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Biomedical subjects

G H Tomkin

Publications and source records attributed to G H Tomkin.

At least 19 recordsLinked to original sources
PubMed1992

Familial cryptogenic fibrosing alveolitis: a case report.

A family of seven siblings is described, all of whom, developed finger clubbing during their third decade. Three of the seven developed cryptogenic fibrosing alveolitis (CFA). Of the remaining four siblings, two have died prematurely from conditions possibly associated with cryptogenic fibrosing alveolitis. The youngest two siblings remain asymptomatic at present. This paper reports one of the most concentrated incidences of the rare familial form of CFA.

Biopsy↗
PubMed1992

Alterations in cellular cholesterol metabolism following administration of 6-hydroxydopamine to rabbits.

1. The role of adrenergic mechanisms in the regulation of cholesterol metabolism was investigated by studying the effects of 6-hydroxydopamine (6-OHDA) on serum cholesterol levels and on the activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, acyl coenzyme A: cholesterol-O-acyl-transferase (ACAT) in the livers and intestines, and cholesterol 7 alpha-hydroxylase in the livers of male New Zealand White rabbits. 2. Total serum cholesterol levels were significantly reduced (P less than 0.01) in 6-OHDA-treated animals. This was reflected in the very low density lipoprotein, low density lipoprotein and high density lipoprotein fractions. The reduction in lipoprotein cholesterol levels reflected reduced cholesterol proportions in the lipoprotein fractions. 3. The 6-OHDA-treated animals also had significantly lower activities of intestinal (P less than 0.001) and hepatic (P less than 0.01) HMGCoA reductase. The specific activities of intestinal ACAT, hepatic ACAT and cholesterol 7 alpha-hydroxylase were comparable in both groups. 4. In contrast to the results observed in vivo, 6-OHDA did not have any in vitro effect on cholesterol biosynthesis in cultured human leucocytes. 5. This latter finding suggests that the effects of 6-OHDA on cellular cholesterol biosynthesis in vivo are indirect, possibly resulting from the known toxic effect of this drug in sympathetic nerve terminals, and imply a potential role for the sympathetic nervous system in the regulation of cellular cholesterol biosynthesis in vivo.

Animals↗
PubMed1992

An assessment of the thermogenic effects of fluoxetine in obese subjects.

Fluoxetine is an antidepressant drug with weight reducing properties. To assess whether fluoxetine has an ability to promote diet induced thermogenesis (DIT), 30 obese subjects (BMI 30-45 kg/m2) underwent a double blind, randomized, cross-over trial of 60 mg fluoxetine versus placebo. A two week single blind, run-in period on placebo was incorporated into the study to allow for placebo responders. The first stage of the study lasted for 14 days followed by a six week cross-over wash-out phase and concluded with the second 14 day stage of the study. An estimate of resting metabolic rate (RMR) was measured by continuous indirect calorimetry using the ventilated hood technique. Metabolic measurements were performed on six occasions, immediately before the first tablet was taken in the first stage, 24 hours after the first tablet was consumed and on the last day of the first stage; these three recordings were repeated on the second stage of the study. On each occasion a control reading of RMR was taken for 30 minutes then DIT was measured for 90 minutes following a lemon and glucose drink (1 g/kg body weight). Whilst a significant weight reduction (1.16 kg, P less than 0.05) occurred in the active stage, no such effect was achieved in the placebo phase. No differences were found between the two stages with regard to RMR, total DIT, peak DIT and time taken to reach peak DIT. We conclude that fluoxetine does not stimulate metabolism and that the weight reduction after 14 days therapy is due to other mechanisms.

