Frequency of citation and outcome of cholesterol lowering trials.
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Cholesterol↗
Biomedical subjects
M F Laker
Publications and source records attributed to M F Laker.
Serum triglyceride and insulin levels are associated with erythrocyte sodium-lithium counter-transport activity in normoglycaemic individuals.
The relationship between erythrocyte sodium-lithium counter-transport activity, serum insulin, lipids and demographic factors was examined in 93 normoglycaemic predominantly normotensive individuals with mild fasting hypercholesterolaemia (greater than 5.2 mmol/l). The major significant univariate correlates of sodium-lithium counter-transport activity were fasting serum triglycerides, HDL cholesterol, the ratio of fasting glucose: insulin, apo A1, alcohol consumption and apo B. Stepwise multiple regression analysis revealed 24% of the variability in sodium-lithium counter-transport activity could be accounted for by independent contributions of fasting serum triglycerides, alcohol consumption, the fasting glucose/insulin ratio and apo A1 and ANOVA confirmed a significant relationship with fasting insulin measures that was independent of serum triglycerides (P less than 0.05). The relationship between erythrocyte sodium-lithium counter-transport activity and concentrations of serum triglycerides, HDL components, insulin and additionally alcohol consumption, could reflect the influence of those variables on erythrocyte structure and function.
Alcohol Drinking↗
A simple, sensitive technique for classification of apolipoprotein(a) isoforms by sodium dodecyl sulphate-polyacrylamide gel electrophoresis.
Lipoprotein(a) (Lp(a)) is a lipoprotein containing a unique glycoprotein, apolipoprotein(a) (apo(a)), which shows considerable heterogeneity of apparent molecular mass on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). A unifying classification of isoform has been lacking. A simple sensitive procedure for classifying apo(a) isoforms was developed in which the relative mobility of apo(a) on SDS-PAGE was related to that of apolipoprotein (apo) B-100 (Rf vs B). After Western blotting apo(a) bands were visualised by a sensitive double antibody technique employing commercial polyclonal antibodies (sheep antihuman Lp(a) antibody, alkaline phosphatase-linked donkey antisheep antibody). The technique was sensitive (lower limit of detection 0.02 micrograms apo(a)) and had good reproducibility (coefficient of variation 0.9-6.4%). Ten isoform mobilities are described (less than 0.35, 0.40, 0.50, 0.60, 0.70, 0.80, 1.0, 1.10, greater than 1.15). Individuals may have single or double band phenotypes. This classification is compatible with those previously described and the method is suitable for many laboratories, as it employs standard equipment and commercially available materials.
Apolipoproteins A↗
Microalbuminuria and associated cardiovascular risk factors in the community.
The prevalence of microalbuminuria and relationship to cardiovascular risk factors was examined in a cross-sectional community survey of cardiovascular risk factors. Microalbuminuria (when classified as albumin concentration greater than 20 micrograms/ml) was present in 6.3% of subjects but in conjunction with an albumin/creatinine ratio greater than 3.5 in only 2.2%. Diastolic blood pressure, prevalence of abnormal electrocardiographs, and to a lesser extent systolic blood pressure and fibrinogen concentration, were greater in those with albuminuria concentrations greater than 20 micrograms/ml. The strongest positive univariate correlates of albumin/creatinine ratios in those with detectable albuminuria were age, fibrinogen, blood pressure, total- and low density lipoprotein-(LDL) cholesterol, apo B and alcohol intake, whereas fasting insulin and insulin resistance were inversely correlated. Multiple regression analysis revealed that age, gender, systolic blood pressure and insulin resistance independently accounted for 37% of the variability in albumin/creatinine ratios. When those 10 subjects with microalbuminuria and albumin/creatinine ratios greater than 3.5 were matched with 20 with normoalbuminuria for age, gender and body mass index, the microalbuminuric subjects had significantly lower LDL cholesterol/apo B ratios and a tendency to lower high density lipoprotein (HDL) cholesterol and HDL cholesterol/apo A1 ratios. Microalbuminuria is uncommon in the general population, and is related to ageing, blood pressure and other vascular risk factors. It may reflect the presence of established cardiovascular disease.
Adult↗
Plasma lipids affect maximum velocity not sodium affinity of human sodium-lithium countertransport: distinction from essential hypertension.
