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Biomedical subjects

R Wright

Publications and source records attributed to R Wright.

At least 127 records · Page 7Linked to original sources
PubMed1986

Depressed selenium and vitamin E levels in an alcoholic population. Possible relationship to hepatic injury through increased lipid peroxidation.

Serum selenium and vitamin E levels have been measured in subjects with established alcoholic liver disease, in alcoholics within the community, and in appropriate controls. Both serum selenium and vitamin E levels were shown to be significantly depressed (P less than 0.01) in the alcoholic study groups and serum selenium was more markedly depressed in subjects with established liver disease (controls, serum selenium 108 +/- 13 micrograms/liter, vitamin E 27.6 +/- 7.2 mumol/liter; community alcoholics, serum selenium 94 +/- 19 micrograms/liter, vitamin E 15.3 +/- 3.4 mumol/liter; alcoholic liver disease, serum selenium 78 +/- 15 micrograms/liter, vitamin E 14.7 +/- 5.6 mumol/liter). Depressed serum selenium levels correlated closely with poor nutritional status (r = 0.91). There were no changes in serum glutathione peroxidase activity. Liver disease activity, as judged by transaminase (AST), was more markedly abnormal in subjects with combined vitamin E and selenium deficiency compared to those with normal levels or isolated deficiencies (no deficiency, AST 48 +/- 19 units, combined deficiency, AST 75 +/- 21 units, P less than 0.03). Serum lipid peroxides were elevated in those with combined deficiency and the values correlated significantly with serum transaminases (r = 0.40, P = 0.03).

Adult↗
PubMed1986

Corynebacterium parvum-elicited hepatic macrophages demonstrate enhanced respiratory burst activity compared with resident Kupffer cells in the rat.

We have recently demonstrated that release of oxygen-derived free radicals by activated hepatic macrophages may be involved in the pathogenesis of a rat model of liver injury induced by Corynebacterium parvum and endotoxin. In the present study we have compared the respiratory burst activity of isolated normal rat Kupffer cells with that of hepatic macrophages elicited by C. parvum. Superoxide production (O2-.) and glucose oxidation via the hexose monophosphate shunt (HMPS) were low in normal Kupffer cells, but were significantly increased (O2-. 2.1-fold, HMPS 1.7-fold) by phorbol myristate acetate, a stimulant of the respiratory burst. Corynebacterium parvum-elicited hepatic macrophages demonstrated significantly enhanced superoxide production and HMPS activity compared with normal Kupffer cells, both in the absence of specific stimuli (O2-. 3.3-fold, HMPS 5.3-fold) and after exposure to phorbol myristate acetate (O2-. 4.5-fold, HMPS 5.3-fold). These results demonstrate that normal Kupffer cells are capable of exhibiting respiratory burst activity, but this is markedly increased for hepatic macrophages elicited by an inflammatory stimulus.

Animals↗
PubMed1986

Hepatic regeneration and metabolism after partial hepatectomy in normal rats: effects of insulin therapy.

The effect of insulin therapy on liver regeneration has been studied in normal fed rats 12, 24 and 48 h after partial hepatectomy. Dry weight of regenerating liver increased between 12 and 48 h after partial hepatectomy and was unaffected by insulin therapy. [6-3H] Thymidine uptake peaked at 24-h (24.7 +/- 2.4% of total liver cells) and insulin treatment had no additional effect. At 12-h after partial hepatectomy, hepatic [ATP] was decreased 15%, while [ADP] and [AMP] were increased 47% and 83% respectively compared with sham-operated animals. Partial hepatectomy also caused an increase in hepatic [triglyceride], a decrease in hepatic [glycogen] and an increase in the levels of glucose and several glycolytic intermediates. The hepatic redox ratios, [lactate]:[pyruvate] and [3-hydroxybutyrate]:[acetoacetate], were elevated. Insulin therapy had only minor effects on hepatic adenine nucleotide levels, intermediary metabolite concentrations or intrahepatic redox ratios after partial hepatectomy. These findings suggest a decreased hepatic intracellular energy state in regenerating liver; insulin therapy in normal rats does not influence this metabolic change nor the regenerative response.

Adenine Nucleotides↗
PubMed1986

Hepatic regeneration and metabolism after partial hepatectomy in diabetic rats: effects of insulin therapy.

