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Biomedical subjects

G A Fox

Publications and source records attributed to G A Fox.

32 records · Page 2Linked to original sources

Practical causal inference for ecoepidemiologists.

Environmental scientists and managers must determine whether a relationship between an environmental factor and an observed effect is causal and respond accordingly. Epidemiologists have, over the past 150 yr, developed a systematic approach to evaluating these relationships. Their criteria for objectively evaluating the relationship between a suspect cause and a chronic disease are (1) probability, (2) time order, (3) strength of association, (4) specificity, (5) consistency on replication, (6) predictive performance, and (7) coherence. These criteria can be used, with little modification, to evaluate associations in relation to diseases in fish and wildlife suspected to be caused by exposure to chemical pollutants. Some populations of fish and wildlife are members of the same guilds as subpopulations of humans. Investigations of chemically induced disease in these sentinel populations of fish and wildlife may identify the potential risks posed to these human subpopulations. Evidence evaluated using the epidemiologic criteria may assist environmental managers to determine whether a substantive case can be made to initiate preventative or remedial action. By applying the null hypothesis, scientists are forced to consider how much information must be ignored to conclude that a causal relationship does not exist.

Animals↗

Effect of social drinking on neuropsychological performance.

The effects of social drinking on neuropsychological function have been assessed in a group of healthy male volunteers. Subjects were divided into three groups according to their daily alcohol consumption: (1) 40 g or less (n = 93), (2) 41-80 g (n = 22), (3) 81-130 g (n = 16). Group 1 had been drinking at the present level for a mean of 12.6 years, group 2 for 16.9 years and group 3 for 15.1 years; the differences are not significant. There are no significant differences on any neuropsychological tests variables between groups 1 and 2. However, subjects in group 3 were found to perform at a significantly lower level than groups 1 and 2 on the Rey Auditory Verbal Learning Test, the Austin Maze, and the Little Man and Spatial Memory Tests of the Bexley Maudsley Automated Psychological Screening Test. The pattern of deficits found in heavy social drinkers is less severe but otherwise similar to that found in alcoholics.

Adult↗

Changes in plasma proteins in rats treated for short periods with hepatotoxins or with agents which induce cytochrome P450 isoenzymes.

We have compared the alterations in plasma proteins following treatment of rats with the centrilobular hepatotoxin carbon tetrachloride, the periportal hepatotoxin allyl alcohol and two inducers of hepatic microsomal drug metabolising enzymes, phenobarbitone and a mixture of polychlorinated biphenyls (Aroclor 1254). The results are compared with changes observed in animals treated with agents which caused proliferation of rat liver peroxisomes and described in an earlier publication. Our results indicate that: There is a marked induction of a minor glycoprotein which migrates as a prealbumin following treatment with both inducers of microsomal mixed function oxidases and inducers of peroxisome proliferation. There is a marked increase in a minor alpha 1-glycoprotein when there is chemically-induced mitosis in the liver but not in mitosis following liver damage. Two major alpha 1-glycoprotein are depressed in all forms of liver damage. There are indications of specific protein responses to allyl alcohol, to inducers of microsomal mixed function oxidases and to inducers of peroxisome proliferation.

1-Propanol↗

Toxicological investigations of pollutant-related effects in Great Lakes gulls.

Reproductive failure of a number of fish-eating birds was observed on the Great Lakes in the mid-1960s to mid-1970s. The herring gull (Larus argentatus) has been used as the primary monitoring species. The low hatching success observed in this species on Lake Ontario in the mid-1970s was due to loss of eggs and failure of eggs to hatch. Egg exchange experiments demonstrated that this was due both to the incubation behavior of adults and to direct embryotoxic effects. Decrease of nest attentiveness was demonstrated using telemetered eggs, but attempts to reproduce the embryonic effects by injection of pollutant mixtures into eggs were not successful. Reproductive success improved rapidly during the late 1970s and was normal by the end of the decade. Recent studies have focused on cytogenetic and biochemical changes and detailed analytical chemistry of residues. No changes in the rate of sister chromatid exchange over values determined in coastal colonies were observed. Elevation of hepatic aryl hydrocarbon hydroxylase activity, levels of highly carboxylated porphyrins, and changes of thyroid function have been found. The geographic pattern of these changes indicates that they are caused by xenobiotics, but it has not been possible to relate the changes to a specific chemical.