Adult↗
PubMed1991

Hypercholesterolaemia: simvastatin and pravastatin alter cholesterol metabolism by different mechanisms.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin, reduced low-density-lipoprotein (LDL) cholesterol in hypercholesterolaemic patients by 40% (P less than 0.001). The reduction in LDL cholesterol was accompanied by a significant decrease in the esterified/free cholesterol ratio of the patients' LDL from 2.51 +/- 0.13 to 2.06 +/- 0.14 (P less than 0.01). This change led to a significant increase (P less than 0.05) in the capacity of the LDL to suppress [14C]acetate incorporation into cholesterol in mononuclear leucocytes. Furthermore, [14C]acetate incorporation into the patients mononuclear leucocytes was significantly lower (P less than 0.02) following drug treatment (117 +/- 22 vs. 162 +/- 29 nmol/mg cell protein). Comparison of simvastatin with another HMG-CoA reductase inhibitor pravastatin, showed similar reduction in LDL cholesterol. Pravastatin treatment however, did not result in a reduction in the LDL esterified/free cholesterol ratio or in the changes in cellular cholesterol synthesis and its regulation by LDL which accompanied simvastatin treatment. The activity of the enzyme acyl-coenzyme A: cholesterol acyltransferase (ACAT) in patients' mononuclear cells remained unchanged after treatment with either drug. Results of the study show that while the drugs are equally effective in lowering LDL cholesterol, simvastatin has additional compositional effects on LDL which increase its capacity to regulate mononuclear leucocyte cholesterologenesis.

Adult↗
PubMed1991

Serum lipoproteins and cholesterol metabolism in two hypercholesterolaemic rabbit models.

Serum lipoproteins and key hepatic and intestinal enzymes regulating cholesterol synthesis, esterification and catabolism, namely 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, acyl coenzyme A: cholesterol-o-acyltransferase (ACAT) and cholesterol 7 alpha-hydroxylase respectively, were compared in two hypercholesterolaemic rabbit models - the cholesterol-fed animal and the hypercholesterolaemic diabetic animal. Hypercholesterolaemia in the cholesterol-fed animals was reflected in the VLDL and LDL fractions, whereas VLDL and HDL2 cholesterol levels were elevated in the diabetic animals. The lipoproteins of the cholesterol-fed animals were enriched with cholesterol but the lipoprotein fractions in the diabetic animals were enriched with triacylglycerol. While hepatic HMGCoA reductase activity was significantly reduced in both groups, the activities of hepatic ACAT and cholesterol 7 alpha-hydroxylase were significantly increased in the cholesterol-fed animals and significantly reduced in the diabetic animals compared with controls. In the intestine, the activity of HMGCoA reductase was increased and ACAT reduced in the diabetic animals. By contrast, in the cholesterol-fed group. HMGCoA reductase activity was lower and ACAT activity was higher in comparison with the control group. These differences in lipoproteins and cellular cholesterol metabolism between the hypercholesterolaemic rabbit models may explain the differences in susceptibility to atherosclerosis, previously reported in these two animal models.

Animals↗
PubMed1991

Hypertriglyceridaemia and its influence on low density lipoprotein regulation of cellular cholesterol synthesis: a comparison between hypertriglyceridaemic diabetic and non-diabetic patients.

The present investigation was undertaken to examine the relationship between serum triglyceride and composition of lipoprotein. Six groups of patients were examined, three with Type 2 (non-insulin-dependent) diabetes and three without diabetes. The groups were further categorized on the basis of their serum cholesterol and triglyceride levels into normocholesterolaemic (serum cholesterol less than 6.5 mmol l-1) and hypercholesterolaemic (serum cholesterol greater than 6.5 mmol l-1) with and without hypertriglyceridaemia (serum triglyceride greater than or less than 3.5 mmol l-1). Low density lipoprotein (LDL) composition was determined and regulation of cholesterol synthesis by LDL was assessed by measuring its effect on [14C]-acetate incorporation into mononuclear leucocyte cholesterol. LDL from the hypercholesterolaemic diabetic patients had a significantly higher esterified cholesterol content when the patients were normotriglyceridaemic (1.14 +/- 0.04 vs 0.76 +/- 0.04 g g-1; p less than 0.01). The ability of LDL to suppress cholesterol synthesis (percent inhibition) was significantly less using LDL from the normocholesterolaemic diabetic patients or hypercholesterolaemic non-diabetic or diabetic patients compared with LDL from the normocholesterolaemic non-diabetic control subjects (47.4 +/- 3.9%, 39.1 +/- 5.1% and 35.2 +/- 4.1% vs 59.5 +/- 1.2%, p less than 0.01). However, hypertriglyceridaemia had no effect on LDL suppression of cholesterol synthesis. We conclude that hypertriglyceridaemia alters LDL composition but the alteration is not associated with the ability of LDL to regulate cholesterol synthesis.