The effect of insulin deficiency on liver regeneration has been assessed in untreated v. insulin-treated streptozotocin (65 mg kg-1) diabetic rats, 12, 24 and 48 h after partial hepatectomy. Dry weight of regenerating liver increased from 12 to 48 h after partial hepatectomy and insulin treatment caused a further minor increase at 24 h. [6-3H]Thymidine uptake in untreated rats peaked at 24 h (12.5 +/- 3.4% of total cells labelled). Insulin therapy produced a delayed 168% rise in uptake at 48 h. Insulin deficiency alone in sham-operated animals caused a 33% decrease in hepatic [ATP], while [ADP] rose by 43% and [AMP] by 86% at 12 h. Partial hepatectomy produced only minor further abnormalities in untreated animals. Insulin therapy increased hepatic [ATP] and decreased [ADP] and [AMP] 12 h after partial hepatectomy, but [ATP] remained decreased (15%) and [ADP] and [AMP] increased (45% and 73% respectively) compared with insulin-treated sham-operated controls. Metabolite changes observed after partial hepatectomy in untreated animals, including a decrease in hepatic [glycogen] and increases in [triglyceride] and the ratios of [lactate]:[pyruvate] and [3-hydroxybutyrate]:[acetoacetate], were partially reversed by insulin treatment. Insulin deficiency thus impairs regeneration after partial hepatectomy and magnifies the decline in hepatic intracellular energy state and the metabolite changes associated with liver regrowth.

Adenine Nucleotides↗
PubMed1985

Mortality of hepatitis B positive blood donors in England and Wales.

Of 2880 men and 1054 women who were found to be hepatitis B surface antigen positive by the Blood Transfusion Service in England and Wales between 1971 and 1981, more than 92% were traced to the end of 1983. 5 deaths from hepatocellular carcinoma had been reported in men, giving a relative risk compared with the male population of England and Wales as a whole of 42. There had been no deaths from liver cancer in women. In both men and women there was a greater than ten-fold increase in the risk of death from chronic liver disease. Secondary preventive action may be indicated.

Adult↗
PubMed1985

Oxygen-derived free radicals promote hepatic injury in the rat.

We have investigated the possible protective effect of superoxide dismutase and allopurinol in a rat model of mild and severe hepatic necrosis produced by Corynebacterium parvum with or without endotoxin. Histology showed a sinusoidal mononuclear cell infiltrate with multiple granulomata but variable degrees of hepatic necrosis. In the severe hepatic injury model there was a reduction in mortality, associated with a decrease in histologic and biochemical evidence of hepatic necrosis, after treatment with superoxide dismutase. This protective effect was not demonstrated with partially heat-inactivated superoxide dismutase. In the mild hepatic injury model similar trends in reduction of serum levels of hepatic enzymes were observed after treatment with both superoxide dismutase and allopurinol. These results indicate that oxygen-derived free radicals may play an important role in the pathogenesis of hepatic injury in the rat.

Alanine Transaminase↗
PubMed1985

Failure of sulfites to produce clinical responses in patients with systemic mastocytosis or recurrent anaphylaxis: results of a single-blind study.

Although sulfite sensitivity can precipitate asthma in a subpopulation of subjects with asthma, its role in precipitating anaphylaxis or as a nonspecific mast cell degranulator in systemic mastocytosis has not been examined. To evaluate critically the importance of sulfites in these diseases, eight patients with systemic mastocytosis and 25 patients with unexplained, recurrent anaphylaxis were challenged in a single-blind fashion; sodium bisulfite in capsules was administered in increasing doses of 1, 5, 10, 25, 50, 100, and 200 mg every 30 minutes. On separate occasions a liquid suspension of 200 mg of sodium bisulfite was administered to one patient with systemic mastocytosis and nine patients with anaphylaxis. Vital signs, pulmonary function tests, plasma histamine levels, and clinical reactions were monitored. There were no observable responses in either the mastocytosis group or in 23 of 25 patients in the anaphylaxis group. Two patients in the anaphylaxis group with initial positive challenges had similar symptoms on subsequent placebo challenge. One subject with asthma and with a history suggestive of sulfite sensitivity responded to oral challenge with 5 mg of sodium bisulfite and 100 micrograms of sodium bisulfite intradermally with a dramatic reduction in FEV, requiring treatment with bronchodilators. A comparison of baseline plasma histamine levels with those obtained after the sulfite challenge procedure in each category demonstrated a significant rise (p less than 0.05) in the systemic mastocytosis group. The overall level of significance determined by applying paired sample t tests to the histamine data from all subjects was p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1985

Loneliness among the elderly: a causal approach.

The purpose of this study was to develop and assess a causal model of loneliness among a national probability sample of noninstitutionalized elderly adults. Path analysis was used to test the causal model. The findings indicated that marital status, self-perceived health status, income, social activity levels, and a sense of social fulfillment directly predict feelings of loneliness. The social fulfillment variable, however, was the most important predictor. An interesting finding was that age had no notable direct or indirect effect on feelings of loneliness.

Age Factors↗
PubMed1985

Drug influences on rat hepatic macrophage enzyme production and release in vitro.

