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Biomedical subjects

W J Murray

Publications and source records attributed to W J Murray.

At least 55 records · Page 3Linked to original sources
PubMed1985

Efficacy and safety of low-molecular-weight heparin (CY216) in preventing postoperative venous thrombo-embolism: a co-operative study.

The efficacy and safety of a low-molecular-weight (LMW) heparin fraction in preventing postoperative venous thrombo-embolism, was assessed in a double blind, randomly allocated trial, and in an 'open' study. Of 395 patients included in the double blind trial, 199 received unfractionated (UF) calcium heparin, and 196 the LMW heparin fraction. The data were analysed on an 'intention to treat' basis. The two groups were well matched for risk factors which could predispose to the development of venous thrombosis. Fifteen (7.5 per cent) of one hundred and ninety-nine patients receiving UF heparin, and five (2.5 per cent) of one hundred and ninety-six patients in the LMW heparin group developed DVT (P less than 0.05). There was no significant difference between the two groups in terms of excessive incisional or total blood loss during surgery, postoperative drainage or wound haematoma formation. Of 910 patients included in the 'open' study who received a single injection of LMW heparin every day, 30 (3.2 per cent) died during the postoperative period; in none of the autopsied patients were pulmonary emboli detected. Thirty-one (3.4 per cent) patients developed isotopic DVT; twenty-seven (2.9 per cent) were receiving prophylaxis at the time the DVT was diagnosed. Thirty-six (3.9 per cent) patients developed wound haematoma; twenty-five (12.4 per cent) of those were in the two hundred and one undergoing surgery for gynaecological conditions, and eleven (1.5 per cent) in the seven hundred and nine patients having general abdominal surgery. This difference is statistically significant (P less than 0.001). The results of a double blind trial indicate that a single daily injection of 1850 APTT units (7500 antifactor Xa units) of a LMW heparin is more effective than 10 000 APTT units of commercially available UF heparin in preventing postoperative DVT. The findings of the 'open' study suggest that this regimen also provides an effective prophylaxis against post-operative major pulmonary embolism.

Adult↗
PubMed1985

Dietary selenium, glutathione peroxidase activity, and toxicity of 2,3,7,8-tetrachloro-dibenzo-p-dioxin.

TCDD has been shown to inhibit selenium-dependent glutathione peroxidase activity. The role of selenium in TCDD toxicity is not known. We have therefore examined the effect of TCDD administration on hepatic glutathione peroxidase, aryl hydrocarbon hydroxylase, glutathione reductase, and glutathione S-transferase activities, glutathione content, and lipid peroxidation in rats fed 0, 0.10, and 2.0 ppm dietary selenium. TCDD treatment significantly inhibited selenium-dependent glutathione peroxidase in animals on diets containing 0.10 and 2.0 ppm selenium. The selenium-dependent glutathione peroxidase activities in rats on 0.10 and 2.0 ppm dietary selenium were 8.3-and 4.7-fold greater than in animals fed a diet containing 0 ppm selenium. TCDD administration enhanced hepatic microsomal lipid peroxidation by factors of 4.0, 4.9, and 9.8 in animals fed diets containing 0, 0.10, and 2.0 ppm selenium, respectively. The administration of a lethal dose of TCDD to rats fed diets containing 0, 0.10, and 2.0 ppm selenium resulted in 0, 46, and 7% survival, respectively, after 66 d. Aryl hydrocarbon hydroxylase, glutathione S-transferase, and glutathione reductase activities were induced by TCDD. The results indicate that optimum dietary selenium provides partial protection from the toxic effects of TCDD.

Animals↗
PubMed1985

Heparin and dihydroergotamine prophylaxis against thrombo-embolism after hip arthroplasty.

A prospective study involving 500 consecutive patients undergoing hip replacement was performed to find out whether a combination of heparin and dihydroergotamine was effective in preventing postoperative fatal and non-fatal emboli. Deep-vein thrombosis was demonstrated in 131 cases (26.2%), in 99 of whom thrombi were confined to the ipsilateral (operated) limb and in 13 to the contralateral limb; 19 patients developed bilateral thrombi. Nine patients (1.8%) died during the first four weeks after operation, before they were discharged from hospital; in one, major emboli were demonstrated in the right pulmonary artery. Three of the 500 patients developed non-fatal pulmonary emboli. Excessive bleeding occurred in 21 (4.2%) and in 19 of these prophylaxis was discontinued. Wound haematomas developed in 25 patients (5.0%); only six required evacuation but in none of these six did deep infection occur while in hospital; in three patients, however, the wound haematoma prolonged the stay in hospital. Thus the combination of heparin and dihydroergotamine proved an effective prophylaxis against pulmonary embolism in patients undergoing total hip replacement. The risk of bleeding complications is wholly acceptable when balanced against the advantages of the therapy.