Acetates↗
PubMed1990

Cholesterol metabolism in alloxan-induced diabetic rabbits.

The effect of diabetes control on the activities of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), cholesterol acyltransferase (ACAT), and phenol 2-monooxygenase, the major enzymes regulating cholesterol metabolism, was determined in alloxan-induced diabetic rabbits, and the results obtained were correlated with lipid and lipoprotein levels. Although intestinal HMG-CoA reductase activity was significantly increased (P less than 0.001) in poorly controlled compared with moderately controlled diabetic rabbits, there was a significant reduction in the activities of intestinal ACAT (P less than 0.01), hepatic HMG-CoA reductase (P less than 0.05) and ACAT (P less than 0.001), and phenol 2-monooxygenase (P less than 0.01). The poorly controlled animals were hypercholesterolemic (P less than 0.01), and this was reflected in the very-low-density and high-density lipoprotein fractions. Serum cholesterol levels in the nondiabetic and moderately controlled diabetic groups were similar. This increase in intestinal HMG-CoA reductase activity in the poorly controlled diabetic animals occurred in the absence of hyperphagia. Although abnormalities in cellular cholesterol metabolism could be partly responsible for the alterations in serum cholesterol levels in diabetes, the precise mechanisms underlying these enzymatic changes have yet to be elucidated.

Alloxan↗
PubMed1990

Lipoprotein composition in the alloxan-diabetic rabbit.

This study investigates the lipoprotein abnormalities in the alloxan-diabetic rabbit maintained on a standard chow diet. Poorly-controlled diabetic rabbits had elevated levels of triglyceride and phospholipid (reflected in all lipoprotein fractions) and cholesterol (reflected in the very low density and high density lipoprotein fractions) compared with well-controlled and non-diabetic rabbits. The importance of diabetic control in these changes was emphasized by the observation of a positive correlation between weight loss and serum triglyceride (rs = 0.62, p less than 0.02), cholesterol (rs = 0.65, p less than 0.01) and phospholipid (rs = 0.56, p less than 0.05). The lipoprotein fractions of the poorly-controlled rabbits were enriched with triglyceride.

Animals↗
PubMed1979

An evaluation of the bile acid binding and antacid properties of hydrotalcite in hiatus hernia and peptic ulceration.

The bile acid binding and antacid properties of hydrotalcite were studied in 25 patients with hiatus hernia or peptic ulceration. Hydrotalcite was found to have significant bile acid binding properties in the presence of free acid in the stomach. There was a definite antacid effect in both pathological entities. These results suggest that hydrotalcite may be an effective therapeutic agent in upper gastro-intestinal ulceration, warranting further investigation in lesions which are thought to involve both hydrochloric acid and bile acids in their pathogenesis.

Adult↗
PubMed1979

The dietary therapy of diabetes.

The basis of different diets for insulin dependent and maturity onset obese diabetics is discussed. The results achieved by strict calorie control in obese diabetics are compared with those in a group of patients with simple obesity and shown to be superior. The value of very low carbohydrate lager is assessed. It is concluded (a) that there is no case for severe carbohydrate restriction in diabetic diets unless there is a need for total calorie restriction and (b) 'Diet' low carbohydrate lager offers no particular advantages over ordinary lager in the diabetic diet.

Alcoholic Beverages↗
PubMed1978

Altered bile in diabetic diarrhoea.

The size and composition of the bile-salt pools in a group of diabetics with neuropathy but no diarrhoea and a group with "diabetic diarrhoea" were compared with those in a group of stable, uncomplicated diabetics. The diabetics with neuropathy had significantly more dihydroxy bile salts, a larger bile-salt pool, and a higher faecal excretion of bile than the controls. The diabetics with diarrhoea had significantly more dihydroxy bile salts, a higher glycine to taurine ratio, a smaller bile-salt pool, and increased excretions of 14C-tracer and total bile salts. We conclude that considerable alterations occur in the bile of diabetics with neuropathy or diarrhoea, and we suggest that in some cases at least these abnormalities may indicate a mechanism for diabetic diarrhoea.

Autonomic Nervous System↗