at Times Beach, Mo. The authors of the assessment had to rely on many assumptions in their analysis, but since that time, a number of investigators have obtained data that bear directly on estimating exposures from substances in soil. Partly because of the assumptions and partly because of the site-specific nature of their analysis, the authors of the Times Beach risk assessment cautioned against the adoption of 1 ppb as a delineator between acceptable and nonacceptable levels of contamination. Those cautions have been more frequently ignored than honored, and 1 ppb has become a de facto standard. In November 1989, the Center for Risk Management at Resources for the Future hosted 50 experts at a workshop that heard and discussed published and new research about exposure estimates and measures. The 1984 assessment identified soil ingestion by toddlers as the single most important source of exposure to dioxin in soil; it assumed that toddlers ingested 10 g soil daily. Research discussed at the workshop shows that the average child ingests about 0.04 g soil daily, but that 1 of 320 studied children ingested 5 g. These findings leave open the risk management decision about whether acceptable exposure levels should be established to protect the average child or the extreme child. Furthermore, the absence of children from commercial and industrial sites led to suggestions that higher concentrations of dioxin are acceptable in soil at such sites. Some workshop participants objected to those suggestions because of the difficulty of assuring that such sites would not revert to residential use in the future. Whether deed restrictions are sufficient to prevent such reversions was seen as an important research topic. Workshop participants repeatedly discussed the importance of site-specific data in estimating exposures: Measured half-lives of dioxin in different soils range from 18 mo to greater than 100 yr; bioavailability from various soils differs by at least 20-fold; and the amounts of soil ingested by grazing cattle can differ 20-fold depending on conditions. Workshop participants agreed upon some suggestions for research and generally favored the development of guidelines for exposure assessment that would allow consideration of site-specific information. Furthermore, they generally agreed that no single concentration should be taken as a level of concern. Instead, levels should be established that consider the planned uses of the sites.
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The phenoxy herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is widely used to control the growth of weeds and broadleaf plants. We convened a panel of 13 scientists to weigh the evidence on the human carcinogenicity of 2,4-D. The panel based its findings on a review of the toxicological and epidemiological literature on 2,4-D and related phenoxy herbicides. The toxicological data do not provide a strong basis for predicting that 2,4-D is a human carcinogen. Although a cause-effect relationship is far from being established, the epidemiological evidence for an association between exposure to 2,4-D and non-Hodgkin's lymphoma is suggestive and requires further investigation. There is little evidence of an association between use of 2,4-D and soft-tissue sarcoma or Hodgkin's disease, and no evidence of an association between 2,4-D use and any other form of cancer. Scientists on the panel were asked to categorize 2,4-D as a "known," "probable," "possible," or "unlikely" carcinogen or as a noncarcinogen in humans. The predominant opinion among the panel members was that the weight of the evidence indicates that it is possible that exposure to 2,4-D can cause cancer in humans, although not all of the panelists believed the possibility was equally likely: one thought the possibility was strong, leaning toward probable, and five thought the possibility was remote, leaning toward unlikely. Two panelists believed it unlikely that 2,4-D can cause cancer in humans.
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Use of laboratory animal data to make quantitative predictions of the risks of toxic effects in humans assumes that a relationship exists between the potencies in animals and humans and that its parameters can be estimated adequately. Such "scaling rules" have been used to predict the risks of carcinogenicity or other effects. A survey of the literature yielded only a modest number of papers devoted to the validity of these interspecies risk extrapolations, of which approximately 25 attempt quantitative comparisons for either radiation or chemical hazards. Some authors have investigated relatively large data sets in an attempt to identify the scaling rule that provides the best correlation of risks in two or more species. Others have selected a scaling rule and investigated whether its predictions from data in laboratory species match the risks found in humans. Opinion is divided on the validity of specific extrapolation rules and the utility of animal experiments for quantitative risk assessment. Correlations exist among risk levels in various species, but many factors appear to influence toxicity that are not captured in a simple scaling rule such as dose per unit weight or per unit surface area. Although scaling rules are useful, better projections will be made if case-specific factors such as pharmacokinetics can be considered. Further careful comparisons of quantitative risk estimates are needed.
United States regulatory agencies use no-threshold models for estimating carcinogenic risks. Other countries use no-threshold models for carcinogens that are genotoxic and threshold models for carcinogens that are not genotoxic, such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD or "dioxin"). The U.S. Environmental Protection Agency has proposed a revision of the carcinogenic potency estimate for TCDD that is based on neither a threshold nor a no-threshold model; instead, it is a compromise between risk numbers generated by the two irreconcilably different models. This paper discusses the revision and its implications.
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Fructooligosaccharides are naturally occurring compounds that have been reported in a variety of plants. Neosugar is a fructooligosaccharide mixture of 1F-(1-beta-fructofuranosyl)-sucrose polymers which is produced on a commercial scale from sucrose using a fungal fructosyltransferase. The resulting product is 0.4 to 0.6 times as sweet as sugar and is resistant to digestion by mammalian alpha-amylase, sucrase and maltase. Although Neosugar is non-digestible in humans, it is selectively utilized by bifidobacteria. Neosugar has been examined extensively in human and animal studies which indicate a lack of toxicity, carcinogenicity and genotoxic effects. Neosugar is used as a feed additive for poultry and swine in Japan and has been approved in foods as a raw material. Additional studies in progress in the US suggest that it could provide an economic alternative as an additive to poultry and swine feed.
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1. The mucus glycoproteins in meconium from normal infants and from infants having cystic fibrosis with meconium ileus have been studied. 2. Whereas normal meconium contained about 50% protein-bound carbohydrate, the meconium from cystic fibrosis contained only about 10%. 3. Glycopolypeptides were prepared from the mucus of glycoproteins. The oligosaccharide units from this material were released and fractionated. The fractions ranged widely in size and composition. 4. The fractions from cystic fibrosis specimens had a significantly higher content of fucose than those from normal specimens.
The product of phage P22 gene c1 has two functions: (1) it promotes synthesis of repressor and (2) during the first minutes of infection it retards expression of some lytic genes. We call the second, negative function "c1 retardation". We investigated c1 retardation in a mutant host of Salmonella typhimurium that is resistant to rifampicin and carries an altered RNA polymerase. No c1 retardation of DNA synthesis was detectable in this host after infection with wild-type phages. This elimination of the normally detectable c1 function leads to the conclusion that the mutant RNA polymerase interferes with the expression of c1 gene activity. Wild-type genes form clear plaques on the mutant host. Mutants of P22 called cly were isolated by others. These mutants form turbid plaques on the altered RNA polymerase host. Infections with P22 cly in the mutant host resulted in detectable c1 retardation. The cly mutation therefore restores c1 activity in a host which wild-type c1 is not expressed. Two spontaneous mutants were isolated from the mutant host. These two strains allowed partial expression of c1 retardation, although they remained rifampicin resistant. We interpret our data to indicate that expression of the normal functions of the gene c1 product requires an interaction of that product with the host RNA polymerase.