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Biomedical subjects

M M Fisher

Publications and source records attributed to M M Fisher.

At least 55 records · Page 3Linked to original sources

Diagnosis of IgE-dependent anaphylaxis to neuromuscular blocking drugs, thiopentone and opioids.

Although allergenic cross-reactivity of neuromuscular blocking drugs (NMBDs) is recognised clinically and has been firmly established at the serological and immunochemical levels, interpretation of in vitro inhibition findings for clinical purposes is not always straightforward. Points to be taken into account when considering serum IgE direct binding and inhibition results and when determining which NMBDs a patient may be sensitive to, include the relationship between in vitro potencies and clinical findings and the nature of the drug solid phase used for testing. It should also be remembered that the stimulating antigenic source for the patients' NMBD-reactive IgE antibodies is almost always unknown. A comparison of skin and IgE radioimmunoassay (RIA) tests for NMBDs in 29 patients is presented and difficulties involved in interpreting the results of both tests are discussed. Methods for increasing the detection of NMBD-reactive IgE antibodies are outlined. In screening sera of patients for IgE antibodies to thiopentone and morphine as well as NMBDs, multiple drug reactivities have been detected in a few subjects. Attention is drawn to defects in the existing thiopentone RIA although it is clear that the test is specific in patients who react to the drug. Addition of the serum tryptase assay to skin tests and IgE RIAs for NMBDs, thiopentone and morphine provides a powerful combination of diagnostic tests for the investigation of anaphylactoid reactions to anaesthetic drugs.

Anaphylaxis↗

A comparison between direct and calculated oxygen saturation in intensive care.

We investigated the discrepancy between calculated and spectrophotometrically determined oxygen saturation, and the corresponding effect of this difference on calculated oxygen uptake in 46 arterial-venous sample pairs from 28 critically ill patients. The range of discrepancy between the two methods showed limits of agreement (mean +/- 2SD) of -2.26 to +0.70% for arterial samples, and -5.52 to +4.96% for the corresponding venous samples. The effect of this variation on oxygen uptake showed limits of agreement of -43.2 to 36.0 ml/min when the discrepancy between oxygen uptake, calculated using the direct measure of saturation, was compared to that using the derived value. Multiple regression analysis showed that PCO2, temperature and 2,3 diphosphoglycerate were significantly related to saturation discrepancy with an R-squared value of 0.64 (P < 0.0001) for a subgroup of 25 venous samples. The precision of the PO2 electrode was also found to be a major contributory component to the discrepancies, particularly at venous PO2 values. Thus the use of calculated oxygen saturation may result in clinically significant inaccuracies in the assessment of some oxygen flux variables.

2,3-Diphosphoglycerate↗

A comparison of patients with illness phobia and panic disorder.

Fourteen subjects with illness phobia, a subtype of hypochondriasis, were compared with an equal number of subjects with panic disorder who had been matched for age and sex. The illness phobic subjects differed from panic subjects in not having spontaneous panic attacks or agoraphobic symptoms, the characteristic features of panic disorder. The onset of illness phobia was related to experience with illness in half the subjects. Half of the illness phobic subjects also had family histories of anxiety disorders. The results suggest that illness phobia is distinct from panic disorder and that it is a disorder in which environmental and genetic factors are etiologically important.

Adult↗

The 'cuff-leak' test for extubation.

The 'cuff-leak' test, which involves demonstrating a leak around a tracheal tube with the cuff deflated, has been advocated to determine the safety of extubation in patients with upper airway obstruction. In 62 such patients we were able safely to extubate all patients with a cuff leak. Two patients extubated without cuff leak required reintubation and in five patients who repeatedly failed the test, tracheostomy was performed. Subsequently, we extubated 10 patients who were stable on spontaneous ventilation and did not have cuff leak; three later required tracheostomy and seven were uneventfully extubated. While the presence of cuff leak demonstrates that extubation is likely to be successful, a failed cuff-leak test does not preclude uneventful extubation and if used as a criterion for extubation may lead to unnecessarily prolonged intubation or to unnecessary tracheostomy.

Airway Obstruction↗

Persistence of allergy to anaesthetic drugs.

