Biomedical subjects
Publications and source records attributed to G R Thompson.
Tubal pregnancy can be safely and effectively managed by MTX or CO2 laparoscopic salpingotomy techniques. Methotrexate may be superior because of its simplicity, requiring only basic laparoscopic skills, whereas laparoscopic salpingotomy necessitates operative laparoscopic input.
Soil samples were collected during certain years for the period 1982-89 from high- and low-risk areas for oesophageal cancer in Transkei, southern Africa. These samples were taken either from cultivated soils under maize monoculture, or from uncultivated soils (1989 only) adjacent to the maize fields. Analyses of mineral elements in the soil samples were performed at two independent laboratories. Furthermore, soil and maize leaf samples, from field trials in a high- and a low-risk area for oesophageal cancer were analysed. The results from this study do not agree with those reported previously for Transkei. Cultivated soils in both high- and low-risk areas were found to be highly fertile. The levels of Mn, Ni, Mg, Ca, K and soil pH were significantly higher, and Al, Fe and organic matter significantly lower in the high-risk compared with the low-risk area. Leaf analysis, although not tested statistically, indicated higher levels of Mn K, Ca and Fe, and lower levels of P, in the high-risk area.
OBJECTIVE: Adult patients with growth hormone deficiency are thought to be at higher risk of mortality from cardiovascular disease. We therefore investigated the effect of recombinant human growth hormone (rhGH) replacement therapy on fasting serum concentrations of lipids, lipoproteins and cholesterol precursors in adult growth hormone deficient patients. DESIGN: Double-blind placebo controlled trial. Patients were randomly allocated to placebo or rhGH replacement therapy (0.018 U/kg/day for 1 month followed by 0.036 U/kg/day for 1 month). PATIENTS: Eighteen patients with severe growth hormone deficiency. MEASUREMENTS: Fasting lipid, lipoprotein and cholesterol precursors (lathosterol and mevalonic acid) were measured at baseline and after 2 months. RESULTS: In the rhGH treated group there was a significant fall in serum cholesterol (P < 0.01) (6.44 +/- 0.49 to 5.71 +/- 0.48 mmol/l), LDL cholesterol (P < 0.02) (4.29 +/- 0.49 to 3.62 +/- 0.44 mmol/l), LDL cholesterol/HDL cholesterol ratio (P < 0.02) (3.99 +/- 0.62 to 3.26 +/- 0.39), apolipoprotein B (P < 0.01 (1.30 +/- 0.11 to 1.15 +/- 0.11 g/l) and mevalonic acid (P < 0.05) (13.4 +/- 10.96 to 6.21 +/- 1.91 micrograms/l). There were no significant changes in triglycerides, HDL cholesterol, apolipoprotein A1, lipoprotein (a) or lathosterol concentrations. In the GH treated group the rise in serum insulin was inversely correlated with the fall in cholesterol (P < 0.05), LDL cholesterol (P < 0.01) and apolipoprotein B (P < 0.01). There were no significant changes in any of the measured variables in the placebo group. CONCLUSION: We conclude that GH may be involved in the regulation of lipid and lipoprotein metabolism and that rhGH replacement therapy of adult GHD patients is associated with beneficial changes in lipid and lipoprotein profiles. The reduction in mevalonic acid is consistent with up-regulation of hepatic LDL receptors caused by GH and this may explain the fall in LDL cholesterol and apolipoprotein B concentrations.
In 32 women with unruptured tubal ectopic pregnancies we undertook conservative laparoscopic treatment [local injection of 20 mg methotrexate (n = 18), laser salpingotomy (n = 14)]. The results of serial quantitative beta HCG measurement were followed until either a negative level was reached or until rising levels necessitated alternative/additional therapy. Plateaued values of beta HCG were observed in both the successful (n = 16) and the unsuccessful cases (n = 5). To test the hypothesis that daily variation in the assay could account for some or all of the observed plateaued results in successful cases, the sera were retested serially on the same 'run'. In only one case did laboratory variation account for the observed plateau. The clinical implications of the findings are discussed. We conclude that serially monitored beta HCG results after conservative treatment of ectopic pregnancy may show plateaued values without indicating failure of treatment.
Explore the source record for details and available documents.
