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Biomedical subjects

J Shepherd

Publications and source records attributed to J Shepherd.

At least 19 recordsLinked to original sources
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↗
PubMed1998

Outcome assessment after milieu-oriented rehabilitation: new considerations.

OBJECTIVE: This study incorporated level of functional impairment ratings at program admission into rehabilitation outcome (return to work/school) at the time of program discharge. HYPOTHESES: (1) Patients and families with better working alliance ratings will show better adjusted outcome; (2) patients seeking compensation will have poorer outcome than those not seeking compensation or receiving benefits; (3) speed of information processing and memory will relate to the level of adjusted outcome. DESIGN: Consecutive neurorehabilitation admissions from March 1992 to May 1996. SETTING: Outpatient milieu-based interdisciplinary day treatment program. SUBJECTS: Sixty-four patients with heterogeneous brain injury etiologies. MAIN OUTCOME MEASURES: Adjusted outcome, defined as level of discharge productivity adjusted by staff ratings of functional severity of impairment at program admission; work readiness and work eagerness, based on average staff ratings. RESULTS: At discharge, 89.5% of patients showed fair or good adjusted outcome; 62% were gainfully employed/full-time students; 15.6% resumed preinjury status. Better working alliance predicted better adjusted outcome. Patients seeking compensation showed significantly lower work eagerness ratings. Poorer outcome was associated with better neuropsychological status. CONCLUSIONS: Efficacy of neurorehabilitation was demonstrated for patients with better working alliance who were not seeking compensation. Adjusted outcome demonstrated greater sensitivity and utility by incorporating the variable of functional severity of impairment at program admission. Inclusion of "process" variables addressing working alliance, motivation, and capacity to work provide important contributions to understanding rehabilitation outcome.

Activities of Daily Living↗
PubMed1998

International comparison of awareness and attitudes towards coronary risk factor reduction: the HELP study. Heart European Leaders Panel.

An international survey was conducted to assess public awareness and attitudes to coronary heart disease and to establish the frequency with which certain health-related behaviours are practised in five European countries. Members of the general public (n=5013); individuals at increased risk of coronary disease (n=2500); patients who had suffered a myocardial infarction (n=1256) and members of their families (n=1249) were interviewed in a study conducted in France, Germany, Italy, Sweden and the United Kingdom. The survey revealed a considerable degree of indifference to coronary heart disease, despite the possession of a reasonable level of knowledge of the risks involved, even among patients who had suffered a myocardial infarction. At the same time, respondents declared themselves satisfied with the quality of advice about coronary health which they obtained from the medical profession and regarded these sources of information as highly credible. Individuals in five European countries therefore possess reasonable levels of knowledge about coronary heart disease. They also have access to sources of heart health information which are perceived as highly credible. Nonetheless, such information has a very limited impact on their practice of health-related behaviours.

Adult↗
PubMed1998

A tale of two trials: The West of Scotland Coronary Prevention Study and the Texas Coronary Atherosclerosis Prevention Study.

Few areas in medicine offer such an impressive portfolio of evidence of clinical benefit as does the implementation of statins in the avoidance of coronary heart disease. The West of Scotland Coronary Prevention Study and the Air Force Coronary Atherosclerosis Prevention Study together have triggered a fundamental reappraisal of the use of these agents in preventing the first heart attack. The scientific evidence in support of cholesterol lowering therapy is incontrovertible. Some questions still remain by they relate more to how treatment should be applied rather than whether it is advisable. There is no longer any controversy about the merits of lipid lowering and no justification for inertia.

Clinical Trials as Topic↗
PubMed1998

Implantable contact lens for moderate to high myopia: phase 1 FDA clinical study with 6 month follow-up.

