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Biomedical subjects

J Shepherd

Publications and source records attributed to J Shepherd.

At least 163 records · Page 9Linked to original sources
PubMed1995

Public health aspects of third molar surgery. The effect of surgeons' treatment thresholds on efficiency and effectiveness.

Disease associated with third molars is being recognised increasingly as a public health problem in terms both of rising incidence and of appropriate use of resources. Since minor alterations in treatment philosophy can have a substantial impact on the efficiency and effectiveness of oral surgery services, this study examines the sensitivity and specificity of oral surgeons' decisions and uses Receiver Operator Characteristics (ROC) analysis to investigate their ability to detect and make appropriate judgements about teeth which need extraction according to established criteria. The study shows that the seniority of the surgeon making the treatment decisions had no significant effect on the decisions made and also demonstrated wide variations between the treatment plans made by individual clinicians. It is clear from this study that if an efficient and effective service for the treatment of third molar disease is to be commissioned, policy decisions about criteria for intervention must be made by health service purchasing authorities, adhered to by secondary care providers, and shared with the primary care practitioners who refer patients for treatment.

Decision Making↗
PubMed1995

Overproduction of small very low density lipoproteins (Sf 20-60) in moderate hypercholesterolemia: relationships between apolipoprotein B kinetics and plasma lipoproteins.

An analysis of apolipoprotein (apo) B turnovers conducted in subjects with moderate hypercholesterolemia was performed to discover relationships that may exist between apoB kinetic parameters and plasma lipid and lipoprotein levels. A group of 21 subjects with plasma cholesterol in the range 250-300 mg/dl and triglyceride < 265 mg/dl were injected with tracers of 131I-labeled very low density lipoprotein 1 (VLDL1, Sf 60-400) and 125I-labeled VLDL2 (Sf 20-60) prepared by cumulative flotation ultracentrifugation. The metabolism of apoB in these fractions was followed through intermediate density (IDL, Sf 12-20) to low density (LDL, Sf 0-12) lipoprotein. The most consistent feature giving rise to the higher apoB levels that occurred in VLDL2, IDL, and LDL in the hypercholesterolemic group was increased input of VLDL2 (787 +/- 607 (SD) mg/day vs. 349 +/- 213 in normals, P < 0.01). VLDL1 apoB input was variably affected and not significantly different from normal. However, the plasma residence time of this subfraction was increased (0.15 +/- 0.07 days vs. 0.08 +/- 0.03 days in normals, (P < 0.001) due to a decreased fractional rate of direct catabolism. Fractional transfer rates (FTR) down the delipidation cascade and other fractional rates of direct catabolism were, overall, not significantly different from normal. The plasma residence time of VLDL2 apoB and LDL apoB was similar in hypercholesterolemic and normal subjects, while that of IDL apoB was slightly increased. Variation in LDL apoB mass within the hypercholesterolemic group correlated with VLDL1 apoB input (r = 0.58, P = 0.006), the fractional rate of transfer from IDL to LDL (r = 0.61, P = 0.003), and direct LDL input (r = 0.64, P = 0.002). The proportion of LDL apoB mass derived by direct, i.e., VLDL-independent input, varied from 5 to 50% and was inversely correlated with plasma triglyceride (r = -0.53, P = 0.014) and positively with HDL2 (r = 0.66, P = 0.002). In addition, the amount of direct LDL input was related to the amount of VLDL1 removed by direct catabolism (r = 0.53, P = 0.013). The analysis indicated that moderate hypercholesterolemia arose principally from overproduction of small VLDL, while variation in VLDL1 input and the IDL to LDL conversion rate (presumably hepatic lipase-mediated) modulated the extent of the elevation in LDL apoB.

Apolipoproteins B↗
PubMed1995

Development and application of a multicompartmental model to study very low density lipoprotein subfraction metabolism.

