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Biomedical subjects

J Shepherd

Publications and source records attributed to J Shepherd.

At least 253 records · Page 14Linked to original sources
PubMed1990

The relationship between serum cholesterol and serum thyrotropin, thyroxine and tri-iodothyronine concentrations in suspected hypothyroidism.

The relationship between serum cholesterol, thyrotropin, thyroxine and tri-iodothyronine was investigated in 1018 female patients over 40 years of age with suspected hypothyroidism. The correlation between serum thyrotropin and cholesterol (r = 0.398) and between thyroxine and cholesterol (r = -0.217) were both highly significant (P less than 0.001), but the correlation between tri-iodothyronine and cholesterol (r = -0.011) was not significant. Only in patients with a serum thyrotropin in excess of 40 mU/L was there a clinically appreciable increase in the serum cholesterol. In 139 patients treated for hypothyroidism by thyroxine replacement there was a highly significant correlation (P less than 0.001) between the decrease in serum thyrotropin and cholesterol (r = 0.593). The correlation between increase in serum thyroxine and decrease in cholesterol (r = -0.401) was also highly significant (P less than 0.001), but there was an even stronger correlation between the increase in serum tri-iodothyronine and the decrease in serum cholesterol (r = -0.529).

Aged↗
PubMed1990

Effect of insulin therapy on metabolic fate of apolipoprotein B-containing lipoproteins in NIDDM.

Non-insulin-dependent diabetic (NIDDM) subjects exhibit abnormalities in their plasma lipid and lipoprotein profiles that increase the risk of ischemic heart disease. This study was designed to examine the metabolic behavior of very-low-density (VLDL), intermediate-density (IDL), and low-density (LDL) lipoproteins in NIDDM patients before treatment and after 4 wk of insulin therapy. Basal turnover studies of 131I-labeled VLDL1 (svedberg units [Sf] 60-400) and 131I-labeled VLDL2 (Sf 20-60) apolipoprotein B (apoB) were conducted in a group of seven NIDDM patients who had been off oral therapy for 1 wk. The subjects exhibited higher than normal transport rates for VLDL1 and a diminished input of apoB into the VLDL2 density range. These observations are concordant with the hypothesis that NIDDM patients overproduce VLDL triglyceride but not apoB. VLDL1 and VLDL2 were converted to IDL and ultimately to LDL at approximately normal rates, although the delipidation pathway by which apoB-containing particles were processed exhibited different properties from that seen in control subjects. Insulin therapy reduced plasma triglyceride by 38%, and this was associated with a 41% fall in VLDL1 mass (P less than 0.01). VLDL2 was less affected (19% reduction, P less than 0.05), IDL was unchanged, and LDL fell 17% (P less than 0.05). Repeat metabolic studies revealed that the major effects of insulin were to reduce VLDL1-apoB transport (from 811 to 488 mg/day) and increase the direct input of VLDL2 into the plasma (from 182 to 533 mg/day, P less than 0.05). These alterations in VLDL production led to normalization of apoB kinetics in IDL and LDL. The fractional catabolic rate of LDL increased 19% (P less than 0.05), whereas direct input into this fraction, which had been high before treatment, was reduced. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase levels were unaffected by insulin, although the hormone did increase LPL in adipose tissue. This lack of effect on lipase activities correlated well with the observation that the rates of catabolism of apoB in VLDL1, VLDL2, and IDL were not significantly affected by insulin therapy.

Aged↗
PubMed1990

Immunological assays of apolipoproteins in plasma: methods and instrumentation.

A number of immunological techniques--radioimmunoassay, enzyme-linked immunosorbent assay (ELISA), electroimmunoassay, radial immunodiffusion, and a variety of immunoprecipitin assays--have been used to quantify apolipoproteins in plasma. This paper outlines their technical details and discusses their major advantages and drawbacks. The most sensitive procedures, RIAs and ELISAS, are best suited to quantifying those apoproteins found in low concentration in plasma. Immunoturbidimetric assays, on the other hand, which are readily automated, are being widely used to quantify apolipoproteins A-I and B. Apolipoprotein quantification is complicated by the interaction of the proteins with lipids, which can often mask their antigenic determinants. This problem may be circumvented by pretreatment of the samples, by selection of appropriate standards, or by the use of polyclonal or monoclonal antibodies that interact with permanently exposed epitopes on the lipoproteins' surfaces. Our proposed methods for measurement of the individual apolipoproteins give consideration to these approaches.

