Biomedical subjects
Publications and source records attributed to D Thomas.
The Derbyshire pharmaceutical computer system has been developed in collaboration with UniChem to give better stock control and thus make savings in the total drug bill. It is described by Mike Cullen, area pharmaceutical officer, and David Thomas, finance officer, South Derbyshire HD.
Hydroxylation of Aniline by haemoglobin immobilized as cross-linked soluble polymers and insoluble particles was studied. Activity yields after immobilization as well as kinetic constants were estimated. Hydroxylase activities similar to liver microsomal cytochrome P450 activities were obtained.
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The systolic ankle pressure response to thigh cuff occlusion (reactive hyperemia test) was compared with a similar measurement after treadmill exercise in 48 limbs of 24 normal volunteers. The reactive hyperemia test was then performed on 26 legs in 16 patients with clinical evidence of arterial disease of the leg and abnormal treadmill tests (mean decrease 39 +/- 24 percent). No decrease in pressure occurred in normal subjects after exercise. All control subjects demonstrated a decrease in pressure after thigh cuff occlusion (34 +/- 7.9 percent). The percent pressure decrease during reactive hyperemia in the abnormal group was significantly lower (49.7 +/- 19 percent; p less than 0.001). There was a high correlation between the percent decrease in pressure during reactive hyperemia and the decrease after exercise in the claudicants (r = 0.69; p less than 0.001). However, the percent pressure decrease in 13 of the 26 abnormal patients fell within 2 standard deviations of the reactive hyperemia control group mean. The range of the pressure decreases in these 13 patients, 16 to 48 percent, was shared by 47 of the 48 normal subjects. The findings in this study are inconsistent with those in previously published reports and suggest that reactive hyperemia testing cannot be used interchangeably with the treadmill exercise test.
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Interactions between the ionic detergent Sarkosyl (sodium lauroyl sarcosinate), Mg2+ ions, and the Spiroplasma citri cell membrane were analyzed microscopically and electrophoretically. Studies were performed under conditions where membrane proteins were apparently not released from the membrane by the detergent (molar ratio of MgCl2/Sarkosyl = 0.5). Although the S. citri membrane interfered with the crystallization phenomenon to some extent, the formation of Sarkosyl-Mg2+ crystals occurred regardless to the sequence of addition of the three components. Concomitantly the structure of the membrane disintegrated and membrane components were adsorbed to the crystal surfaces. The membrane protein fraction bound to the crystals was composed of the majority of the putatively intrinsic polypeptides, including the amphiphilic protein spiralin, and several extrinsic polypeptides. The polypeptide compositions of M-bands (crystal fractions loaded with membrane material) prepared from S. citri cells and from isolated S. citri membranes were similar, as shown by sodium dodecyl-sulfate electrophoresis and crossed immunoelectrophoresis. These results show that, the S. citri cell membrane, in contrast to bacterial membranes, is not protected from the effect of Sarkosyl by Mg2+ ions.
A computerized analysis of prognostic variables was performed in 96 proven cases of extrahepatic bile duct carcinoma treated over a 24-year period at UCLA. Forty-nine percent of the lesions were in the upper third of the bile ducts and 47% of these were resected, for an operative mortality rate of 23% and a maximum survival rate of 4.5 years. Palliative procedures in this region were associated with a 16% mortality rate and maximum survival rate of three years. The patients whose lesions were in the middle third suffered no operative mortality rate for resection or palliation and had a 12% five-year survival rate, with the longest survivor lasting 11 years. In the lower third lesions, 67% were resected by Whipple's procedures, for an 8% mortality rate and a five-year survival rate of 28% extending to nine years. Resection of these difficult carcinomas offers the best hope of survival but must be weighed against the high operative mortality risk in those lesions located in the hilar region.
A comparison was made of two anaesthetic techniques for outpatient dental surgery; the basis for comparison was symptomatic morbidity. One group of patients was managed with spontaneous breathing of nitrous oxide, oxygen and halothane; the other was ventilated mechanically, and received fentanyl and alcuronium. The latter anaesthetic was associated with a significantly higher incidence of morbidity on the day of operation, but not subsequently. The incidence of dysrhythmias was not significantly different. The comfort and safety of patients are discussed in relation to the choice of anaesthetic.