Inheritance is a major determinant of increased sodium-lithium countertransport (SLC) activity in hypertension. However, hyperlipidaemia can also cause increased SLC activity in some individuals and it is difficult to distinguish this effect from the effect of hypertension. Erythrocyte SLC activity and its kinetic determinants sodium affinity (km) and maximum velocity (Vmax) were measured in 25 hyperlipidaemic patients and 15 normal controls (NC). Increased SLC activity (0.31 +/- SEM 0.03 mmol Li/(h x 1 cells) vs. NC 0.20 +/- 0.01, P < 0.01) in the hyperlipidaemic patients was associated with increased Vmax (0.59 +/- 0.07 vs. NC 0.41 +/- 0.03, P < 0.01) but normal km (median 120 range [40-324] mmol l-1 vs. 140 [108-260]. Lipid-lowering therapy resulted in decreased SLC activity secondary to a fall in Vmax. Km remained constant despite the changes in lipids and Vmax. The mechanism of increased SLC activity in hyperlipidaemia is different from that in essential hypertension where increased sodium affinity is found. Measurement of the kinetic characteristics of SLC may discriminate between the independent influences of hypertension and hyperlipidaemia on the sodium-lithium countertransporter.
Adult↗
Gut regulatory peptides and intestinal permeability in acute infantile gastroenteritis.
The plasma concentrations of seven gut regulatory peptides were measured in 11 infants suffering from acute gastroenteritis. Samples were taken at the time of the acute illness, upon reintroduction of feeding, and three months after recovery. These results were compared with controls. In the infants with diarrhoea, a massive increase in the fasting plasma mean (SEM) concentrations of enteroglucagon was found at the time of illness (1292 (312) v 79 (27) pmol/l), with concentrations of pancreatic glucagon, peptide tyrosine tyrosine, and motilin also being increased (17.8 (3.1) v 6.3 (1.1) pmol/l, 114.6 (15.2) v 37.0 (11.0) pmol/l, 217.6 (44.1) v 98.5 (18.3 pmol/l) respectively). The preprandial concentrations of motilin were found to be still increased at recovery (183.9 (35.4) pmol/l), but the concentrations of the other three peptides had returned to normal values. No differences in plasma concentrations of vasoactive intestinal polypeptide, neurotensin, or pancreatic polypeptide were found. An increased intestinal permeability was demonstrated at the time of diarrhoea by the urinary ratio of lactulose to mannitol, suggesting simultaneous gut damage. The effects of regulatory peptides may be relevant to the pathophysiology of gastroenteritis in infants.
Acute Disease↗
Laboratory facilities for investigating lipid disorders in the United Kingdom: results of the British Hyperlipidaemia Association survey.
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.
Apolipoproteins↗
Lipid and lipoprotein metabolism in familial combined hyperlipidaemia during treatment of sporadic phaeochromocytoma: a case study.
Lipid metabolism was evaluated during management of phaeochromocytoma in a 41 year old non-obese post-menopausal women with familial combined hyperlipidaemia. The main effect of the excess catecholamine secretion on lipid metabolism was increased lipolytic activity, lower serum triglyceride and increased HDL cholesterol concentrations, compared with findings following removal of the tumour. Before removal of the tumour, the use of beta blockers alone led to marked deterioration of the hyperlipidaemic state, and combined alpha and beta blockade additionally led to a marked reduction in fat oxidation and lipoprotein lipase activity. Overactivity of the adrenergic system leads to changes in lipid metabolism in phaeochromocytoma. Treatment of the phaeochromocytoma may lead to worsening of hyperlipidaemia pre-existing in such individuals.
Adrenal Gland Neoplasms↗
Relation between insulinemia, body mass index, and lipoprotein composition in healthy, nondiabetic men and women.