Apolipoproteins↗
PubMed1989

The Xba1 polymorphism of the apolipoprotein B gene influences the degradation of low density lipoprotein in vitro.

This study examines the influence of variation in the apolipoprotein B (apoB) gene, the major protein of low-density lipoprotein (LDL), on the LDL degradation rate in vitro. Previously we have shown (Demant et al. (1988) J. Clin. Invest. 82, 797-802) that there is an association between the fractional catabolic rate of LDL in vivo and the apoB polymorphism detected using the Xba1 restriction enzyme. Subjects with genotype X1X1 (X1 = absence of cutting site) cleared LDL more rapidly from the plasma compartment than those with the X2X2 genotype. In this study, the LDL degradation rate on dermal fibroblasts was measured for 33 individuals of genotype X1X1 or X2X2. These were subdivided into three groups: (1) young normolipidaemic, (2) older normolipidaemic and (3) older hypercholesterolaemic subjects, because age is known to markedly affect the plasma LDL concentration and may independently influence the population of LDL particles under study. In all experiments, the degradation rate of one type of LDL was compared directly in the cell culture dish with that from an individual of the alternate genotype by labelling them separately with the two iodine isotopes 125I and 131I. In the group of young normals (mean cholesterol 5.03 mmol/l, mean age 31 years), no significant difference was observed between the degradation rates of LDL derived from X1X1 individuals versus X2X2. However, in the older group of normals (mean cholesterol 5.4 mmol/l, mean age 48 years), LDL from subjects with X1X1 genotype was catabolised 17% faster than that from X2X2 subjects (P less than 0.001). A similar result was seen in hypercholesterolaemics (mean cholesterol 8.3 mmol/l, mean age 57 years) with LDL isolated from X1X1 subjects being degraded 22% more rapidly than that from X2X2 subjects. This in vitro evidence adds further weight to the hypothesis that genetic variation in the apoB gene leads to structural changes in LDL than alter its potential for degradation via the LDL receptor.

Adult↗
PubMed1989

Effect of combined therapy with bezafibrate and cholestyramine on low-density lipoprotein metabolism in type IIa hypercholesterolemia.

This study was designed to examine the influence of combined therapy with bezafibrate and cholestyramine on plasma lipids and on the metabolism of low-density lipoprotein (LDL). Twenty-one type II hyperlipidemic subjects were treated with bezafibrate alone or in combination with cholestyramine. A 17% fall in plasma cholesterol was seen with bezafibrate, and addition of cholestyramine produced an additional 9% reduction in this lipid. The effectiveness of the combination therapy was mediated through a 47% decrement in very-low-density lipoprotein (VLDL) cholesterol, a 37% reduction in LDL cholesterol, and a 15% increase in the level of that lipid in high-density lipoprotein (HDL). Plasma triglyceride fell 43% when bezafibrate was given alone, and did not change further when cholestyramine was added. The metabolism of LDL was examined in nine individuals to determine the mechanism underlying these changes. No significant modification in LDL synthetic rate was incurred with either drug regimen, whereas the fractional catabolic rate of LDL via the receptor pathway rose by 66% with bezafibrate alone and by 79% (compared to baseline) following the addition of cholestyramine. Plasma HDL rose during bezafibrate therapy due to an increase in the HDL3 subfraction. Compositional analysis of LDL showed a reduction in cholesterol ester and an increase in triglyceride and phospholipid during combined drug therapy. These results demonstrate that combined therapy with bezafibrate and cholestyramine markedly improves the lipoprotein profile in type II hyperlipidemia. The drugs appear to be complementary in their actions upon the LDL receptor pathway.

