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J Shepherd

Publications and source records attributed to J Shepherd.

At least 55 records · Page 3Linked to original sources
PubMed1999

The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk.

The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomized, double-blind, placebo-controlled trial designed to test the hypothesis that treatment with pravastatin will diminish risk of subsequent major vascular events in a cohort of men and women (70 to 82 years old) with preexisting vascular disease or significant risk of developing this condition. Five thousand eight hundred four men and women in addition to receiving advice on diet and smoking, have been randomized equally to treatment with 40 mg pravastatin/day or matching placebo in 3 centers (Cork, Ireland, Glasgow, Scotland, and Leiden, The Netherlands). Following an average 3.5-year intervention period, a primary assessment will be made of the influence of this therapy on major vascular events (a combination of coronary heart disease, death, nonfatal myocardial infarction, and fatal and nonfatal stroke). A number of additional analyses will also be conducted on the individual components of the primary end point, on men, on women, and on subjects with and without previous evidence of vascular disease. Finally, an assessment will be made of the effects of treatment on cognitive function, disability, hospitalization or institutionalization, vascular mortality, and all-cause mortality.

Aged↗
PubMed1999

From best evidence to best practice - what are the obstacles?

There are numerous obstacles to overcome when implementing measures resulting from new evidence in clinical practice - some relate to practitioners in hospitals and primary care, others to patients, their relatives and public opinion. Many post-myocardial infarction (MI) patients are still discharged from hospital without any specific recommendations for risk-factor management, despite the fact that the hospital stay provides an excellent window of opportunity for treatment. Conversely, the primary-care physician may assume that as these measures were not implemented in hospital, they are unimportant. Even if recommendations for risk modification are made, the patient's attitude towards risk reduction can reduce its effectiveness. The HELP study found that the public had a reasonable knowledge of coronary heart disease (CHD) and the risks involved. However, their attitude was remarkably indifferent; even in post-MI patients, 24% were aware of lipid-lowering treatments, but did not take them, while 38% were not even aware of this form of therapy. Despite this, the medical profession was found to be the most credible source of information about CHD. Healthcare professionals, therefore, have an obligation to ensure patients receive the maximum benefit from medical advances by working together to overcome the barriers.

Coronary Disease↗
PubMed1999

Sialic acid-containing components of lipoproteins influence lipoprotein-proteoglycan interactions.

Sialic acid is a negatively charged sugar associated with the protein and lipid portions of lipoproteins. Sialic acid has been hypothesised to play an anti-atherogenic role in lipoprotein metabolism through the electrostatic inhibition of lipoprotein interactions with chondroitin-6-sulphate-rich arterial proteoglycans (APG). We conducted a series of studies using native and modified lipoproteins (VLDL1 Sf 60-400, VLDL2 Sf 20-60, IDL1 Sf 16-20, IDL2 Sf 12-16, LDL(A) Sf 8-12, and LDL(B) Sf0-8) that vary in their sialic acid content to examine the relationship between lipoprotein sialic acid content and its interaction with APG. Lipoprotein sialic acid was greatest in VLDL1 and decreased progressively with particle density until the IDL2 fraction (VLDL1 > VLDL2 > IDL1 > IDL2 = LDL(A) = LDL(B)). The pattern of reactivity of each fraction with APG was different from the pattern observed for lipoprotein sialic acid content (IDL2 > LDL(A) > LDL(B) > IDL1 > VLDL2 > VLDL1). Levels of sialic acid were lower in subjects with CHD as compared to control subjects but the presence of CHD had no effect on lipoprotein-APG complex formation when sex and plasma triglyceride levels were taken into account. There was also no significant relationship between the lipoprotein sialic acid content and the reactivity with APG within each lipoprotein fraction. Treatment of hypertriglyceridaemic subjects with ciprofibrate decreased lipoprotein-APG complex formation in all lipoprotein fractions. This was associated with a decrease in the total sialic acid content of apo B100-containing lipoproteins suggesting that the total sialic acid content of apo B100-containing lipoproteins has no influence on lipoprotein-APG complex formation. We next conducted in vitro experiments to manipulate LDL sialic acid content. Enzymatic removal of sialic acid from LDL with neuraminidase resulted in an increase in LDL-APG complex formation. This was accompanied by an increase in the exposure of free amino groups on LDL possibly due to disruption of interactions between free amino groups and sialic acid-containing components on LDL. Increasing LDL sialic acid content through incubation with ganglioside resulted in a decrease in lipoprotein-APG complex formation without any changes in the exposure of free amino groups on LDL. We conclude that total sialic acid content of lipoproteins is not a major determinant of their binding to APG. However, specific sialic acid-containing components on lipoproteins can affect their interaction with APG.