To determine the acute and long-term effects of low density lipoprotein (LDL) reduction on cholesterol biosynthesis, we studied changes in the cholesterol precursors mevalonic acid (MVA) and lathosterol in patients with heterozygous familial hypercholesterolemia undergoing LDL-apheresis. Long-term LDL-apheresis in eight patients resulted in slight but insignificant increases in plasma MVA levels and lathosterol/cholesterol (L/C) ratios over 18 months. In short-term studies, six patients not on drugs and six patients treated with lovastatin or pravastatin had blood taken immediately before and after LDL-apheresis, and afterwards on days 1, 2, 3, 5, and 7. Plasma L/C ratios and MVA concentration did not change significantly on the first day after LDL-apheresis in those not on statin therapy (1.11 +/- 0.08 vs. 1.40 +/- 0.18, and 9.2 +/- 1.3 vs. 9.1 +/- 0.6 ng/ml, respectively) but increased in the statin-treated group (from 0.78 +/- 0.09 to 1.55 +/- 0.21, P = 0.003 and from 5.0 +/- 0.7 to 11.0 +/- 1.6 ng/ml, P = 0.008, respectively). There was no clear correlation between the changes in either of these precursors and the extent of reduction of total cholesterol by LDL-apheresis, but there was a strong inverse correlation with the post-apheresis LDL-cholesterol level (r = -0.77, P = 0.002 for L/C ratio; r = -0.75, P = 0.003 for MVA). Post-apheresis changes in L/C ratio and MVA were mutually correlated (r = 0.68. P = 0.01). We conclude that LDL-apheresis stimulates cholesterol biosynthesis transiently despite concomitant therapy with an HMG-CoA reductase inhibitor, the degree of stimulation being inversely related to the level to which the LDL-cholesterol was reduced.
Explore the source record for details and available documents.
There is considerable evidence to suggest that the identification and treatment of dyslipidaemia will reduce the risk of premature CHD, i.e. before the age of 65. Diagnosis of the cause of raised plasma lipid levels will enable appropriate decisions to be taken with regard to management. The cornerstone of treatment is nutritional counselling and attention to other major risk factors for CHD, particularly smoking and hypertension. For a small percentage of patients with severe hyperlipidaemia drug therapy is indicated. Appropriate drug choices need to be made based on the particular lipid abnormality to be treated. In general those patients with clinical vascular disease are treated more aggressively than those where the aim is primary prevention. More research is needed to determine individual risk more precisely and to allow proper targeting of therapy. Genetic factors, qualitative changes in lipoproteins, lipoprotein (a), fibrinogen, and other coagulation and thrombotic factors are likely to be important in individual risk assessment. There is no doubt that more information is needed from prospective studies of lipid-lowering therapy in terms of risk benefit for affected individuals. Hopefully the major studies currently underway will fill some of the gaps in our knowledge. Until then aggressive therapy with drugs should be reserved for those at highest risk where the benefit is likely to be greatest.
Explore the source record for details and available documents.
Accelerated coronary artery disease is the most serious obstacle to long-term survival in cardiac transplant recipients. Lipid abnormalities are found frequently in these patients, and there is growing evidence that even minimally increased levels of cholesterol and triglycerides contribute to the development of accelerated coronary artery disease. However, the optimal lipid-lowering therapy after cardiac transplantation has not been defined. In an open, randomized study, the efficacy and safety of bezafibrate (400 mg/day) and fish oil (Maxepa) (10 g/day) for 3 months were compared in 87 cardiac transplant recipients with serum total cholesterol > 6.5 or triglycerides > 2.8 mmol/liter, or both. After 1 month, bezafibrate reduced total cholesterol by 13%, low-density lipoprotein cholesterol by 20% and apolipoprotein B by 13%. It also increased apolipoprotein A1 and high-density lipoprotein cholesterol by 12 and 20%, respectively, and significantly reduced fibrinogen at 3 months. Maxepa had no significant effect on these variables, but was as effective as bezafibrate in reducing triglycerides (36 and 31%, respectively). Both drugs increased lipoprotein (a) to a similar extent, and bezafibrate significantly increased serum creatinine. These results suggest that bezafibrate has better lipid-, apolipoprotein- and hemostatic modifying properties than does Maxepa, but its potentially adverse effect on renal function needs further investigation.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The clinical response to long-term reduction of the plasma LDL cholesterol concentration was studied in a man with severe coronary artery disease associated with familial defective apolipoprotein B-100 (FDB). Plasma exchange repeated at 2-week intervals, combined with lipid-lowering drugs, led to remission of angina and improved exercise test performance. A similar clinical response was achieved after LDL apheresis with dextran sulphate columns repeated once every 2 weeks in combination with drug treatment. The reduction in plasma LDL cholesterol level brought about by LDL apheresis was at least as marked in the FDB patient as in 5 patients with familial hypercholesterolaemia. We conclude that FDB patients with coronary artery disease may derive clinical benefit from prolonged reduction of their plasma cholesterol levels and that LDL containing apo B-100 in which arginine at position 3500 is replaced by glutamine is removed from plasma by dextran sulphate columns as efficiently as is normal LDL.