Adult↗
PubMed1989

Maintenance chemotherapy in limited small cell lung cancer: a randomised controlled clinical trial.

In a prospective randomised study 68 patients with limited small cell bronchogenic carcinoma were assigned to induction treatment with combined alternating non-cross-resistant chemotherapy plus split course radiotherapy without (NM) or with (M) subsequent maintenance therapy. Induction chemotherapy consisted of cisplatinum and VP16213q. 3 weeks followed by cyclophosphamide, vincristine and methotrexate (CVM)q. 4 weeks. Three courses of this 7-week chemotherapy programme were given. Radiotherapy to the primary lesion of 25 Gy in 13 fractions was given after each of the first and second courses of chemotherapy. Those in complete remission following the induction phase received prophylactic cranial irradiation. Those assigned to maintenance received a further six cycles of CVM after induction. The overall survival of patients randomised to maintenance therapy was significantly inferior to that of those randomised to no maintenance therapy (median survival NM 19.2 vs M 14.1 months, P = 0.05 log rank). Among patients achieving a complete remission of disease on induction therapy those receiving maintenance also showed a trend towards inferior survival (median survival NM 26.8 vs 18.0 months, P = 0.06 log rank). Deaths in each group of patients were predominantly due to tumour progression. The results do not support the use of maintenance chemotherapy after the use of intensive combined therapy induction programmes in the management of limited small cell bronchogenic carcinoma.

Adult↗
PubMed1989

Alcohol consumption among victims of violence and among comparable U.K. populations.

Controlled investigations of alcohol consumption in victims of assault are lacking. A prospective survey was performed to compare victims' drinking habits with age and sex matched U.K. populations. All 539 adult victims of assault who attended an inner-city Accident and Emergency (A and E) Department in 1986 were interviewed. Seventy-four per cent of male victims and 42% of female victims reported alcohol consumption in the 6 hours prior to assault: 30% of males and 4% of females had consumed greater than 10 units. Forty per cent males and 25% of females exceeded established safe-levels of consumption while 16% of males and 26% of females demonstrated abnormally high gamma-GT levels. Mean expenditure on alcohol by assault victims was 14% of net income, compared to 7.5% by the U.K. adult population overall. Results suggested that young male victims of assault may not be distinguishable from other young males on the basis of habitual or binge alcohol consumption. Assault victims over 25 years of age drank excessively compared to control populations and should be a priority group for alcohol education programmes.

Adolescent↗
PubMed1989

The effect of testosterone replacement on plasma lipids and apolipoproteins.

Ten men with Klinefelter's syndrome were studied to assess the effect of testosterone replacement on plasma lipids and apolipoproteins. Measurements taken before the insertion of a testosterone ester implant were compared with those obtained 1 week and 4 weeks later. Mean plasma testosterone, androstenedione, total cholesterol and calculated LDL-cholesterol increased significantly after 1 and 4 weeks. No significant changes were seen in total plasma concentrations of HDL-cholesterol, HDL-cholesterol subfractions 2 and 3 or in apoplipoproteins A-I, A-II or B. A significant correlation was seen between total cholesterol and plasma oestradiol concentrations (Rs = 0.61; P less than 0.001). A significant negative correlation was seen between the concentrations of total testosterone and total triglyceride (Rs = -0.56; P less than 0.005) but not with the other lipid parameters. Testosterone replacement is associated with slight but potentially adverse changes in plasma cholesterol levels.

Adult↗
PubMed1989

Marathon finishers and pre-race drop-outs.

The purpose of this longitudinal questionnaire study was to investigate the effects of participation or non participation in a marathon race on future running behaviour. The majority (70 per cent) of the participants who intended to run a future marathon actually did so and only 11 per cent stopped running altogether. Fewer of the pre-race drop-outs (31 per cent) who indicated their intention to run a future marathon actually did so (P less than 0.001) and more of them (24 per cent) stopped running altogether (P less than 0.001) compared with the runners in the finishers' sample. These results suggest that the experience of running in a marathon does not negatively influence future running habits. However, failure to run in a race for which an entry has been made may lead to a reduced involvement in running. The present study also examined the reasons for pre-race drop-out. Injury (36 per cent), lack of training (31 per cent) and illness (12 per cent) were the most frequently given reasons for drop-out. Few differences were found between the pre-race drop-outs and the finishers, but the drop-outs did feel that running was less important (P less than 0.001), reported a greater number of longer term injuries (P less than 0.001) and did significantly less training (P less than 0.001) than the finishers.