Apolipoprotein B-100↗
PubMed1999

Effect of heparin-stimulated plasma lipolytic activity on VLDL APO B subclass metabolism in normal subjects.

Heparin given intravenously enhances lipolysis, although fasting lipids are not markedly altered in long-term administration. In the present study we investigated heparin-induced acute perturbation of VLDL subclass metabolism. Eight men were examined during a control study and during an 8.5 h infusion of heparin. 2H3-leucine was used as tracer and kinetic constants derived using a non-steady-state model. Heparin infusion increased both plasma lipoprotein and hepatic lipase activity and raised plasma FFAs two-fold (P < 0.001). The fractional catabolic rate (FCR) of VLDL1 apo B increased on heparin (25.7 +/- 4.2 and 10.8 +/- 1.7 pools/d, heparin vs. control, P < 0.02). The FCR of VLDL2 apo B increased to 12.6 +/- 1.9 pools/d on heparin vs. 8.8 +/- 1.1 pools/d during the control (NS). Total VLDL apo B production was not significantly changed (824 +/- 45 and 692 +/- 91 mg/d, heparin vs. control, NS). We conclude that during heparin infusion, the catabolism of especially large triglyceride-rich VLDL1 apo B is greatly increased. However, although the FFA levels were high during the heparin study, the production of total VLDL apo B did not rise. These findings are consistent with the known action of heparin on lipoprotein lipase but indicate that acute increase in plasma FFA levels does not lead to a rise in VLDL apo B production.

Adult↗
PubMed1999

Vaginal stenosis following allogeneic bone marrow transplantation for acute myeloid leukaemia.

We report the unusual complication of vaginal stenosis occurring after allogeneic bone marrow transplantation (BMT) for leukaemia. This was in all likelihood a manifestation of chronic graft-versus-host disease (cGVHD), although the patient has no other stigmata of this and suffered little acute graft-versus-host disease (aGVHD) after BMT. Other risk factors for vaginal stenosis were considered and appear to be absent in this patient, although the total body irradiation used as part of her conditioning therapy may play a role. We suggest that vaginal stenosis may be under-reported, since female patients suffer a number of gynaecological complications after BMT, and that regular questioning and examination may aid in making an earlier diagnosis, allowing speedier instigation of therapy and thus improving quality of life.

Acute Disease↗
PubMed1999

A randomized placebo-controlled trial of fluvastatin for prevention of restenosis after successful coronary balloon angioplasty; final results of the fluvastatin angiographic restenosis (FLARE) trial.