Intradermal testing and RIA testing for specific IgE antibodies to neuromuscular blocking drugs (NMBDs) were performed in patients referred to an Anaesthetic Allergy Clinic. Six patients were initially investigated four to 29 years after clinical anaphylaxis during anaesthesia and two of these patients and sixteen others were investigated by intradermal testing on two occasions at least four years apart. Seven patients had RIA tests for NMBD-specific IgE antibodies on two occasions at the time of skin testing. In all but two patients the evidence for drug-specific antibodies persisted 4-29 years after the reactions. In one patient all tests became negative and in another the skin test became negative but the positive RIA persisted. Evidence of antibodies to NMBDs persisted in 21 of 22 patients who had had anaphylactic reactions to these drugs during anaesthesia. In the absence of evidence of allergy diminishing with time in the majority of patients it would seem wise to avoid drugs responsible for reactions for the rest of the patient's life.

Alcuronium↗

Heparin-induced thrombocytopaenia complicated by bilateral adrenal haemorrhage.

Acute adrenal insufficiency due to bilateral adrenal haemorrhage is an important clinical diagnosis and its association with heparin-induced thrombocytopaenia is infrequent. We report on a patient in whom life threatening acute adrenal insufficiency occurred consequent to such an association. The clinical manifestations simulated septic shock, highlighting the need to consider specifically acute adrenal insufficiency in such settings, and institute therapy promptly prior to obtaining results of confirmatory tests.

Adrenal Gland Diseases↗

Withdrawing and withholding treatment in intensive care. Part 1. Social and ethical dimensions.

Intensive care is an expensive resource. The medical profession has been criticised for applying technology indiscriminately and at vast expense to a relatively small group of patients. The desire of governments to reduce the cost of health care has made rationing of health services a topic of open discussion rather than an implicit activity as it has been in the past. The appropriate response of doctors to these problems is to provide leadership in promoting public awareness and debate of the effects of rationing, and to provide rational allocation of therapy to individual patients. The major issues involving resource allocation in society and to individuals are discussed.

Australia↗

Withdrawing and withholding treatment in intensive care. Part 2. Patient assessment.

In order to allocate resources fairly in intensive care units, and to avoid treatment which only prolongs dying, accurate prediction of outcome is necessary. Most systems that have been developed to predict the outcome of treatment are flawed and are little better than the guesses of experienced medical and nursing staff. The likelihood of survival must then be weighed against a subjective assessment of quality of life. The perception that intensive care wastes resources on patients who have little chance of survival should be reassessed in the light of our limited ability to detect hopelessly ill patients before embarking upon treatment.

Australia↗

Withdrawing and withholding treatment in intensive care. Part 3. Practical aspects.

A major goal of intensive care units should be to provide an environment in which death may occur with dignity if cure is impossible. The key issues in providing such an environment are the establishment of consensus that cure is impossible, and the provision of a resource person who has been a major participant in efforts to cure the patient. This person leads discussion with the patient or relatives, seeking concurrence rather than permission when the withdrawing or withholding of care is under consideration. We present problems which may arise in facilitating a dignified demise, and a practical approach to these problems.

Critical Care↗

Immunoassays employing substituted ammonium compounds other than neuromuscular blocking drugs to increase the detection of IgE antibodies to these drugs.

Subjects who experience life-threatening anaphylactic reactions to neuromuscular blocking drugs frequently have serum IgE antibodies that react with substituted ammonium groups on the drugs. Failure to detect drug-reactive antibodies may be due to the nature of the drug-solid support used for testing sera. With this in mind, solid phases of some selected compounds containing substituted ammonium groups, in particular triethylamine and morphine, were prepared and used to screen sera in an attempt to increase the frequency of detection of IgE antibodies complementary to tertiary and/or quaternary ammonium groups. For subjects who experienced an anaphylactic reaction to succinylcholine or gallamine, use of the supplementary assays increased the frequency of detection from 83 to 100%. For d-tubocurarine and alcuronium, detections increased from 92 to 100% and from 67 to 88%, respectively. Molecular models revealed a clear structural similarity between the conformations of the trialkylammonium groups on one face of the molecules of morphine and d-tubocurarine.

Anaphylaxis↗

The molecular basis of IgE antibody binding to thiopentone. Binding of IgE from thiopentone-allergic and non-allergic subjects.