Adult↗
PubMed1989

Mechanism of action of bile acid sequestrants and other lipid-lowering drugs.

Although the primary and direct action of the bile acid sequestrants is to bind bile acids in the gut, their interruption of the enterohepatic recirculation of bile acids has important effects on hepatic lipoprotein metabolism. Three key enzyme systems are affected: phosphatidic acid phosphatase, cholesterol 7 alpha-hydroxylase, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. Activation of phosphatidic acid phosphatase promotes hepatic triglyceride (TG) synthesis, induces secretion of TG-rich, very low density lipoprotein particles, and consequently, increases plasma TG levels. The activation of hepatic cholesterol 7 alpha-hydroxylase promotes the conversion of intracellular cholesterol to bile acids. The decrease in intracellular cholesterol stores, in turn, increases low-density lipoprotein (LDL) receptor expression on hepatocyte surface membranes and, consequently, receptor-mediated fractional catabolism of LDL. Reduction of intracellular cholesterol may also increase the synthesis of cholesterol through activation of HMG CoA reductase. The potential loss of the sequestrant's cholesterol-lowering efficacy can be overcome by adding a drug to the regimen that inhibits HMG CoA reductase. Finally, bile acid sequestrants promote apoprotein AI synthesis by an unknown mechanism and tend to raise high-density lipoprotein (HDL) cholesterol levels, primarily by increasing plasma HDL-2 concentrations.

Anion Exchange Resins↗
PubMed1989

Recording by the police of violent offences; an Accident and Emergency Department perspective.

The British Crime Surveys have demonstrated that police-derived crime statistics are an unreliable indicator of the true number of violent offences in society. We therefore investigated police recording of consecutive victims of violence who sought treatment in a large Accident and Emergency (A & E) Department. Of victims assaulted within the boundaries of the inner-city Police Division, only one quarter were recorded by the police, though half claimed police awareness of the incident. Proportionately fewer assaults which occurred in the street, in discoteques or on Saturdays were recorded, in comparison to assaults which occurred in other locations and on other days. Proportionately more female victims were recorded, compared to males. A & E data provide a useful insight into the efficiency and effectiveness of inner-city policing. Victims Support Schemes should liaise with A & E Departments as well as with the police.

Emergency Service, Hospital↗
PubMed1989

Effects of cholesterol and lipoproteins on aldosterone secretion by bovine zona glomerulosa cells.

Freshly isolated bovine adrenocortical cells were pretreated with various concentrations of cholesterol and of high- (HDL) and low-density lipoprotein (LDL) fractions of known cholesterol content and then incubated in medium alone with and without angiotensin II. Preincubation with cholesterol (323 mumol/l) caused basal aldosterone synthesis to increase from 0.89 +/- 0.08 to 2.77 +/- 0.22 pmol/10(6) cells per hour (+/- S.E.M.) but did not significantly affect angiotensin-stimulated synthesis. Human HDL containing cholesterol at a final concentration of 129-647 mumol/l increased both basal and angiotensin-stimulated aldosterone synthesis. In HDL-treated cells, both the threshold response and responses to increasing concentrations of angiotensin were raised. Human LDL had no effect on basal or stimulated aldosterone synthesis nor did LDL alter the effects of HDL when cells were incubated with HDL and LDL in combination. Qualitatively similar results were obtained with bovine lipoproteins. These studies show that, in short-term incubations of fresh tissue, the supply of cholesterol may be a limiting factor in aldosterone synthesis and that HDL rather than LDL is the preferred source. These observations are discussed in relation first to the mechanisms by which cholesterol/HDL might augment steroid responses and secondly to other studies with cultured cells which have demonstrated a role for LDL.

Aldosterone↗