BACKGROUND: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors competitively inhibit biosynthesis of mevalonate, a precursor of non-sterol compounds involved in cell proliferation. Experimental evidence suggests that fluvastatin may, independent of any lipid lowering action, exert a greater direct inhibitory effect on proliferating vascular myocytes than other statins. The FLARE (Fluvastatin Angioplasty Restenosis) Trial was conceived to evaluate the ability of fluvastatin 40 mg twice daily to reduce restenosis after successful coronary balloon angioplasty (PTCA). METHODS: Patients were randomized to either placebo or fluvastatin 40 mg twice daily beginning 2-4 weeks prior to planned PTCA and continuing after a successful PTCA (without the use of a stent), to follow-up angiography at 26+/-2 weeks. Clinical follow-up was completed at 40 weeks. The primary end-point was angiographic restenosis, measured by quantitative coronary angiography at a core laboratory, as the loss in minimal luminal diameter during follow-up. Clinical end-points were death, myocardial infarction, coronary artery bypass graft surgery or re-intervention, up to 40 weeks after PTCA. RESULTS: Of 1054 patients randomized, 526 were allocated to fluvastatin and 528 to placebo. Among these, 409 in the fluvastatin group and 427 in the placebo group were included in the intention-to-treat analysis, having undergone a successful PTCA after a minimum of 2 weeks of pre-treatment. At the time of PTCA, fluvastatin had reduced LDL cholesterol by 37% and this was maintained at 33% at 26 weeks. There was no difference in the primary end-point between the treatment groups (fluvastatin 0.23+/-0.49 mm vs placebo 0.23+/-0.52 mm, P=0.95) or in the angiographic restenosis rate (fluvastatin 28%, placebo 31%, chi-square P=0.42), or in the incidence of the composite clinical end-point at 40 weeks (22.4% vs 23.3%; logrank P=0.74). However, a significantly lower incidence of total death and myocardial infarction was observed in six patients (1.4%) in the fluvastatin group and 17 (4.0%) in the placebo group (log rank P=0.025). CONCLUSION: Treatment with fluvastatin 80 mg daily did not affect the process of restenosis and is therefore not indicated for this purpose. However, the observed reduction in mortality and myocardial infarction 40 weeks after PTCA in the fluvastatin treated group has not been previously reported with statin therapy. Accordingly, a priori investigation of this finding is indicated and a new clinical trial with this intention is already underway.

Angioplasty, Balloon, Coronary↗
PubMed1999

International economic analysis of primary prevention of cardiovascular disease with pravastatin in WOSCOPS. West of Scotland Coronary Prevention Study.

AIMS: The results of the West of Scotland Coronary Prevention Study (WOSCOPS) demonstrated the clinical benefit of using pravastatin for the primary prevention of cardiovascular disease in hypercholesterolaemic men. To inform decision makers, who must also consider costs, this study assesses the economic efficiency of such an intervention in a broad range of countries. METHODS AND RESULTS: A generalized model of cardiovascular disease prevention was used to estimate the cost-effectiveness of primary prevention with pravastatin compared to diet alone. This model follows a cohort of hypercholesterolaemic men over a given period quantifying the effect in terms of the avoidance of cardiovascular disease based on treatment-specific risks derived from WOSCOPS data and extensive record-linkage data on disease-specific survival. Country-specific costs are accounted for by expressing all such parameters in terms of the ratio of monthly treatment to that of managing a myocardial infarction. Over a broad range of inputs the cost-effectiveness ratios remain below $25,000 per life years gained, regardless of country. Subgroups with even better economic efficacy can be defined on the basis of higher baseline risk. CONCLUSIONS: In contrast to some previous reports, this analysis based on trial data demonstrates that pravastatin provides not only an effective means of primary cardiovascular disease prevention, but also an efficient one.

Aged↗
PubMed1999

A method in search of a theory: peer education and health promotion.

Peer education has grown in popularity and practice in recent years in the field of health promotion. However, advocates of peer education rarely make reference to theories in their rationale for particular projects. In this paper the authors review a selection of commonly cited theories, and examine to what extent they have value and relevance to peer education in health promotion. Beginning from an identification of 10 claims made for peer education, each theory is examined in terms of the scope of the theory and evidence to support it in practice. The authors conclude that, whilst most theories have something to offer towards an explanation of why peer education might be effective, most theories are limited in scope and there is little empirical evidence in health promotion practice to support them. Peer education would seem to be a method in search of a theory rather than the application of theory to practice.

Adolescent↗
PubMed1999

Lipid and lipoprotein concentrations in pregnancies complicated by intrauterine growth restriction.

