Biomedical subjects
B Walton
Publications and source records attributed to B Walton.
Effects of anaesthesia and surgery on immune status.
The immunological implications of anaesthetic practice relate to the possibility that exposure to anaesthesia and surgery, by depressing a variety of both non-specific resistance mechanisms and specific immune responses, renders patients more liable to infections and the spread of malignancy in the period after operation. A review of the literature suggests that, although various anaesthetic agents themselves depress immune responses, the effects are shortlived and of minor importance when compared with the effects of the hormonal aspects of the stress response. A more aggressive approach to relief of pain and anxiety may be beneficial from the immunological point of view.
Anaesthesia, surgery and immunology.
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A morphologic study of unexplained hepatitis following halothane anesthesia.
A survey of postoperative jaundice throughout the United Kingdom allowed the detailed analysis of 76 patients with unexplained hepatitis following halothane anesthesia ("halothane hepatitis"). In 16 patients liver biopsy specimens were examined by light and/or electron microscopy to determine whether the liver morphology could aid the differentiation between "halothane" and "acute viral" hepatitis. The mitochondrial changes often claimed to be characteristic of holothane hepatitis were unremarkable in our patients. Since lipid vacuolation and a predominantly centrilobular distribution of necrosis are not classically described in fatal viral hepatitis, the presence of these features in some of our fatal cases was of some diagnostic interest. In general, however, the results of light and electron microscopy in patients with unexplained postoperative hepatitis is considered to have little differential diagnositc value.
Unexplained hepatitis following halothane.
Full clinical and laboratory details of 203 patients with postoperative jaundice were submitted to a panel of hepatologists. All patients whose jaundice may have had an identifiable cause were excluded, which left 76 patients with unexplained hepatitis following halothane anaesthesia (UHFH). Hepatitis in 95% of these cases followed multiple exposure to halothane, with repeated exposure within four weeks in 55% of cases. Twenty-nine patients were obese, 52 were aged 41-70, and 53 were women. Thirteen patients died in acute hepatic failure. Rapid onset of jaundice after anaesthesia, male sex, and obesity in either sex were poor prognostic signs. Of the clinical stigmata of hypersensitivity, only eosinophilia was impressive. The UHFH group had a much greater incidence of liver kidney microsomal (LKM) and thyroid antibodies and autoimmune complement fixation than those patients whose jaundice related to identifiable factors. Thirteen of the 19 patients with LKM antibodies also had thyroid antibodies. In six patients retested two to three years later LKM antibodies had disappeared, although thyroid antibodies persisted. Rapidly repeated exposure to halothane may cause hepatitis, but such a complication is probably rare. Possibly obese women with a tendency to organ-specific autoimmunity may be more at risk. Nevertheless, the comparative risks of rapidly repeated halothane or non-halothane anaesthesia cannot be determined from the present data. If alternative satisfactory agents are available halothane should be avoided in patients with unexplained hepatitis after previous exposure, although in three to five patients with UHFH who were re-exposed to halothane jaundice did not recur.
Absence of cellular hypersensitivity in patients with unexplained hepatitis following halothane.
In-vitro tests of cell-mediated immunity were performed using blood obtained from subjects with unexplained hepatitis following halothane anesthesia to determine whether sensitization to potentially antigenic products of halothane metabolism might exist. Both lymphocyte transformation and leukocyte migration-inhibition tests were undertaken in the presence of trifluoroacetylated human serum albumin. All tests in the presence of these potential antigenic complexes were negative. The results support the view that cell-mediated hypersensitivity to trifluoroacetylated proteins does not contribute to the pathogenesis of hepatic dysfunction following halothane anesthesia.
[Does anesthesia have an immunosuppressive effect?].
Immune depression occurs after general anaesthesia. It is related to depression of serum factors after anesthesia with ether or chloroform, or secondary to depression of antibody-producing cells after anaesthesia with halothane, nitrous oxyde or Pentothal. This immune depression augments proneness to bacterial and viral infection and to malignant disease.
[Relevance of clinical signs of hypersensitivity in cases of halothane hepatitis].
142 patients with postoperative jaundice following anaesthesia with halothane were divided into two groups:-group A (76 cases) in which halothane appeared to be the sole responsible agent for jaundice, and- group B (66 cases) in which other causes were detected. The incidence of clinical signs considered to be specific for halothane-induced hepatitis (skin rash, arthralgia, bronchospasm, fever of unexplained origin, leukocytosis) was the same in both groups. Only a high eosinophil count was more common in group A. The author found a clear-cut relationship between the frequency of exposure and the onset of hepatitis as well as a shortening of the latent period with increasing numbers of exposures.
Effect of phenformin on gluconeogenesis from lactate and intracellular pH in the isolated perfused guinea pig liver.
Gluconeogenesis from lactate and hepatic cell pH (pHi) were measured in the isolated perfused livers of starved guinea pigs in the presence and absence of phenformin (phenethylbiguanide). The observed decrease in lactate consumption and glucose output in the presence of phenformin was associated with a fall in pHi. The fall in glucose output observed was considerably greater than accountable for by the decrease in lactate consumption. A possible mechanism for the pathogenesis of clinical lactic acidosis due to phenformin therapy is suggested.
Proceedings: Further immunological investigations in patients with possible halothane hepatitis.
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Effect of oxygen insufflation during one-lung anaesthesia.
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Immunological aspects of halothane hepatitis. Possible relevance of biotransformation.
The hypothesis that "halothane hepatitis" is related to hypersensitivity to the agent is widely accepted. The hypothesis is based, in part, on reports ostensibly demonstrating cell mediated immunity to halothane in such patients. These reports, however, are open to criticism and have not been confirmed. Halothane is unlikely to be capable of antigenicity in its own right, although reactive metabolites may be involved. We have further investigated cell mediated immunity in patient with alleged halothane hepatitis. Human serum albumin and liver specific protein were chemically trifluoroacetylated and these complexes were used as potential antigens in lymphocyte transformation and leucocyte migration inhibition tests. Using these in vitro indices, cell mediated immunity was not demonstrated in any of the patients studied. It is possible that other metabolites and/or carrier molecules may be involved, and that patients predisposed to autoimmune disease may be particularly at risk.