Phosphofructokinase was immobilized within a protein membrane or on soluble protein polymers using glutaraldehyde as cross-linking reagent. The native enzyme was also modified chemically, using the cross-linking reagent alone. A comparative kinetic investigation of these preparations was carried out. The catalytic activity of the chemically modified enzyme and its affinity towards fructose 6-phosphate decreased significantly; the modified enzyme lost its cooperative properties and the allosteric regulation by AMP was affected. When the chemical treatment was performed in the presence of effectors (AMP or ATP) the allosteric transition induced by AMP was restored, suggesting that the cross-linking reagent modified the AMP regulatory sites, albeit no higher-substrate-affinity enzyme conformation was frozen. Molecular data showed that glutaraldehyde produced intramolecular then intermolecular bonds as its concentration increased. When the enzyme was immobilized into protein membranes or on soluble polymers, the enzyme behavior was quite similar: decrease of affinity towards fructose 6-phosphate but no changes in cooperative properties and modifications of allosteric transition induced by AMP. When AMP was present during the immobilisation process, the enzyme immobilized in this way was no longer sensitive to effectors, either AMP or ATP. It showed Michaelian behavior and higher substrate affinity quite similar to that of the native enzyme. The data suggested that a higher-substrate-affinity enzymatic form was most probably stabilized by immobilization.
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The effects of hypoxemia on inspiratory muscle fatigue were assessed in 4 normal subjects. They breathed to exhaustion through high inspiratory resistances producing an inspiratory mouth pressure (Pm) of about 80% of maximal mouth pressure. The endurance time (tlim) during hypoxia (13% O2) was found to be shorter than that while breathing room air at equal inspiratory mouth pressures. Endurance time during hypoxia was also compared with that while breathing room air at equal rates of energy consumption (C), assuming that C is proportional to: Formula: (See Text). At these equal rates, endurance time during hypoxia still remained shorter than that during normoxia. Fatigue was also assessed by measuring the electromyographic power spectrum of the diaphragm and the parasternal intercostals. The power spectrum shifted towards low frequencies during fatigue and a greater rate of shift was observed under hypoxic conditions. The rate of lactate production during hypoxemia was greater than that during normoxia; however, blood lactate concentrations at the end of the tests were similar under both conditions. It was concluded that respiratory muscles, working against high inspiratory resistances, fall as pressure generators sooner during low oxygen breathing. The effect of low oxygen breathing on inspiratory muscle fatigue resulted in a shorter endurance time, a faster rate in the shift of the electromyographic power spectrum, and a greater rate of increase in blood lactate concentrations.
The cytochemical demonstration of acetylcholinesterase is theoretically and experimentally evaluated with a model system. The model is an artificial proteic membrane in which acetylcholinesterase homogeneously is immobilized chemically by a bifunctional agent, glutaraldehyde. The copper-thiocholine histochemical method is studied kinetically and the system is simulated by computer calculations based on experimental kinetic parameters and numerical analysis methods. In addition, the corresponding electron micrographs are presented. These studies lead to the conclusions that the system is ruled by diffusional constraints and that enzyme distribution and repartition of the insoluble electron dense product are not circumscribed by any specific conditions.
Laboratory study fo 109 insulin-dependent diabetics younger than 17 yr of age and resident in greater Montreal at the time on onset of symptoms is reported. The cases were diagnosed during a 2-yr period (1976-1978). Sibling controls were obtained for 72 of the cases studied. Viral titers to coxsackie B, rubella, and mumps virus for the 72 patient-sibling pairs showed no difference in geometric mean titers or in change of titer between samples taken at the time of diagnosis and those taken 28 days later. The incidence of positive islet cell antibody in teh IDdM cases was 68.0% at the time of diagnosis compared with 56.(% 4 wk later. The comparative figures of sibling controls were 4.2% and 1.4%, respectively. The frequency of HLA B8, B15, B18, and B7 antigens were compared both with the sibling controls and a normal control population. Pairing of high risk HLA antigens were found more frequently in cases than controls. There was no difference in geometric mean viral titers in cases with risk risk haplotypes compared with those cases in which such haplotypes were absent.
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The case of a 46 year old man with systemic mastocytosis with myocardial and pericardial involvement confirmed histologically after open biopsy is reported. The patient presented with skin, bone and medullary lesions and, in addition, with atrioventricular block and pericardial effusion. The possible mechanisms of the atrioventricular conduction defect are examined in the light of the physiological role of the mastocyte and research into the action of histamine on the myocardium. In particular, the negative dromotropic effect of histamine and fibrosis formation related to the mastocyte's function of connective tissue regeneration are discussed. This case, though rare, should alert the clinician to the possibility of myocardial and pericardial involvement in patients with mastocytosis. Further study into the effects of histamine on myocardium under physiological and pathological conditions is required.