Previous studies have shown that in preeclampsia, plasma lipids climb substantially above levels seen in normal pregnancies. Such lipid changes may play a role in the endothelial damage characteristic of preeclampsia. Pregnancies complicated by intrauterine growth restriction (IUGR), without preeclampsia, have similar placental pathology to preeclampsia despite the absence of the maternal systemic manifestations of hypertension and proteinuria. The aim of this study was to perform a cross-sectional study of lipid and lipoprotein concentrations in the third trimester, from normal pregnancies, and those complicated by IUGR without preeclampsia. Our hypothesis was that, in contrast to the exaggerated lipid changes seen in preeclampsia, lipid and lipoprotein concentrations in IUGR would be similar to those of matched healthy pregnant controls. Fasting blood samples for lipids and lipoprotein fractions were taken in the third trimester, from eight women with IUGR; and eight women with uncomplicated pregnancies, matched as a group for age, booking weight, parity, and gestational age at sampling. There were no significant differences (P > 0.05) in the median concentrations of triglyceride, high-density lipoprotein, and very-low-density lipoprotein 1 (VLDL1), between cases and controls. However, women with IUGR pregnancies had significantly lower cholesterol [4.95 mmol/L (3.35-7.10) vs. 7.47 (5.75-8.45); median (range) for IUGR patients and controls, respectively; P < 0.01], low-density lipoprotein (LDL)-cholesterol [2.45 mmol/L (0.95-3.60) vs. 4.25 (3.35-5.60); P < 0.01], VLDL2 mass [59.0 mg/dL (37-87) vs. 103.0 (64-168); P < 0.01], intermediate-density lipoprotein mass [56.0 mg/dL (31-110) vs. 125.6 (91-157); P < 0.01], and total LDL mass [221.0 mg/dL (104-237) vs. 380.3 (267-534); P < 0.01]. In addition, it was noteworthy that, with respect to LDL-cholesterol and total LDL mass, there was little or no overlap in the ranges of concentrations measured between cases and controls. Because VLDL2 and intermediate-density lipoprotein are the synthetic precursors to LDL in the circulation, their significantly lower median concentrations imply a failure of appropriate LDL synthesis in IUGR pregnancies. Whatever the mechanism, if our results are confirmed in larger studies and longitudinal investigations, then LDL-cholesterol measurements (when LDL-cholesterol fails to rise appropriately or is low in the third trimester) may be of use in identifying mothers with, or at risk of, a pregnancy complicated by IUGR.

Adult↗
PubMed1999

Bilateral reflex fracture of the coronoid process of the mandible. A case report.

Bilateral fractures of the coronoid process of the mandible occurred following a blow to the left temporal region in an assault. There was no evidence of direct trauma and the zygoma and other facial bones were intact. The probable cause was acute reflex contraction of the temporalis muscles leading to bilateral stress coronoid fractures. Conservative management was followed by complete resolution of symptoms.

Adult↗
PubMed1999

Apolipoprotein B overproduction by the perfused liver of the St. Thomas' mixed hyperlipidemic (SMHL) rabbit.

