Biomedical subjects
Publications and source records attributed to M M Fisher.
The technique of external chest compression to assist expiration has been used in asthmatic patients for some years, but it has not been described in detail in the medical literature. We describe a method for assisted expiration and its apparent value in the emergency treatment of asthma. The technique requires further evaluation to determine its role in the resuscitation of asthmatics.
The performance of ten high-flow Bird blenders (3M Company) was assessed to ascertain the stability of the oxygen delivery both over time and within a single respiratory cycle. Blended oxygen concentrations were assessed for both continuous low flow and for intermittent flow with variable tidal volumes as is seen with mechanical ventilation. Studies were repeated after the addition of a high flow bleed from the blender via a T-piece. We observed clinically significant variations in the oxygen concentrations delivered by several blenders when the relationship between air and oxygen supply pressures varied. This variability was greatest when the air and oxygen pressures were nearly equal. When the line pressures were stable, mixed oxygen concentrations were constant but variations in oxygen delivery were found within individual breath cycles. This could be explained by postulating that at the initiation of flow from the blender a small pocket of unblended gas (pure air or pure oxygen) was issued by the blender before the balancing mechanism stabilised to deliver the desired oxygen concentration. This variability of oxygen delivery may have considerable impact on the measurement of oxygen consumption using the open circuit technique. The addition of a high flow bleed completely ablated this blender-derived variation in oxygen delivery.
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IgE antibodies that reacted with morphine and codeine were detected in the serum of a subject who experienced a life-threatening anaphylactic reaction following the administration of Omnopon-Scopolamine (papaveretum-hyoscine). Hapten inhibition studies with morphine and a number of structurally-related analogues revealed that morphine and codeine were the most potent inhibitors of IgE binding to a morphine-solid phase. Nalorphine, meperidine, and methadone were also good inhibitors of IgE binding, but naltrexone, buprenorphine, and fentanyl proved to be poor inhibitors. From a detailed examination of structure-activity relationships, the authors conclude that the important structural features of the morphine allergenic (that is, IgE binding) determinant comprises the cyclohexenyl ring with a hydroxyl group at C-6 and, most important of all, a methyl substituent attached to the N atom. The authors' findings suggest that morphine analogues administered to such a patient may provoke clinical anaphylaxis. Hyoscine reacted weakly with IgE antibodies in the subject's serum, but this was thought to be due to weak cross-reaction between this compound and morphine.
The development of acute renal failure increases the morbidity, the mortality and the duration of hospital stay of all patients who are treated in intensive-care units. Consequently, the prevention of renal failure, and especially that of oliguric acute renal failure, has a high priority in the management of patients who are seriously-ill. The identification of risk factors, the pretreatment of patients who are in high-risk categories and the maintenance of adequate hydration, oxygenation, cardiac output and renal blood flow are the first-line priorities in management. The use of loop diuretic agents, mannitol and dopamine, separately or in combination, probably are effective prophylactic measures. They also may have therapeutic benefit in the maintenance of a non-oliguric state in the presence of acute renal failure, although there is less scientific support for this role. Such manoeuvres are worthy of trial before an oliguric state is accepted. They are more likely to be efficacious if they are instituted early.
Anaphylactic shock may be provoked by a diverse group of substances and stimuli, which range from large molecular weight proteins and small drug molecules to some colloids, emulsions and even exercise. The underlying mechanism may be immunological or non-immunological but, regardless of the mechanism, the physiological effects and the observable symptoms of anaphylaxis are due to the release of potent pharmacologically-active mediators, including histamine. Although a number of predisposing factors are recognized, the appearance of most of the reactions cannot be predicted. Reactions occur suddenly and dramatically and progress rapidly. Cardiovascular collapse is the most common life-threatening clinical feature, while bronchospasm is the most difficult to treat. The primary aim of treatment should be to treat the underlying cause and to improve cellular oxygenation. The pharmacological agent of choice for treatment is adrenaline. It is direct-acting and is effective for both bronchospasm and cardiovascular collapse. It is imperative that the provoking substance or stimulus be identified in patients and there is no substitute for a carefully-gathered and detailed case history in the diagnosis of anaphylaxis. Patients should be issued with some form of warning identification together with written details concerning their reaction.
Profound myocardial depression developed in 2 patients after severe anaphylactic reactions following the induction of anaesthesia in 1 case and a bee-sting in the other. Neither patient had pre-existent cardiac disease. In both patients haemodynamic assessment, radionuclide ventriculography, and two-dimensional echocardiography confirmed the clinical impression of profound systolic myocardial dysfunction. Haemodynamic stability was attained by intra-aortic balloon counterpulsation, which was probably life-saving in both cases. Cardiac function improved rapidly although some contractile depression persisted for several days. At follow-up both patients had normal cardiac function with no evidence of underlying heart disease.