PURPOSE: To assess the short-term safety and efficacy of the implantable contact lens (ICL) to treat moderate to high myopia. SETTING: Phase 1 U.S. Food and Drug Administration clinical study of the ICL conducted at four sites in the United States. METHODS: Ten patients with myopia of 7.00 diopters (D) or greater had implantation of a Staar Surgical ICL and were examined preoperatively (baseline) and 1 day, 1 week, and 1, 3, and 6 months postoperatively. Mean preoperative myopia was 7.75 D (range 7.25 to 9.37 D). RESULTS: Six months postoperatively, 5 of 10 eyes (50%) had an uncorrected visual acuity (UCVA) of 20/20 or better, and all eyes had a UCVA of 20/30 or better. All eyes had a best spectacle-corrected visual acuity (BSCVA) of 20/20 or better and 6 eyes (60%), of 20/15 or better. Six eyes (60%) had an improvement of one or more lines of BSCVA. Mean postoperative spherical equivalent was -0.025 D +/- 0.47 (SD). Eight eyes (80%) were within +/- 0.250 D of emmetropia, and all were within +/- 1.125 D. No intraoperative or postoperative complications or adverse reactions were observed. CONCLUSIONS: The results support the short-term safety, efficacy, and predictability of ICL implantation to treat moderate to high myopia.

Adult↗
PubMed1998

Victims of violent crime.

Violence is the leading cause of serious facial injuries in the UK. This paper outlines how and why the police and hospitals should, together, be doing more to protect the increasing numbers of victims. This paper is reproduced by kind permission of the author and the publishers of Policing Today, which is the journal of the Association of Chief Police Officers of England, Wales and Northern Ireland, Vol 3, Issue 2, June 1997. The majority of studies described in this paper were carried out by Professor Shepherd's research team at the University Hospital of Wales in Cardiff. Professor Shepherd chaired the Victim Support working party which produced the national guidelines 'Treating victims of crime', circulated in 1995 to all family doctors and A & E departments in the UK.

Crime Victims↗
PubMed1998

Associations of indices of adiposity with atherogenic lipoprotein subfractions.

OBJECTIVE: To investigate the associations of indices of adiposity with cardiovascular risk factors. SUBJECTS: 93 men and 98 women aged 18-69 y. OUTCOME MEASURES: Body mass index (BMI), waist to hip ratio (WHR), waist circumference, waist to height ratio, blood pressure, fasting concentrations of blood glucose, insulin, plasma lipids and lipoprotein subfractions, apoproteins, lipoprotein(a) and post-heparin lipases. RESULTS: BMI and waist showed similar associations (P < 0.01) with a cluster of major cardiovascular risk factors including total cholesterol, low density lipoprotein-cholesterol and very low density lipoprotein-cholesterol in men, and ratio of low density lipoprotein-/high density lipoprotein-cholesterol for both genders. Large waist circumference was significantly (P < 0.01) associated (controlled for age and smoking) with features of the metabolic syndrome, including raised insulin concentration (men: r=0.37, women: r=0.49), reduced high density lipoprotein2 (men: r=-0.30, women: r=-0.34), increased very low density lipoprotein1 mass (men: r=0.31, women: r=0.42), raised small, dense low density lipoprotein (men: r=0.30, women: r=0.31), elevated blood pressure (men: r=0.27, women: r=0.28), increased triglyceride (men: r=0.43, women: r=0.48) and apolipoprotein-B (men: r=0.32, women: r=0.35). Waist circumference also correlated with hepatic lipase/lipoprotein lipase ratio in women (r=0.52). Height adjustment did not substantially change relationships between waist circumference and risk factors. WHR correlated with fewer risk factors. CONCLUSION: For the purpose of health promotion to prevent cardiovascular disease associated with overweight and intra-abdominal fat accumulation, the general public should be advised to be aware of the risk associated with large waist circumference.

Adipose Tissue↗
PubMed1998

The effect of smoking on post-heparin lipoprotein and hepatic lipase, cholesteryl ester transfer protein and lecithin:cholesterol acyl transferase activities in human plasma.