The St. Thomas' mixed hyperlipidemic (SMHL) rabbit (previously St. Thomas' Hospital rabbit) is a putative model of familial combined hyperlipidemia (FCH). When fed a low (0.08%) cholesterol diet, it exhibits elevations in both plasma cholesterol and triglyceride compared to New Zealand White (NZW) controls. To determine the mechanism for this hyperlipidemia we studied the secretion of apolipoprotein B (apoB)-containing lipoproteins from perfused livers of both young and mature rabbits. During a 3-h perfusion we measured the total cholesterol and triglyceride content of the medium and the cholesterol, triglyceride, and apoB content of very low density lipoprotein (VLDL)(1) (S(f) 60;-400), VLDL(2) (S(f) 20;-60), intermediate (S(f) 12;-20), and low (S(f) 0;-12) density lipoproteins (IDL, LDL). Lipoprotein concentrations increased linearly throughout the perfusion period. The rate of cholesterol output was 3-fold higher (459 vs. 137 ng/g liver/min, P = 0.003) in SMHL versus NZW rabbits whilst that of triglyceride was similar (841 vs. 662 ng/g liver/min, NS). VLDL(1) cholesterol output was elevated 2-fold (232 vs. 123 ng/g liver/min, P < 0.05) and VLDL(2) + IDL + LDL cholesterol output, 4.5-fold (106 vs. 23 ng/g liver/min, P < 0. 005) in SMHL versus NZW rabbits. ApoB output in VLDL1 was 38 ng/g liver per min in SMHL and 14 ng/g liver per min in NZW (NS). In SMHL VLDL(2) + IDL + LDL apoB was increased 9-fold at 53 versus 6 ng/g liver per min in NZW (P < 0.001). We conclude that the SMHL rabbit overproduces apoB-containing lipoproteins particularly in the VLDL(2) + IDL + LDL fraction, a characteristic consistent with its use as a model of FCH.

Animals↗
PubMed1999

A longitudinal study of the relationships between haemostatic, lipid, and oestradiol changes during normal human pregnancy.

Increased activation of both blood coagulation and fibrinolysis occurs during normal pregnancy. The responsible mechanisms are unclear, but may include increases in both oestradiol and blood lipids. We, therefore, studied the associations between fasting serum oestradiol, plasma cholesterol and triglyceride, and Factor VII activity, PAI activity, t-PA antigen, fibrin D-dimer, and vWF antigen in 10 women, each sampled on 6 occasions between 10 weeks and 35 weeks during normal pregnancy. Strong and similar individual correlations were observed between increases in FVII, PAI, t-PA and D-dimer (but not vWF) and increases in both oestradiol and triglyceride. Associations between increments in plasma cholesterol and haemostatic factors (except for FVII), were somewhat weaker. We, therefore, suggest that oestradiol-induced hypertriglyceridaemia may be a cause of elevations in plasma Factor VII activity, PAI and t-PA, and fibrin turnover (D-dimer) during normal pregnancy, but is poorly related to the increase in vWF antigen.

Adult↗
PubMed1998

Preventing coronary artery disease in the West of Scotland: implications for primary prevention.

The effectiveness of plasma cholesterol reduction therapy is no longer in question. Recent studies of cholesterol-lowering drug therapy demonstrate significant reductions in risks of mortality and coronary events in patients with existing coronary artery disease. The West of Scotland Coronary Prevention Study (WOSCOPS) demonstrated the therapy's effectiveness as primary prevention in patients without demonstrated coronary artery disease. Now that the efficacy of lipid reduction has been demonstrated conclusively, we face the difficult question of deciding what the treatment goals should be, whom to treat, and how to make those decisions cost effectively. These questions have complex social and ethical components and will lead to considerable discussion about how lipid-decreasing drugs will be used.

Anticholesteremic Agents↗
PubMed1998

Profiling risk and new therapeutic interventions: looking ahead.

The benefits of cholesterol lowering for primary and secondary prevention of coronary artery disease (CAD) have been well established. However, to accurately assess a patient's risk for CAD, clinicians must be aware of their patients' specific levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, and not just total serum cholesterol. Clinicians must also evaluate other factors in assessing a patient's risk profile. These include smoking, weight, family history of CAD, age, hypertension, and others. Absolute risk, rather than relative risk, can then be determined. Although LDL cholesterol may be the most potent predictor of risk, triglycerides are also an important indicator of CAD risk. Currently, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") are first-line therapy for the reduction of elevated levels of LDL cholesterol. All statins are effective in achieving some level of LDL cholesterol lowering. However, atorvastatin, which was recently introduced in the United States, has greater efficacy at maximal dosage in lowering LDL cholesterol, and also has a more beneficial effect on elevated levels of triglycerides, than other statins.

Anticholesteremic Agents↗