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Biomedical subjects

J Shepherd

Publications and source records attributed to J Shepherd.

At least 19 recordsLinked to original sources
PubMed1992

Metabolism of HDL apolipoprotein A-I and A-II in type 1 (insulin-dependent) diabetes mellitus.

Concentrations of HDL cholesterol and apolipoprotein A-I are commonly increased in Type 1 (insulin-dependent) diabetes mellitus but the mechanisms whereby diabetes influences HDL metabolism have not been studied. We investigated the metabolism of HDL apoproteins A-I and II in normolipidaemic Type 1 diabetic men (n = 17, HbA1 6.4-11.9%) without microalbuminuria but with a wide range of HDL cholesterol (0.85-2.10 mmol/l) and in nondiabetic men (n = 18) matched for body mass index and the range of HDL cholesterol. Input rates and fractional catabolic rates for apolipoproteins A-I and II were determined following injection of 125I-apolipoprotein A-I and 131I-apolipoprotein A-II tracers. Additional multicompartmental analysis was performed using a model to describe the kinetics of HDL particles containing only apolipoprotein A-I (Lp A-I) and apolipoprotein A-I and apolipoprotein A-II (Lp A-I/A-II). No gross differences from normal subjects were observed in the mean levels of lipids, lipoproteins, apoproteins and the lipolytic enzymes in the diabetic men as a result of the selection process. Furthermore, the relationship between apolipoprotein A kinetics and plasma HDL cholesterol levels appeared to be preserved in the diabetic group. However, some normal interrelationships were disrupted in the diabetic men. Firstly, the rate of apolipoprotein A-II synthesis was 22% lower than in control subjects (p less than 0.05). Modelling indicated that this was due to decreased input of Lp A-I/A-II particles whereas the input of Lp A-I particles was similar in the two groups. Secondly, there was no correlation between VLDL triglyceride and HDL cholesterol or VLDL triglyceride and the fractional catabolic rate of apolipoproteins A-I and A-II in diabetic men in contrast to that seen in control subjects. We conclude that there is a disruption in the normal association between VLDL and HDL metabolism in Type 1 diabetic men and postulate that the observed differences may be due to the therapeutic use of exogenous insulin.

Adult↗
PubMed1992

Probucol reduces plasma lipid peroxides in man.

Although primarily used as a lipid lowering drug, probucol also possesses anti-oxidant activity and has been shown in animal models to inhibit or delay the progression of atherosclerosis. It has been suggested that this anti-atherosclerotic effect may occur through inhibition of free radical oxidation of low density lipoprotein. The aim of this study was to investigate the effects of probucol on free radical activity in hyperlipidaemic patients. Plasma lipid peroxides were measured before probucol treatment, at 4 and 12 weeks treatment and then 4 weeks after stopping probucol. Lipid peroxide concentrations were significantly reduced during and 4 weeks after stopping treatment with probucol, when compared with baseline values. There were no changes in plasma vitamin E concentrations. The results of this study indicate that probucol reduces lipid peroxidation in patients, an effect which may occur through a free radical scavenging action.

Adult↗
PubMed1992

Effect of simvastatin on plasma lipid and lipoprotein concentrations and low-density lipoprotein metabolism in the nephrotic syndrome.

1. The effect of inhibiting the rate-limiting enzyme (3-hydroxy-3-methylglutaryl-CoA reductase, EC 1.1.1.88) in cholesterol synthesis on plasma lipid and lipoprotein concentrations was investigated in 16 patients with primary glomerular disease, heavy proteinuria, well-preserved renal function and hypercholesterolaemia. 2. Detailed studies of low-density lipoprotein metabolism were performed on eight patients before and after 12 weeks of simvastatin therapy. Radioiodinated tracers were used to quantify the fractional catabolic rate of low-density lipoprotein by apolipoprotein B/E receptors and alternative pathways. 3. Simvastatin produced consistent reductions in total plasma cholesterol concentration (median 36.9%), plasma low-density lipoprotein-cholesterol concentration (43.6%) and apolipoprotein B pool size (29.9%). 4. In contrast, the changes in kinetic parameters of low-density lipoprotein metabolism showed no clear pattern. Although an increase in the receptor-mediated catabolism of low-density lipoprotein was demonstrated in five patients, no change or a slight decrease was seen in three patients. Production rates were not significantly altered, although there was a slight decrease in the median value (from 12.4 to 9.7 mg day-1 kg-1). Plasma lathosterol concentration was reduced in all eight patients (range 34-71%), indirectly confirming significant inhibition of cholesterol synthesis. 5. These results suggest that, as in patients with primary moderate hyperlipidaemia, the significant cholesterol-lowering effect of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in the nephrotic syndrome is accompanied by variable changes in lipoprotein metabolism. The reasons for this heterogeneous response are unclear. This reflects our limited understanding of the metabolic basis of nephrotic hyperlipidaemia and the relationship between hepatic sterol synthesis and plasma lipoprotein kinetics.