INTRODUCTION: Smoking is associated with dyslipidaemia, particularly raised plasma triglycerides and reduced high-density lipoprotein (HDL)-cholesterol and a delayed clearance of triglyceride in fat tolerance tests. The aim of this study was to investigate whether these phenomena could be explained by a reduced lipoprotein lipase activity in smokers. METHODS: A group of 40 healthy individuals [plasma cholesterol 5.07 (SD 0.90) mmol L-1, plasma triglyceride 1.02 (SD 0.39) mmol L-1)] was studied to examine the effects of smoking on plasma enzyme activities, particularly post-heparin lipase activities. The group comprised 20 smokers and 20 non-smokers, who were matched for age, gender and body mass index (BMI). RESULTS: Post-heparin lipoprotein lipase (LPL) activity [3.89 (SD 1.58) vs. 5.85 (SD 2.30) mumol free fatty acids (FFA) mL-1 h-1, P < 0.005], but not post-heparin hepatic lipase (HL) activity, was reduced in smokers. Plasma cholesteryl ester transfer protein (CETP) activity and lecithin: cholesterol acyl transferase (LCAT) activity were measured in a subgroup of 18 individuals, comprising nine smokers with nine matched non-smokers. There was no difference in CETP activities between two groups, but smokers had a significantly reduced plasma LCAT activity [112 (SD 23) vs. 152 (SD 24) nmol cholesterol mL-1 h-1, P < 0.005]. In both smokers (r=-0.53, P < 0.05) and non-smokers (r=-0.54, P < 0.05), HDL2 concentration was negatively associated with HL activity. In non-smokers, HDL3 concentration was negatively associated with CETP activity (r= -0.77, P < 0.05), whereas in smokers HDL3 concentration was negatively associated with LCAT activity (r= -0.78, P < 0.050). CONCLUSION: It was shown by direct measurement that the activity of plasma post-heparin LPL is reduced in smokers, independently of age, gender and BMI. It is concluded that this enzyme perturbation associated with smoking may contribute to the development of the atherogenic lipoprotein phenotype seen in smokers.

Adult↗
PubMed1998

Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. London Gynaecological Oncology Group.

PURPOSE: We have examined the role of an increase in cisplatin dose-intensity in patients with advanced epithelial ovarian cancer by means of single-agent carboplatin therapy. PATIENTS AND METHODS: Two hundred twenty-seven patients were randomized to treatment and eligible for analysis. The dose of carboplatin was calculated according to the Calvert formula. One hundred seventeen patients received carboplatin at an area under the concentration time curve (AUC) of 6 for six courses, administered every 28 days, and 110 patients received carboplatin at an AUC of 12 for four courses, administered every 28 days. Patients were eligible provided they had not received prior chemotherapy or radiotherapy and had International Federation of Gynecology and Obstetrics stages II to IV or relapsed stage I epithelial ovarian cancer. RESULTS: The planned total-dose increase was 33% for the patients treated with carboplatin AUC 12, but the received percentage total-dose increase was 20%. There were no differences in progression-free or overall survival between the two treatment arms; the overall survival rate at 5 years was 31% and 34% of patients treated at AUCs 6 and 12, respectively. There was significantly more toxicity associated with carboplatin AUC 12, which resulted in more treatment delays and/or dose reductions (52% v 18%; P < .001). CONCLUSION: We have shown that carboplatin can be delivered at an AUC of 12 for four courses without granulocyte colony-stimulating factor support, although significant hematologic toxicity occurs. Nonhematologic toxicities were not clinically significant. Carboplatin offers an opportunity to intensify cisplatin therapy, but a greater than two-fold increase in dose-intensity probably needs to be achieved before significant effects on survival will be produced and hematologic support will be required.

Adult↗
PubMed1998

Effects of insulin and acipimox on VLDL1 and VLDL2 apolipoprotein B production in normal subjects.