Altered lipoprotein composition may be a better predictor of cardiovascular disease than modestly increased serum lipid concentrations, although possible interactions between lipoprotein composition, obesity, and insulinemia have not been fully elucidated. Therefore, we investigated the association between different measures of insulinemia and lipoproteins in 297 healthy Caucasian men (body mass index [BMI] less than 27 in 233, greater than 27 [obese] in 64) and 295 healthy Caucasian women (BMI less than 25 in 198, greater than 25 [obese] in 97). Associations observed in both obese and nonobese men and women were between increasing tertiles of most insulin measures and serum triglyceride concentrations (p = 0.079-0.004) and the ratio of low density lipoprotein to high density lipoprotein cholesterol (p = 0.094-0.008). Graded reductions in the high density lipoprotein cholesterol to apolipoprotein A-I ratio were also recorded in obese women, with increasing tertiles of fasting (p = 0.014-0.007) and postglucose load (p = 0.001) serum insulin levels, after correcting for BMI and triglyceride concentrations. Less marked graded increases in the triglyceride to apolipoprotein B ratios were recorded in obese women with increasing tertiles of fasting (p = 0.001-0.006) and postglucose challenge (p = 0.081) insulinemic measures. In men with normal or slightly elevated cholesterol levels (fasting serum cholesterol less than 6.5 mmol/l), hyperapobetalipoproteinemia was recorded with increasing tertiles of insulinemia (p = 0.006, correcting for BMI and triglyceride concentrations), as well as in subjects with hypertriglyceridemia (fasting serum triglycerides greater than 1.70 mmol/l) (p = 0.004, correcting for BMI and age). Hyperinsulinemia and insulin resistance are associated with altered lipoprotein composition in obese women, presumably reflecting a complex interplay between sex hormones, body mass, and insulin action. Insulin resistance appears to be more associated with apolipoprotein B concentrations in men. The hyperinsulinemic nondiabetic subject may be at increased risk of cardiovascular disease because of altered concentrations of apolipoprotein concentrations and lipoprotein composition.
Adult↗
Lack of effects of hypoglycemia on glucose absorption in healthy men.
OBJECTIVE: To assess the effects of hypoglycemia on glucose absorption by examining the systemic appearance of 3-OMG (a glucose analogue that is transported by the same mechanism as glucose) after oral administration. RESEARCH DESIGN AND METHODS: Six healthy males 22-31 yr of age were studied during a hypoglycemic (50 mg [2.7 mM]/100 ml) and a euglycemic (90 mg [5.0 mM]/100 ml) glucose clamp. At 50 min after exposure to insulin, an oral glucose load containing 20 g of glucose and 4.5 g of 3-OMG dissolved in 300 ml of tap water was administered. Insulin administration was interrupted 30 min after oral glucose administration. RESULTS: Plasma glucose was clamped at 88 +/- 1.3 mg (4.9 +/- 0.1 mM)/100 ml during euglycemia and at 50 +/- 1.9 mg (2.7 +/- 0.1 mM)/100 ml during hypoglycemia. Concentrations of glucagon, growth hormone, cortisol, and epinephrine were significantly elevated during hypoglycemia. After 60 min, circulating 3-OMG concentrations increased to zeniths of 11.4 +/- 0.2 mg (585 +/- 10.0 mM)/100 ml (hypoglycemia) and 11.6 +/- 1.1 mg (585 +/- 56.0 microM)/100 ml (euglycemia; P = 0.95). Absorption of 3-OMG was evident between 15 and 20 min after administrations in both situations. Serum insulin was significantly lower during hypoglycemia compared with the control situation (345 +/- 50 microM [hypoglycemia], 445 +/- 50 microM [euglycemia], P = 0.03). CONCLUSIONS: We conclude that hypoglycemia does not seem to affect intestinal absorption of glucose as judged by systemic appearance of 3-OMG.
3-O-Methylglucose↗
Disparity between apolipoprotein E phenotypes and genotypes (as determined by polymerase chain reaction and oligonucleotide probes) in patients with non-insulin-dependent diabetes mellitus.
Apolipoprotein (apo) E phenotype and genotype frequencies, due to allelic variation at amino acids 112 and 158, have been investigated in 95 Caucasian non-insulin dependent diabetic patients (NIDDM). Phenotypes were determined by one-dimensional isoelectric focussing (IEF). In this sample, the frequency of the epsilon 2 allele was higher (0.122) and the frequency of the epsilon 4 allele lower (0.101) than previously reported in Caucasian populations (P less than 0.05). Genotypes were assigned using the technique of polymerase chain reaction and allele specific oligonucleotide probes. By contrast, the frequencies of the alleles determined by genotyping was similar to previously reported in Caucasian populations (apo epsilon 2, 0.095; epsilon 3, 0.758; epsilon 4, 0.147; P greater than 0.1). It is possible that in patients with NIDDM post-translational modification of apo E may lead to disparities, with phenotypes being unrepresentative of allelic variation at this gene locus.
Aged↗
Lipid lowering therapy leads to a reduction in sodium-lithium countertransport activity.
Erythrocyte sodium-lithium countertransport (SLC) was measured in 17 patients with either combined hyperlipidaemia or hypercholesterolaemia before and after lipid lowering therapy. Before treatment SLC related to the serum triglyceride level and was increased in combined hyperlipidaemia. After treatment the SLC had returned to normal and the change in SLC was related to the change in serum triglyceride levels. Raised SLC is associated with essential hypertension but is not related to blood pressure. Therefore, the association of raised SLC with hyperlipidaemia and essential hypertension appears to have different underlying mechanisms.