Transmission (thin sections and freeze-fracture replicas) and scanning electron microscopy were used to describe the nonparenchymal liver cells during the seven (1-7) stages of metamorphosis in the sea lamprey, Petromyzon marinus L., when bile ducts and canaliculi degenerate. The biliary atresia is accompanied by an increased diameter of fenestrae in the endothelium, an active phagocytosis by Kupffer cells in the sinusoids, and large lipid inclusions in perisinusoidal lipocytes (fat-storing or Ito cells). Plasma-like cells and foci of nonparenchymal cells (granulomas) are present in the liver interstitium during at least four stages of metamorphosis. The fenestrae in the sinusoidal wall are wider (up to 2.8-micron diameter) than normally reported for vertebrate livers but are likely a reflection of the morphogenetic and physiological events and consequences of the biliary atresia. Kupffer cells are involved in an extensive erythrophagocytosis, the storage of iron, and perhaps the incorporation of cellular components from hepatocytes. Lipocytes are the vitamin A-storing cells of the transforming liver and may be responsible for some perisinusoidal fibrosis. Granulomas are present during stages 3-6 and are focal areas where mononuclear leukocytes (lymphocytes and plasmalike cells), macrophages, and neutrophils have infiltrated the hepatic parenchyma. The function of the granulomas is not known; but their presence may be related to the porous nature of the sinusoidal wall, the tissue degeneration, and/or the physiological change (e.g., bile stasis) during biliary atresia.
The incidence of a history of allergy, atopy or asthma is greater in patients who undergo life-threatening clinical anaphylaxis to anaesthetic drugs. However, because the incidence is low, the presence of such a history is not a reliable predictor of the likelihood of a reaction in an individual patient, and does not indicate that the patient should be investigated or pretreated, or that the selection of drug(s) be altered to reduce the likelihood of a reaction.
Using an immunoassay developed for the detection of thiopentone-reactive IgE antibodies, the combining site specificities of such antibodies found in sera of patients who experienced life-threatening anaphylactic reactions to the drug were studied. The antibody combining sites from one patient were complementary to the region of the thiopentone molecule containing a thio group at position 2 of the barbiturate ring. The allergenic determinant recognized by IgE antibodies from another patient encompassed a secondary pentyl group and an ethyl group attached to position 5 on the other side of the barbiturate ring. Thus, it is already clear that there is more than one allergenic determinant on the thiopentone molecule with the capacity to provoke IgE formation and drug-induced allergic reactions.
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The three-dimensional structure of the bile ducts and their relationship to the blood vessels were studied in the larval lamprey by scanning electron microscopy of the intact tissue and of biliary and vascular casts. The intrahepatic gall bladder is situated in the cephalic portion of the liver and a cystic duct is connected to a straight intrahepatic common bile duct, which extends to the extrahepatic bile duct at the caudal end of the liver. Several smaller intrahepatic common bile ducts are connected directly to the intrahepatic common bile duct, are convoluted or serpiginous and are surrounded intimately by sinusoids. This arrangement enables the bile ducts to have increased surface area exposed to blood vessels. The functional significance of this arrangement is discussed with respect to the modification of bile through the transport of solutes and the similarity of this bilio-vascular relationship to the peribiliary vascular plexus of the mammalian liver.
The snake neurotoxins alpha-bungarotoxin (alpha-BGT) and beta-bungarotoxin (beta-BGT) which act at the neuromuscular junction, were found to bind to IgE antibodies directed against neuromuscular blocking (NMB) drugs in the sera of two patients who had experienced lifethreatening anaphylactic reactions to succinylcholine. alpha-BGT inhibited IgE-binding to a choline-Sepharose solid support in one patient better than the NMB drug alcuronium, choline, triethylcholine and beta-BGT. IC50s for alpha-BGT and succinylcholine were 16 and 10 nmol respectively for one patient and 34 and 6.0 nmol for the other. Recognition of the NMB drugs and alpha-BGT by the same antibody is the first demonstration of an antigenic similarity between these drugs and the protein toxin.
This paper describes the separation and characterization of several IgA fractions from the same human monoclonal source, based on their ability to bind secretory component (SC). The study was undertaken to elucidate features of the immunoglobulin-binding site for SC, and to examine the dependence of mucosal transport on IgA-SC interaction. Enrichment or depletion of SC-binding activity was accomplished on an affinity adsorbant made with SC from human colostral whey. The affinity-purified human IgA fractions contained IgA polymers and were 77% active in rebinding to the adsorbant; this activity was diminished significantly by direct radioiodination. The non-adherent IgA fractions contained both polymer and monomer, and were only 8% active in rebinding to the adsorbant. When the polymer and monomer components were separated from each other, the non-adherent polymer was found to resemble the affinity-purified fraction by all criteria examined including J-chain content, except that the SC-binding capacity was greater than five-fold lower. These findings have two implications for the SC-binding site on human IgA: first, the presence of J-chain is insufficient to bestow IgA with SC-binding activity; second, a critical tyrosine participates in maintaining the SC-binding region, possibly on the IgA heavy chain. The relationship between SC binding and mucosal transport was tested in the rat hepatobiliary model. All radiolabeled human IgA fractions were captured rapidly from blood by the rat liver, but only the SC-binding fractions underwent substantial intact transport to bile (greater than 70% of the injected dose). Even though a nominal proportion of the SC-non-adherent IgA appeared in bile (4-15% of the dose), most IgA in these fractions was rapidly degraded within the liver. Thus, only a small amount of monomeric and polymeric IgA can use alternative receptors to get to bile by diversion from the degradative pathway. Polymeric IgA can undergo efficient transport across the cell, strictly conditional on a high binding capacity for SC. This demonstrates that membrane SC is the receptor conferring specificity on the mucosal-transport pathway.