Thiopentone-specific IgE antibodies from the sera of subjects who experienced a life-threatening anaphylactic reaction to the drug and IgE antibodies that cross-react with thiopentone via substituted ammonium groups in either cyclic or acyclic form, were studied by direct binding immunoassays and quantitative hapten inhibition methods. Findings provided an explanation for the apparent 'non-specific' nature of some IgE antibody reactions with thiopentone and reinforce the conclusion that the thiopentone IgE immunoassay is a valuable aid in the diagnosis of immediate allergic reactions to the drug.

Anaphylaxis↗

What rate of infusion of intravenous nutrition solution is required to stimulate uptake of amino acids by peripheral tissues in depleted patients?

We examined the effect of varying the quantities (0, 0.1, 0.2, 0.3, and 0.4 gN.kg-1.[day]-1) of nitrogen input on N balance, 3-methylhistidine (3MH) excretion, plasma amino acid concentration and the net flux of amino acids across the leg in depleted patients requiring parenteral nutrition. The calorie-to-nitrogen ratio was 140 to 1 (kcal:1 gN) and consequently the patients received varying amounts of calories (8, 14, 28, 42, and 56 kcal.kg-1.[day]-10. There was negative nitrogen balance and net loss of amino acids from the limb during fasting. An infusion of 0.2 gN.kg-1.[day]-1 of IVN reversed the net catabolic process and resulted in equilibrium of peripheral total amino acid flux and of tyrosine flux without a decrease in 3MH excretion. Net uptake of total amino acids and tyrosine in peripheral tissues was achieved with 0.4 gN.kg-1.[day]-1 and 56 kcal.kg-1.[day]-1. This was associated with a fivefold increase in 3MH excretion (p less than 0.01), indicating that net anabolism occurred with increased protein turnover. Fifty per cent of the amino acids taken up by peripheral tissues during infusions of 0.4 gN.kg-1.[day]-1 was due to the uptake of glutamate (Glu) and 20% was due to the uptake of branched chain amino acids (BCAA). Plasma Glu concentration, [Glu], did not increase with increasing IVN infusion, but BCAA concentrations did. Although the mean plasma [Glu] did not change with IVN infusion, there was an independent effect of plasma [Glu] (p less than 0.0001) and of N input (p less than 0.0001) on Glu flux, indicating that even at high infusion rates the maximal capacity of peripheral tissues to take up Glu had not been reached.

Amino Acids↗

Hepatic microvascular changes associated with development of liver fibrosis and cirrhosis.

Quantitative data defining basic microvascular parameters are needed for better understanding of the relationship between liver blood flow and function under normal and pathological conditions. The present study was undertaken to quantitate the following microvascular parameters: flow velocities in sinusoids and terminal hepatic venules; the range of sizes of terminal hepatic vessels; and acinar sizes in both normal rat livers and during the development of liver cirrhosis. Fibrosis and cirrhosis were induced by either weekly administration of carbon tetrachloride (CCl4) or by choline-deficient diet. Microcirculation was observed using intravital epifluorescent video microscopy and recorded on a videotape for subsequent analysis. It was found that even early stages of liver disease, when only mild hepatic fibrosis was present, are associated with profound changes in the hepatic microvasculature. These changes include the appearance of highly fluorescent cells in the liver parenchyma (mainly in the areas where collagen is being deposited), a marked dilatation of the terminal hepatic venules, an increase in hepatic venous outflow, and appearance of sinusoids with very high flow velocities. As fibrosis progresses to cirrhosis, the proportion of these "fast sinusoids" increases from 7% in fibrotic livers to 33% in cirrhotic livers. These results demonstrate the presence of functional intrahepatic shunts in cirrhotic livers and support the hypothesis that hyperdynamic splanchnic circulation may be an important factor in the etiology of portal hypertension in liver disease.

Animals↗

Urban envenomation.

Over a 12-year period, 61 patients were admitted to a metropolitan hospital on 67 occasions with envenomation from snakes, spiders, ticks or bees. We describe the epidemiology of the bites and the patient's response to treatment. First aid was used in only 50% of patients with potentially-lethal bites. All patients who developed severe envenomation showed symptoms within 30 minutes, and all patients survived.

Adolescent↗