Adult↗
PubMed1992

Post-prandial lipoprotein metabolism in nephrotic syndrome.

Post-prandial lipaemia was investigated in a group of nine subjects with nephrotic syndrome by following the concentrations of triglyceride and retinyl palmitate in the d < 1.006 g ml-1 fraction of plasma after a standard oral fat load containing vitamin A. Lipoprotein lipase and hepatic triglyceride lipase activities were measured in post-heparin plasma. Subjects with other renal disease but insignificant proteinuria acted as controls. The time course of the lipaemic response was similar in both groups although individual patients demonstrated a prolonged lipaemia. Overall, there were no significant differences in the rise in triglyceride at 6 h (nephrotic--median 2.53 mmol l-1; range 0.87-4.76 vs. control 1.88; 0.38-4.12, P = 0.34), the peak concentration of retinyl palmitate (nephrotic 0.87 mg dl-1; 0.27-2.16 vs. control 0.65; 0.24-1.89, P = 0.97) or the areas under the curve from 0-24 h for triglyceride (nephrotic 10.5 mmol. h l-1; 2.9-43.6 vs. control 9.7; 4.3-27.0, P = 1.0) or retinyl palmitate (5.5 mg.h dl-1; 1.0-23.4 vs. 4.3; 1.5-12.4, P = 0.7). At baseline, the particles in the d < 1.006 g ml-1 fraction of plasma from nephrotic subjects had a higher free cholesterol:phospholipid ratio but this difference was no longer apparent 6 h after the test meal. There were no differences in total heparin-releasable lipase, lipoprotein lipase or hepatic triglyceride lipase activities between the two groups. These data suggest that impaired clearance of chylomicrons is not a major contributor to nephrotic hyperlipidaemia in man.

Adult↗
PubMed1992

Effects of cholestyramine and acipimox on subfractions of plasma low density lipoprotein. Studies in normolipidaemic and hypercholesterolaemic subjects.

Two independent studies were designed to investigate the separate and combined effects of acipimox and cholestyramine on plasma low density lipoprotein subfractions. In the first study, normolipidaemic subjects were given cholestyramine (16 g day-1, 4 weeks), followed, after an 8-week wash-out period, by acipimox (750mg day-1, 4 weeks). In the second study, moderately hypercholesterolaemic subjects were prescribed acipimox (1250mg day-1, 10 weeks), followed by acipimox in combination with low dose cholestyramine (12g day-1) for a further 10 weeks. In the normal subjects, cholestyramine decreased total LDL mass (density (d) = 1.019-1.063g ml-1) by selectively reducing the largest, least dense LDL-I (d 1.025-1.034 g ml-1, P less than 0.05) and LDL-II (d 1.034-1.044 g ml-1, P less than 0.005) subfractions. The small, dense LDL-III (d 1.044-1060 g ml-1) showed a variable response to the resin. In the same subjects acipimox produced no overall change in total LDL mass but showed a tendency to redistribute LDL towards LDL-I (+10%) and LDL-II (+10%) in a manner related to the changes in plasma triglyceride (TG) (TG vs. LDL-III r = 0.75, P less than 0.05). In the hypercholesterolaemic subjects acipimox induced a substantial redistribution of LDL subfractions (LDL-I +84% P less than 0.05; LDL-III -50%) without affecting total LDL mass. The addition of cholestyramine produced a significant decrease in total LDL mass which was again confined to the LDL-I (-28%) and LDL-II (-23%) subfractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Plasma triglyceride and low density lipoprotein metabolism.