Aged↗
PubMed1984

Lipid-mediated impairment of normal energy metabolism in the isolated perfused diabetic rat heart studied by phosphorus-31 NMR and chemical extraction.

The relationship between extracellular palmitate and the accumulation of long-chain fatty-acyl coenzyme A with that of high-energy phosphate metabolism was investigated in the isolated perfused diabetic rat heart. Hearts were perfused with a glucose/albumin buffer supplemented with 0, 0.5, 1.2 or 2.0 mM palmitate. 31P-NMR was used to analyze phosphocreatine and ATP metabolism during 1 h of constant-flow recirculation perfusion. At the end of perfusion, frozen samples were taken for chemical analysis of high-energy phosphates and the free and acylated fractions of coenzyme A and carnitine. Perfusion of diabetic hearts with palmitate, unlike control hearts, caused a time-dependent and concentration-dependent reduction in ATP, despite normal and constant phosphocreatine. Concentrations of acid-soluble coenzyme A, long-chain-acyl coenzyme A and total tissue coenzyme A were elevated in palmitate-perfused diabetic hearts, while the total tissue carnitine pool was decreased. Increases in long-chain-acyl coenzyme A correlated with the reduction in myocardial ATP. This reduction in ATP could not be adequately explained by alterations in heart rate, perfusion pressure or vascular resistance.

Acyl Coenzyme A↗
PubMed1984

Salient effects of L-carnitine on adenine-nucleotide loss and coenzyme A acylation in the diabetic heart perfused with excess palmitic acid. A phosphorus-31 NMR and chemical extract study.

The beneficial effects of L-carnitine perfusion on energy metabolism and coenzyme A acylation were studied in isolated hearts from control and diabetic rats. All hearts were perfused at a constant flow rate with a glucose/albumin buffer which contained 2.0 mM palmitate. 31P-NMR was utilized to assess sequential phosphocreatine and ATP metabolism during 1 h of recirculation perfusion. L-Carnitine (5.0 mM final concentration) was added after 12 min of baseline recirculation perfusion. Frozen samples were taken after 1 h of recirculation perfusion for spectrophotometric analysis of high-energy phosphates and the free and acylated fractions of coenzyme A. L-Carnitine perfusion of diabetic hearts attenuated or prevented the reduction of ATP observed in untreated diabetic hearts. It also attenuated the accumulation of long-chain fatty-acyl coenzyme A. Although L-carnitine improved myocardial function in diabetic hearts, this was independent of any direct effect on physiological indices. Thus, the salutory effect of acute perfusion with L-carnitine on energy metabolism in the isolated perfused diabetic rat heart appears to be a direct effect on lipid metabolism.

Acyl Coenzyme A↗
PubMed1984

Quantitative analysis of quinidine analogs using ion-pairing HPLC.

Quinidine, a useful antiarrhythmic compound, is usually contaminated with dihydroquinidine, a compound that itself shows potent antiarrhythmic activity. Complete hydrogenation of quinidine followed by conversion to dihydroquinidine derivatives was explored as a basis for eliminating the analytical problems inherent in the quality control of quinidine products and for determining their pharmacological potency and pharmacokinetic parameters without interfering impurities. Attempts to resolve the quinidine analogs, dihydrocupreidine, and its benzoyloxy ester failed with normal and reversed-phase chromatography. Ion-pairing chromatography using n-octanesulfonate in methanol:water proved successful. Using 9-hydroxy-4-methoxy acridine as internal standard, separation and quantitation of the dihydroquinidine analogs from spiked plasma samples was achieved with 92 to 95% efficiency.

Chromatography, High Pressure Liquid↗
PubMed1984

Massive gastric distension in acute pancreatitis--a report of two cases.

Massive gastric distension was diagnosed in 2 patients with acute pancreatitis. Both showed signs of severe peripheral circulatory failure, and responded well to intravenous fluid replacement and nasogastric aspiration. A review of the literature revealed only 2 previously reported cases. The possible mechanisms linking the pathogenesis of these 2 conditions are discussed.

Acute Disease↗
PubMed1984

Effects of BHA, d-alpha-tocopherol and retinol acetate on TCDD-mediated changes in lipid peroxidation, glutathione peroxidase activity and survival.