A patient presented with apparent septicaemic shock. Full invasive cardiovascular monitoring revealed systemic hypotension, high normal cardiac output, and a low systemic vascular resistance. Maintenance of systemic vascular resistance and blood pressure was shown to be highly dependent on noradrenaline. Subsequent investigation revealed the presence of a phaeochromocytoma producing adrenaline. The mechanisms by which phaeochromocytomas may produce hypotension are discussed.
AIMS: To determine the availability of facilities for the investigation of hyperlipidaemia in the United Kingdom. METHODS: A questionnaire was sent to all health districts in the United Kingdom. RESULTS: The response rate was 81%. All laboratories used enzymatic techniques to measure serum triglyceride and cholesterol concentrations, although there were differences in standardisation procedures. Reference ranges for serum lipids were quoted by 58% of laboratories while 50% quoted "desirable limits". Almost half specified that fasting blood samples were required. High density lipoprotein cholesterol concentrations were estimated by 75% and apolipoproteins AI and B by 14% of laboratories; there were differences in specimen type and considerable diversity in procedures used for measurement. CONCLUSIONS: Many laboratories were unaware of current recommendations for screening for hypercholesterolaemia in the community. The present survey indicated an urgent need for the introduction of better reference methods, standardisation, and quality assurance procedures before apolipoproteins become a routine part of coronary heart disease risk assessment.
A sample of 200 patients with a clinical diagnosis of heterozygous (189) or homozygous (11) familial hypercholesterolemia (FH) attending lipid clinics in the London area have been screened for the presence of major gene defects in the low density lipoprotein (LDL) receptor gene by Southern blotting of genomic DNA with specific probes. This study is part of a project to determine the frequency of known mutations in the LDL receptor gene in this population. A new polymorphism for the enzyme Bgl II was identified by hybridization with a probe specific for the promoter plus exon 1 of the LDL receptor gene. The observed frequency of the rare allele, characterized by a Bgl II fragment of 13 kb compared with 10 kb for the common allele, was 0.08 in this group of FH patients. Several individuals who were heterozygous for the rare allele were also heterozygous for a mutation elsewhere in the LDL receptor gene that is known to cause FH. Eight different mutations, seven deletions and one duplication, were detected in a total of nine patients, accounting for 4.5% of the mutant alleles in this group. Three of the mutations are apparently identical to deletions that have been described previously in FH patients of British or European origin, while the remaining five have not been described. Two of these were in patients of Polish and Asian Indian origin, while the other three were in patients of apparently British ancestry.
Ortho,para,dichlorodiphenyl dichloroethane (o,p'DDD, Mitotane (Roussell)) is used as an adrenolytic drug to reduce adrenocortical mass and circulating cortisol levels in Cushing's syndrome but has the unwanted side-effect of inducing hypercholesterolaemia. This paper examined the mechanism of that effect in 30 patients with Cushing's syndrome treated with o,p'DDD during the past 10 years. o,p'DDD increased serum cholesterol by 68 per cent, mainly by increasing LDL-cholesterol. The latter effect was not due to impaired binding of LDL to its receptor, as shown in vitro using cultured fibroblasts. Increases in plasma mevalonic acid during o,p'DDD administration were suggestive of increased cholesterol synthesis, this effect being reversed by simvastatin. These findings suggest that o,p'DDD causes hypercholesterolaemia by increasing cholesterol synthesis. It is proposed that this effect is due to the drug's known ability to block cytochrome P450-mediated reactions, thus impairing the formation of oxysterols responsible for down-regulating hepatic cholesterol synthesis. Treatment with simvastatin, an inhibitor of cholesterol synthesis, reverses the hyperlipidaemia and enables o,p'DDD therapy to be maintained without increasing cardiovascular risk.