This study examines the relationship between plasma triglyceride and low density lipoprotein (LDL) levels by measuring the turnover of the native and 1,2 cyclohexanedione-treated lipoprotein in 25 healthy adults. Plasma triglyceride showed a strong positive correlation with circulating LDL apoprotein (apo LDL) mass. In order to achieve a satisfactory fit to the kinetic data it was necessary to postulate the existence of two plasma apo LDL pools (A and B). When subjects were grouped in quintiles on the basis of circulating apo LDL mass, pool A predominated in those in the lowest quintile. The fractional catabolic rate (FCR) of apo LDL from this pool was high (FCR = 0.57 +/- 0.06 pools day-1). As plasma triglyceride and apo LDL mass rose, apoprotein accumulated in the more slowly metabolized pool B as a result of an increase in the rate of input of apo LDL into the latter. The fractional clearance rate of protein from this pool remained unchanged at 0.26 +/- 0.04 pools day-1. Synthesis of apo LDL into pool B correlated with plasma triglyceride (r = 0.553, P less than 0.01), suggesting that the protein in this pool was derived from large, triglyceride-rich very low density lipoprotein.

Adult↗
PubMed1992

Stress management and infertility.

The author through personal experience has gained knowledge in the area of infertility and stress management. Her professional background supports the experiences, emotions and management techniques encountered with sound theoretical knowledge. This article deals with some of the procedures confronting a couple who experience infertility problems. It aims to explain and qualify common emotional responses experienced by couples and offers stress management strategies to improve their coping ability.

Female↗
PubMed1992

Plasma lipids, lipoproteins and post-heparin lipases in ponies with hyperlipaemia.

The metabolic origins of equine hyperlipaemia were investigated by analysing the concentration and composition of plasma lipoproteins in 18 ponies with the condition. The mean concentrations of cholesterol, triglyceride and very low density lipoproteins (VLDL) were increased by 4-, 52- and 19-fold, respectively, compared with a control group of 18 healthy ponies. These increases were due to the appearance of a buoyant VLDL fraction (VLDL1) not present in healthy ponies. The mean diameter of VLDL1 particles was 44% greater than control VLDL, and the particles were enriched in triglyceride and free cholesterol and depleted of cholesteryl esters, phospholipid and protein. The apolipoprotein (apo) B-100 content of VLDL1 was reduced and the ratio of apoB-100 to apoB-48 particles was 1:1, compared with 2:1 in control VLDL. The VLDL1 was also enriched in apoE, but had normal complements of apoC-II and apoC-III. The conventional VLDL (called VLDL2), LDL and HDL fractions were moderately enriched with triglyceride, and HDL contained increased amounts of apoE, apoC-II and apoC-III. The activities of lipoprotein lipase and hepatic lipase, the enzymes responsible for the catabolism of VLDL and their remnants, were increased by 2- and 3-fold, respectively, in response to the increased concentrations of their substrates. The composition of VLDL1 suggested that the liver was maximising the secretion of triglyceride by producing larger number of VLDL particles that accommodated a greater mass of triglyceride by having apoB-48 rather than apoB-100 as their structural protein. Plasma free fatty acid (FFA) concentrations were elevated in 17 of the 18 ponies, suggesting that increased FFA flux might be the stimulus for hepatic triglyceride synthesis and VLDL secretion. We conclude that overproduction, rather than defective catabolism, of VLDL was the cause of the hyperlipidaemia and that lipid lowering agents which reduce VLDL synthesis, by decreasing adipose lipolysis and FFA flux, are candidates for the management of hyperlipaemia.

Animals↗
PubMed1992

Coronary venous lipid peroxide concentrations after coronary angioplasty: correlation with biochemical and electrocardiographic evidence of myocardial ischaemia.