Animals↗

Tissue porphyrin pattern determination by high-speed high-performance liquid chromatography.

A rapid and sensitive method for the determination of porphyrin carboxylic acids in liver, kidney, and spleen by high-speed high-performance liquid chromatography is described. Porphyrins were extracted with recoveries greater than or equal to 98%, concentrated on disposable octadecylsilyl cartridges, and analyzed with a liquid chromatograph equipped with a 3 microns X 3 cm octadecylsilyl column and a fluorescence detector. Separation of di-, tetra-, penta-, hexa-, hepta-, and octacarboxylic acids was achieved within 5 min. The detection limits for uro, copro, and protoporphyrin were 20, 10, and 20 fmol, respectively.

Animals↗

The delay in polyhalogenated aromatic hydrocarbon-induced porphyria: mechanistic reality or methodological artefact?

Hepatic porphyria was induced in female Wistar rats exposed to dietary hexachlorobenzene (HCB) for 56 days. The well-documented several-week delay before liver total porphyrins became elevated was observed using conventional methods. However, a newly developed high-performance liquid chromatography (HPLC) technique revealed a much earlier response. Highly carboxylated porphyrins were found to increase soon after exposure to the toxicant. The long delay observed by total porphyrin analysis is shown to be due to the relatively small contribution of highly carboxylated porphyrins to the total porphyrin pool. It is concluded that the concept of a latent period is largely a methodological artefact which has confused the search for a fundamental understanding of chemically induced porphyria.

Administration, Oral↗

A quantitative assessment of thyroid histopathology of herring gulls (Larus argentatus) from the Great Lakes and a hypothesis on the causal role of environmental contaminants.

Thyroids from 213 adult herring gulls of both sexes were collected during incubation from nine colonies in the Great Lakes basin of eastern North America between 1974 and 1983, and from a single colony in the Bay of Fundy from 1977 to 1982. Qualitative and quantitative histological assessment revealed that the majority of the gulls from the Great Lakes basin suffered from goiter. These thyroids had a greater mass than those from the Bay of Fundy, and were microfollicular and frequently hyperplastic. The histopathology was similar to that previously observed in Pacific salmon from the Great Lakes. These findings are consistent wit a forage fish-borne goitrogenic etiology other than, or in addition to, iodine deficiency. Temporal and spatial differences in the severity of thyroid dysfunction are consistent with the hypothesis that polyhalogenated hydrocarbons are responsible for the goiter development and thyrotoxic effects observed in herring gulls from the Great Lakes area.

Animals↗

Avian endocrine responses to environmental pollutants.

Many environmental contaminants are hazardous to populations of wild birds. Chlorinated hydrocarbon pesticides and industrial pollutants are thought to be responsible for population declines of several species of predatory birds through eggshell thinning. Studies have demonstrated that these contaminants have estrogenic potency and may affect the functioning of the gonadal and thyroidal endocrine subsystems. Petroleum crude oil exerts toxicity externally, by oiling of plumage, and internally, by way of ingestion of oil while feeding or preening. Extensive ultrastructural damage to the inner zone of the adrenal, diminished adrenal responsiveness to adrenocorticotrophic hormone, and reduced corticosterone secretion rate suggest that low levels of plasma corticosterone reflect a direct effect of petroleum on the adrenal gland. Suppressive effects of oil on the ovary and decreases in circulating prolactin have been associated with impaired reproductive function. Large-scale field studies of free-living seabirds have confirmed some of the inhibitory effects of oil on reproduction that have been observed in laboratory studies. Organophosphorus insecticides, representing the most widely used class of pesticides in North America, have been shown to impair reproductive function, possibly by altering secretion of luteinizing hormone and progesterone. Relevant areas of future research on the effects of contaminants on avian endocrine function are discussed.

Adrenal Cortex↗