Daily treatment of female rats with butylated hydroxyanisole (BHA) protected against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity. This protective effect was associated with reduced microsomal lipid peroxidation, increased glutathione peroxidase (GSH-PX) activity and decreased aryl hydrocarbon hydroxylase (AHH) activity. Retinol acetate (vitamin A) inhibited lipid peroxidation, elevated GSH-PX activity, and enhanced AHH activity. Thirty per cent of vitamin A-treated animals were alive 25 d after a lethal dose of TCDD. d-alpha-Tocopherol (vitamin E) inhibited markedly microsomal lipid peroxidation, enhanced AHH activity, and had no effect on GSH-PX activity. Only 10% of the vitamin E-treated animals were alive 25 d after a lethal dose of TCDD. The mechanism of TCDD toxicity may involve in part inhibition of GSH-PX activity with resultant lipid peroxidation by hydrogen peroxide.

Animals↗
PubMed1983

Lipid peroxidation as a possible cause of TCDD toxicity.

The target tissues of TCDD, the dysfunctions that result in death in experimental animals, and the ultimate biochemical lesion(s) caused by TCDD are not known despite numerous studies. We have shown by the thiobarbituric acid and conjugated diene methods that TCDD induces hepatic lipid peroxidation in rats. The lipid peroxidation produced by TCDD is both dose and time dependent. A 5-6 fold increase in lipid peroxidation occurs within 6 days following the administration of 40 micrograms TCDD/kg body weight/day for 3 days. Thus, the toxicity of TCDD may be caused in part by free radical-mediated lipid peroxidation that leads to general cell membrane damage which can ultimately produce death in experimental animals at acutely toxic doses.

Animals↗
PubMed1983

Abnormal phosphocreatine metabolism in perfused diabetic hearts. A 31P nuclear-magnetic-resonance study.

31P n.m.r. analysis of control and diabetic hearts perfused for 1 h with a glucose buffer showed constant and normal levels of phosphocreatine and ATP. Supplementing the buffer with 0.5, 1.2 or 2.0 mM-palmitic acid had little or no effect on high-energy-phosphate levels in control hearts. In contrast, increases in palmitate concentration produced significant decreases in ATP in diabetic hearts, despite normal and constant levels of phosphocreatine. This 31P n.m.r. study suggests a defect in phosphocreatine metabolism in the perfused diabetic heart that might be related to creatine kinase kinetics.

Adenosine Triphosphate↗
PubMed1983

In vitro screening of the effect of hydrazine derivatives on hepatic aryl hydrocarbon hydroxylase activity.

1. The effect of hydrazine derivatives on the in vitro hepatic microsomal aryl hydrocarbon hydroxylase activity was examined using Sprague-Dawley male rats. 2. All hydrazine derivatives examined have some degree of inhibition on hepatic aryl hydrocarbon hydroxylase activity. 3. The inhibitory effect is concentration dependent and is also dependent on the structural substitution of the hydrazines. The more lipophilic the derivative, the more potent the inhibition of aryl hydrocarbon hydroxylase activity.

Animals↗
PubMed1982

pKa determination of benzhydrylpiperazine antihistamines in aqueous and aqueous methanol solutions.

The pKa1 and pKa2 values of three benzhydrylpiperazine antihistamines, cyclizine (I), chlorcyclizine (II), and hydroxyzine (III), were determined at 24.5 +/- 0.5 degrees by potentiometric titration in aqueous solution to be 2.16 +/- 0.02 and 8.05 +/- 0.03, 2.12 +/- 0.04 and 7.65 +/- 0.04, and 1.96 +/- 0.05 and 7.40 +/- 0.03, respectively. The pKa2 values were also determined by titration in seven aqueous methanol solutions in the range of 11.5-52.9% (w/w) methanol. The apparent dissociation constants of I-III in the aqueous methanol solutions, psKa2, were plotted according to two linear regression equations from which the values in water, p omega Ka2, were extrapolated. The plotted variables were psKa2 versus methanol concentration (%w/w) and psKa2 + log (water concentration, M) versus 1000/epsilon, where epsilon is the dielectric constant of the aqueous methanol solution. The maximum difference between pKa2 and p omega Ka2 was observed in the case of II where p omega Ka2 was 5.23% higher. Statistical analysis of the linear regression data obtained from the plots showed that slightly better accuracy (p less than 0.13) and correlation (p less than 0.16) were obtained, but the precision was essentially equal with both methods. The observed ratio of Ka1/Ka2 in I-III, 2.75 X 10(5)-7.76 X 10(5), was attributed to solven- and space-mediated field effects and electrostatic induction between nitrogen atoms in the piperazine ring.

Chemical Phenomena↗