BACKGROUND: Raised lipid peroxide concentrations in coronary venous plasma have been reported after coronary angioplasty in humans. This may reflect increased free radical activity after myocardial ischaemia and reperfusion. If so, it may be possible to correlate lipid peroxide concentrations with the degree of myocardial ischaemia produced during angioplasty. METHODS: 15 patients (age range 42-70; 12 men) with stable angina pectoris undergoing angioplasty of a proximal left anterior descending coronary artery stenosis were studied. Plasma lipid peroxide and lactate concentrations were measured in sequential blood samples taken from the great cardiac vein before and immediately after one to five serial 60 second balloon inflations. The maximum ST segment shift during each balloon inflation was also measured. RESULTS: Lipid peroxide concentrations in coronary venous plasma were raised from pre-angioplasty values by more than 2 SDs of the relevant measurement error after 27 out of 46 (59%) balloon inflations. Lactate concentrations were raised after 43 out of 46 (93%) balloon inflations. No significant difference was found between the peak percentage change of either lipid peroxide or lactate concentrations after any of the first three serial inflations. The maximum ST segment shift after each of the first three serial inflations was also similar. Coronary venous lactate concentrations after balloon inflation correlated positively with the maximum ST segment shift, but did not correlate with lipid peroxide concentrations. CONCLUSIONS: Raised lipid peroxide concentrations in coronary venous plasma can be detected in humans after balloon angioplasty. There is no positive correlation between lipid peroxide concentrations in coronary venous plasma after angioplasty and the degree of preceding myocardial ischaemia as assessed by either ST segment shift or lactate production. These indices showed that one to three serial 60 second balloon inflations each produce a similar degree of myocardial ischaemia. The origin of the raised lipid peroxide concentrations in coronary venous plasma after angioplasty remains unknown.

Adult↗
PubMed1992

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↗
PubMed1992

Predictive testing for multiple endocrine neoplasia type 1 using DNA polymorphisms.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited predisposition to neoplastic lesions of the parathyroids, pancreas, and the pituitary. We have previously located the predisposing genetic defect to the long arm of chromosome 11 by genetic linkage. In this study, 124 members of six MEN1 families, including 59 affected individuals, were genotyped for restriction fragment length polymorphisms with different DNA probes, and the genetic linkage between these marker systems and MEN1 was determined. 13 marker systems (17 DNA probes) were found to be linked to MEN1. These markers are located within a region on chromosome 11 spanning 14% meiotic recombinations, with the MEN1 locus in the middle. Four of the marker systems are on the centromeric side of MEN1, and four on the telomeric side, based on meiotic crossovers. The remaining five DNA probes are closely linked to MEN1, with no crossovers in our set of families. The 13 marker systems can be used for an accurate and reliable premorbid test for MEN1. In most clinical situations it is possible to identify a haplotype of this part of chromosome 11 with the mutant MEN1 allele in the middle. The calculated predictive accuracy is greater than 99.5% if three such marker systems are informative. Therefore, genetic linkage testing can be used for informed genetic counseling in MEN1 families, and to avoid unnecessary biochemical screening programs.

Chromosome Mapping↗
PubMed1992

Monitoring hemangioblastoma tumor burden using plasma erythropoietin levels.

We report a 39-year-old female patient with a hepatic hemangioblastoma, polycythemia and elevated plasma erythropoietin (Epo) levels. Following orthotopic liver transplantation (OLTx), her plasma Epo levels and hematocrit normalized but began to rise several months later. This rise correlated with the appearance of multiple lung metastases. The tumor was implicated as the source of excess Epo production using Northern analysis of a resected metastatic lung nodule. Based on our results, the measurement of plasma Epo levels in patients with Epo secreting tumors could be of general utility in assessing tumor burden.

Adult↗
PubMed1992

Sister chromatid exchange (SCE) frequency in lymphocytes of patients with colorectal carcinoma treated with razoxane.

The increased risk of neoplasia following cytotoxic therapy for both malignant and nonmalignant disease is well known. Sister chromatid exchange (SCE) frequencies in patients receiving such chemotherapy are often elevated, and the persistence of high levels after treatment may provide an indicator for susceptibility to secondary neoplasia. The cytostatic drug razoxane has been used for the treatment of psoriasis, acute myeloid leukemia (AML), and colorectal carcinoma. Prolonged use of this drug, however, has been associated with the subsequent development of AML and, up to November 1987, 16 cases of acute leukemia following razoxane treatment have been reported. We report the SCE frequencies for 34 patients with colorectal carcinoma who were receiving or had previously been treated with razoxane. Our results show no significant increase in SCE levels in the razoxane group compared with either normal controls or untreated patients.

Acute Disease↗
PubMed1992

Selective measurement of lipoprotein lipase and hepatic triglyceride lipase in heparinized plasma from horses.