Drug influences on hepatic macrophage enzyme release have been investigated using a rat model of macrophage recruitment and activation. N-acetyl-glucosaminidase (NAG), a lysosomal enzyme, and plasminogen activator (PA), a cytosolic enzyme, have been measured in both cell lysates and supernatants after 24 h in culture. 6-mercaptopurine (6-MP) and azathioprine significantly decreased (P less than 0.03) the enhanced production of NAG by recruited macrophages following stimulation in vitro (total NAG activity, nmol substrate hydrolysed/microgram cell protein; recruited macrophages exposed to endotoxin, no drug exposure 0.63 +/- 0.08, azathioprine 0.44 +/- 0.08, 6MP 0.36 +/- 0.06). Prednisolone, azathioprine and 6MP significantly reduced (P less than 0.05) the supernatant release of PA in response to endotoxin exposure in vitro by both cell types (supernatant PA values after 24 h in culture, recruited macrophages exposed to endotoxin, no drug 26.0 +/- 2.9 units, prednisolone 18.5 +/- 1.7 units, levamisole 27.3 +/- 4.7 units, azathioprine 18.1 +/- 2.3 units, 6MP 17.3 +/- 1.5 units). The results from this study indicate that certain drugs used in human liver disease are able to modify the secretory activity of rat hepatic macrophages.

Acetylglucosaminidase↗
PubMed1985

Pharmacology of propranolol in patients with cirrhosis and portal hypertension.

Ten patients with cirrhosis and protal hypertension received an initial 20 mg oral test dose of propranolol and subsequently 160 mg of a slow release preparation, orally, each day for seven days. Protein binding, serial plasma propranolol concentrations and effects on heart rate were studied. Protein binding was slightly reduced (mean 85%, range 78.9-88.1%) compared with four normals (mean 87.9%). In patients with severe liver disease (serum albumin less than 30 g/l) propranolol remained detectable in plasma 24 hours after the single 20 mg dose and high steady state concentrations (mean 266.5 ng/ml, range 84-406) were observed during regular dosing. At steady state there was a significant correlation between log total plasma propranolol concentrations and the percentage fall in heart rate (r = 0.659, p less than 0.05). We suggest that in patients with severe liver chronic disease (serum albumin less than 30 g/l), propranolol therapy should be initiated in hospital. The starting dose should be low (20 mg of the conventional formulation tds or 80 mg of the slow release preparation daily) and that regular monitoring of the heart rate should be carried out.

Aged↗
PubMed1985

The effect of omeprazole on insulin induced gastric secretion in man.

The effect of oral omeprazole on insulin induced gastric secretion was studied in 12 healthy subjects. Each subject participated in two secretory tests receiving an intravenous infusion of insulin (0.03 units/kg/h) and being randomly allocated to receive 30mg or 60mg omeprazole suspended in 100ml water containing 16 mmol NaHCO3 on the second study day. Peak plasma concentrations of omeprazole were achieved within 30 minutes of administration in all but one subject and plasma half life was 30 minutes. Mean peak stimulated acid output in the six subjects receiving 30mg omeprazole was reduced to 4.3 +/- S.E. 1.8 mmol/h from a control value of 16.8 +/- 2.2 mmol/h (p less than 0.05) and in six subjects receiving 60mg omeprazole, mean peak output fell to 3.4 +/- 2.1 mmol/h from a control value of 12.3 +/- 2.6 mmol/h (p less than 0.05). The two doses of omeprazole produced similar reduction in acid secretion (74% and 73% respectively) but neither dose affected pepsin secretion. Both doses of omeprazole were associated with a small statistically insignificant increase in the plasma gastrin response to insulin infusion.

Adult↗
PubMed1985

Efficacy of crystalloid cardioplegic solutions in patients undergoing myocardial revascularization. Effect of infusion route and regional wall motion on preservation of adenine nucleotide stores.

The effect of varying the mode of cardioplegic delivery and the presence of regional wall motion abnormalities on myocardial protection by crystalloid cardioplegic solutions was assessed in 68 patients undergoing coronary artery bypass grafting. Serial transmural biopsy specimens from the left ventricular apex were assayed for adenosine triphosphate. All patients had more than 75% stenosis of the left anterior descending coronary artery. They were prospectively randomized into Groups I and II to receive (I) all cardioplegic solution infused via the aortic root or (II) reinfusions of cardioplegic solution given both centrally and through the completed distal left anterior descending anastomosis. Patients were also stratified as to the presence of normal (N) or impaired (Ab) apicoanterior regional wall motion. Inadequate delivery of cardioplegia during ischemia in Group I was manifested by a 41% (p less than 0.01) depletion of adenosine triphosphate stores in abnormally contracting myocardium distal to the left anterior descending stenosis that was not repleted after restoration of coronary flow and a 27% (p less than 0.05) decline in ATP stores during reperfusion in myocardium with normal preoperative wall motion. In contrast, nucleotide stores were preserved at preischemic levels throughout ischemia and reperfusion in Group II regardless of preoperative wall motion. Preservation of ATP did not correlate with duration of ischemia, highest recorded septal temperature, or volume of cardioplegic solution infused. Two patients in each group had a new perioperative infarction. However, 38% of patients in Group IAb required transient inotropic support versus 5% in Group IIAb (p less than 0.05). These data emphasize that reinfusion of cardioplegic solutions distal to coronary obstructions is mandatory for optimal myocardial protection during coronary revascularization.

Adenosine Triphosphate↗