The objective of the study was to examine the potential differential effect of insulin and acipimox (both of which reduce free fatty acid [FFA] availability) on VLDL apolipoprotein (apo) B metabolism. We studied eight healthy men (age 40 +/- 4 years, BMI 25.8 +/- 0.9 kg/m2, plasma triglycerides 1.30 +/- 0.12 mmol/l) after an overnight fast (control study, n = 8), during inhibition of lipolysis with an antilipolytic agent, acipimox (n = 8), and under 8.5-h euglycemic-hyperinsulinemic conditions (n = 5). Plasma FFAs were similarly suppressed in the acipimox and insulin studies (approximately 70% suppression). 2H3-leucine was used to trace apo B kinetics in VLDL1 and VLDL2 subclasses (Svedberg flotation rates: 60-400 and 20-60), and a non-steady-state multicompartmental model was used to derive the kinetic constants. The mean rate of VLDL1 apo B production was 708 +/- 106 mg/day at the beginning and 602 +/- 140 mg/day at the end of the control study. Production of the lipoprotein decreased to 248 +/- 93 mg/day during the insulin study (P < 0.05 vs. control study) and to 375 +/- 92 mg/day (NS) during the acipimox study. Mean VLDL2 apo B production was significantly increased during the acipimox study (399 +/- 42 vs. 236 +/- 27 mg/day, acipimox vs. control, P < 0.05) but not during the insulin study (332 +/- 51 mg/day, NS). The fractional catabolic rates of VLDL1 and VLDL2 apo B were similar in all three studies. We conclude that acute lowering of FFAs does not change the overall production rate of VLDL particles, but there is a shift toward production of smaller and denser VLDL2 particles, and, thus, the amount of total VLDL particles secreted remained constant. Insulin acutely suppresses the total production rate of VLDL apo B by decreasing the production of large triglyceride-rich VLDL1 particles. Based on these findings, we postulate that insulin has a direct suppressive effect on the production of VLDL apo B in the liver, independent of the availability of FFAs.

Adult↗
PubMed1998

Hyponatraemia associated with the use of selective serotonin re-uptake inhibitors.

OBJECTIVE: The aim of this study is to examine the frequency and severity of hyponatraemia in a psychogeriatric inpatient population taking selective serotonin re-uptake inhibitors (SSRIs). METHOD: Casenotes for 1 year were reviewed and 53 patients with 55 admissions were identified. Eighteen were treated with fluoxetine and 37 with paroxetine. Five (28%) of the patients on fluoxetine and eight (22%) on paroxetine were, or became, hyponatraemic. RESULTS: The SSRI was discontinued in two symptomatic patients. Serum sodium returned to normal in nine patients maintained on the SSRI. Two patients maintained on an SSRI remained hyponatraemic but asymptomatic. CONCLUSIONS: Hyponatraemia may be a relatively common early asymptomatic side effect of SSRIs, especially in older women. Serum sodium should be measured before commencing an SSRI and monitored during the first month. Any patient who exhibits symptoms of hyponatraemia, or whose depression apparently worsens, while on an SSRI must have their serum sodium measured. Discontinuation of the SSRI may be avoidable if serum sodium levels can be closely monitored.

Aged↗
PubMed1997

The West of Scotland coronary prevention study: economic benefit analysis of primary prevention with pravastatin.

OBJECTIVE: To estimate the economic efficiency of using pravastatin to prevent the transition from health to cardiovascular disease in men with hypercholesterolaemia. DESIGN: Economic benefit analysis based on data from the West of Scotland coronary prevention study. Treatment specific hazards of developing cardiovascular disease according to various definitions were estimated. Scottish record linkage data provided disease specific survival. Cost estimates were based on extracontractual tariffs and event specific average lengths of stay calculated from the West of Scotland coronary prevention study. SUBJECTS: Men with hypercholesterolaemia similar to the subjects in the West of Scotland coronary prevention study. MAIN OUTCOME: Cost consequences, the number of transitions from health to cardiovascular disease prevented, the number needed to start treatment, and cost per life year gained. RESULTS: If 10,000 of these men started taking pravastatin, 318 of them would not make the transition from health to cardiovascular disease (number needed to treat, 31.4), at a net discounted cost of 20m Pounds over 5 years. These benefits imply an undiscounted gain of 2,460 years of life, and thus 8121 Pounds per life year gained, or 20,375 Pounds per life year gained if benefits are discounted. Restriction to the 40% of men at highest risk reduces the number needed to treat to 22.5 (5601 Pounds per life year gained (undiscounted) and 13,995 Pounds per life year gained (discounted)). CONCLUSIONS: In subjects without evidence of prior myocardial infarction but who have hypercholesterolaemia, the use of pravastatin yields substantial health benefits at a cost that is not prohibitive overall and can be quite efficient in selected high risk subgroups.

Anticholesteremic Agents↗