Affinity chromatography on heparin sepharose was used to identify 2 lipolytic enzymes in heparinized plasma from horses. One enzyme was typical of hepatic triglyceride lipase (HTGL), because it was resistant to inactivation by high concentrations of NaCl, and it did not require the addition of serum for activity. The other enzyme was identified as lipoprotein lipase (LPL), because of its inactivation at NaCl concentrations in excess of 0.2M, and its dependency on addition of serum as a source of apolipoprotein C-II activator. The enzymes were purified by 347-(HTGL) and 442- (LPL) fold, with yields of 54 and 58%, respectively. The partially purified enzymes were used to design incubation conditions that gave optimal activities for each enzyme in vitro. A selective assay was then developed for direct measurement of LPL and HTGL activities in heparinized plasma from horses. Analysis of HTGL took advantage of the almost complete inactivation of LPL when serum cofactor was excluded from the assay at the NaCl concentration that gave optimal HTGL activity. Prior incubation of heparinized plasma with sodium dodecyl sulfate to inhibit HTGL was necessary for measurement of LPL, because HTGL retained 67% of its activity at the NaCl concentration required for optimal LPL activity. Activity of each enzyme was measured in heparinized plasma from 12 Shetland ponies. The mean activity +/- SD for LPL was 3.22 +/- 1.04 mumol of fatty acids/ml of heparinized plasma/h (mumol of FA/ml/h. The mean activity for HTGL was 4.9 +/- 1.56 mumol of FA/ml/h. The performance of the assay was assessed by replicate analysis of pools of each enzyme with high and low activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Poststreptococcal glomerulonephritis: a rare complication in pregnancy.

Streptococcus pyogenes rarely causes glomerulonephritis in pregnant women. The family physician must consider this nonsuppurative cause, however, in the differential diagnosis of a pregnant patient with edema, abnormal urinalysis, and declining renal function, as this case study demonstrates.

Adult↗
PubMed1992

Lipoprotein metabolism: an overview.

The major plasma lipids, cholesterol and triglyceride, circulate in association with specific proteins as lipid-protein or lipoprotein complexes. The proteins direct and regulate the metabolism of these complexes in interacting with tissue enzymes and receptors. The metabolic fate of circulating triglyceride is governed by the activity of the enzyme lipoprotein lipase, situated in adipose tissue and skeletal muscle. Cellular demand for cholesterol, on the other hand, is met by activation of a specific receptor which mediates the delivery of sterol-rich lipoproteins to lysosomal degradation in liver and peripheral tissues. In order to prevent excess cholesterol accumulation at the periphery, there is a system of reverse cholesterol transport which involves assimilation and trapping of the sterol in the plasma lipoproteins through the action of the enzyme lecithin: cholesterol acyltransferase. Thereafter, the cholesterol is delivered to the liver, the only organ capable of excreting it in significant amounts. Disturbances in these processes may produce gross changes in the plasma lipid profile, clearly recognisable as hyperlipidaemia. However, it is becoming increasingly clear that a number of inherited traits can subtly perturb the lipoprotein spectrum and increase coronary risk even in subjects whose plasma lipoprotein profile would be considered normal.

Apolipoproteins↗
PubMed1992

Patients presenting to family physicians after a fall: a report from the Ambulatory Sentinel Practice Network.

BACKGROUND: Patients who fall present a diagnostic challenge to family physicians. The diagnostic workup of these patients must be thorough enough to detect and treat important causes of the fall yet not subject patients to unnecessary tests. Previous studies have provided only limited guidance for primary care physicians because in general they occurred in settings other than primary care and focused on a single age group. METHODS: The Ambulatory Sentinel Practice Network (ASPN) conducted a 6-month study of primary care patients of all ages presenting after a fall, or with medical problems resulting from a fall. ASPN clinicians collected information about the history, physical examination findings, and follow-up of these patients. Causes of falls were grouped into three categories: external reasons for falling, internal reasons related to gait, and internal reasons unrelated to gait. RESULTS: Participating clinicians identified 431 patients who had falls out of the 256,680 seen for any reason during the study period. The patients ranged in age from 1 to 94 years. The rate of falls for patients increased rapidly after age 65 years. Most falls occurred for reasons external to the patient, but internal reasons, both nonlocomotor and locomotor, increased after age 65 years. No nonlocomotor causes for a fall were found in patients younger than 65 years of age. Also, the rate of hospitalization of patients seen for falls was greater in the geriatric age group. CONCLUSIONS: The results highlight the need for further research about falls, particularly those occurring in pediatric and young adult patients. Furthermore, correcting environmental hazards and modifying gait problems in the elderly by increasing lower extremity and truncal strength could decrease the risk of falling.

Accidental Falls↗