Adult↗
Plasma osmolality, iodine concentration and urographic images following high and low osmolar contrast media.
Three contrast media (sodium iothalamate, iopamidol and sodium/methylglucamine ioxaglate) in a dose of 240 mg iodine per kilogram of body weight were compared in clinical urography. The ionic monomer sodium iothalamate was the only medium to significantly elevate the plasma osmolality though it returned to normal values within 4 min. All three media exhibited first order linear kinetics. When corrected for the effects of diuresis, sodium iothalamate was shown to give the highest urinary iodine concentrations. On visual scoring sodium iothalamate produced better nephrograms and overall urograms than either of the low osmolar agents.
Contrast Media↗
Relation of lipid peroxides to macrovascular disease in type 2 diabetes.
Lipid peroxides are thought to be formed by free radicals and may play an important role in the development of atheromatous vascular disease. We have investigated the relationship between lipids, lipoproteins, coagulation factors, and lipid peroxides (measured as thiobarbituric acid reacting species (TBARS) in Type 2 diabetic patients with macrovascular disease. Eighteen diabetic and 20 non-diabetic subjects with clinical evidence of ischaemic heart disease and/or peripheral vascular disease were investigated, together with 28 healthy subjects without evidence of vascular disease. TBARS concentrations in non-diabetic (mean 5.0 (95% Cl 4.5-5.7) mumol l-1) and diabetic groups (5.6 (5.1-6.0) mumol l-1) with macrovascular disease were not significantly different although values were higher in both groups of patients with vascular disease by comparison with control subjects (2.7 (2.4-3.1) mumol l-1, p less than 0.001). Significant univariate correlations between TBARS concentrations and measures of blood glucose control (fructosamine, blood glucose and HbA1) were found for all 66 subjects (r = 0.35-0.42, p less than 0.01-p less than 0.001), although no independent association between these parameters and TBARS was demonstrated in multiple regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Transfemoral digital subtraction aortography. Are diluted high osmolar contrast media acceptable?
The ionic monomer, sodium diatrizoate at 150 mg I/ml (726 mosmol/kg) and the non-ionic monomer, iopamidol, diluted to the same iodine concentration but at 324.3 mosmol/kg, were randomly allocated to patients undergoing transfemoral intra-arterial digital subtraction angiography for lower limb peripheral vascular disease. The agents produced images of comparable quality and diagnostic efficacy. There were no significant differences between the media regarding sensations of pain and warmth. Minor neurological symptoms (headache and dizziness) occurred 7 times more frequently with the ionic monomer. There was a slight but temporary rise in plasma potassium one hour after injection of the ionic monomer but no evidence of appreciable intravascular haemolysis. The non-ionic monomer caused a slight fall in haemoglobin and haematocrit one hour after injection which is attributed to osmotic haemodilution. It is concluded that a diluted high osmolar contrast agent is an acceptable alternative to a low osmolar agent in transfemoral digital subtraction lower limb aortography.
Adult↗
Liver function tests.
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Clinical Enzyme Tests↗
Approaches to lipid and lipoprotein analysis.
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Apolipoproteins↗
Elevated sodium-lithium countertransport: a familial marker of hyperlipidaemia and hypertension?
Erythrocyte sodium-lithium countertransport was measured in normolipidaemic and hyperlipidaemic hypertensive patients, hyperlipidaemic normotensive patients and normal controls. Hypertension and hyperlipidaemia were each independently associated with raised sodium-lithium countertransport (by analysis of variance, P less than 0.01 and P less than 0.01). The effects were additive so that hyperlipidaemia could not explain raised sodium-lithium countertransport in hypertension. In hyperlipidaemic hypertensive patients, levels of plasma cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol were increased, and high-density lipoprotein (HDL) cholesterol was reduced. Of these patients, 73.3% had a known family history of hypertension. Their normotensive first degree relatives were studied, and 48% of these also had raised sodium-lithium countertransport and abnormal plasma lipids (raised cholesterol, triglycerides and LDL cholesterol, and reduced HDL cholesterol). Relatives with normal sodium-lithium countertransport had normal lipids. Therefore, raised sodium-lithium countertransport was associated with the inheritance of both hypertension and hyperlipidaemia, and this could explain why raised sodium-lithium countertransport has been associated with a family history of both hypertension and associated cardiovascular disease.
Antiporters↗