A multicompartmental model has been devised to explain apolipoprotein B (apoB) kinetics in very low density lipoprotein subfractions (VLDL1 Sf 60-400 and VLDL2 Sf 20-60), intermediate density (IDL Sf 12-20) and low density lipoproteins (LDL Sf 0-12). Normal and hyperlipemic subjects were given tracer doses of 131I-labeled VLDL1 and 125I-labeled VLDL2 and the metabolism of apoB in VLDL1, VLDL2, IDL, and LDL was followed over a period of 13 days. VLDL1 apoB and VLDL2 apoB clearance curves had an initial shoulder, a rapid decay, and a 'tail' of slowly metabolized lipoprotein. ApoB derived from VLDL1 appeared in IDL over 10-50 h and exhibited bi-exponential decay that was attributed to the presence of two metabolically distinct species. A further compartment was required to explain the observation that a substantial proportion of apoB from VLDL2 appeared and disappeared from the IDL density range faster than apoB derived from VLDL1 delipidation. Both of the more rapidly removed IDL species gave rise to LDL apoB that was also modeled as a heterogeneous entity with two plasma compartments. The final model, which has much in common with previous versions (M. Berman et al. 1978. J. Lipid Res. 19: 38-56), a multi-step delipidation pathway and slowly metabolized remnant compartments in VLDL, incorporates parallel delipidation routes in VLDL2, IDL, and LDL. These parallel pathways linked kinetic heterogeneity in VLDL with that in IDL and LDL.

Apolipoproteins B↗
PubMed1994

Diabetic dyslipidemia and atherosclerosis.

Non insulin-dependent diabetes mellitus is frequently accompanied by qualitative and quantitative abnormalities in plasma lipids and lipoproteins. Increased triglycerides and decreased HDL (high density lipoprotein)-cholesterol are commonly observed; these alterations are recognized risk factors for coronary heart disease. Moderately elevated plasma triglyceride-rich lipoproteins may contribute to the atherogenic process through remodelling of LDL (low density lipoprotein) and HDL particles. Good glycemic control, diet and, when necessary, treatment with fibrates will correct or partially reverse the abnormal lipoprotein profiles found in diabetic patients.

Coronary Disease↗
PubMed1994

Prevention of restenosis after coronary balloon angioplasty: rationale and design of the Fluvastatin Angioplasty Restenosis (FLARE) Trial. The FLARE Study Group.

Prevention of restenosis after successful percutaneous transluminal coronary balloon angioplasty (PTCA) continues to present the greatest therapeutic challenge in interventional cardiology. Experimental and pathological studies describe restenosis as no more than the biologic healing response to arterial injury. Studies of serial quantitative coronary angiography have demonstrated that this biologic process may be measured as the loss in minimal luminal diameter (MLD) from post-PTCA to follow-up angiography and that it is essentially ubiquitous and normally distributed. Thus, quantitative coronary angiography has become the gold standard for evaluation of the angiographic outcome of clinical trials of new agents and devices aimed at prevention of restenosis. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors inhibit biosynthesis of mevalonate, a precursor of non-sterol compounds involved in cell proliferation, and thus may control the neointimal response, which forms the kernel of restenosis. Experimental evidence suggests that fluvastatin may exert a greater direct inhibitory effect on proliferating vascular myocytes than other HMG-CoA reductase inhibitors, independent of any lipid-lowering action. The Fluvastatin Angioplasty Restenosis (FLARE) Trial was conceived, in collaboration between the Thoraxcenter, Erasmus University, Rotterdam, The Netherlands, and Sandoz Pharma, to evaluate the ability of fluvastatin 40 mg twice daily to reduce restenosis after successful single-lesion PTCA. Treatment of suitable patients begins 2 weeks before PTCA and continues after successful PTCA (residual diameter stenosis < 50%, without major cardiac complications) to follow-up angiography at 26 +/- 2 weeks. Restenosis is measured by quantitative coronary angiography at a core laboratory as the loss in MLD from post-PTCA to follow-up angiography. It is calculated (90% power, alpha = 0.05) that 730 evaluable patients will be needed to test the hypothesis that fluvastatin will reduce the expected post-PTCA loss in MLD by 40%. Serial lipid analysis will be carried out at a central laboratory. Trial evaluation is focused on the primary endpoint (change in MLD) but includes primary clinical endpoints (death, myocardial infarction, or the need for coronary artery bypass graft surgery or reintervention up to 40 weeks after PTCA) as well as secondary and tertiary clinical, angiographic, and laboratory endpoints. According to this methodologic approach, the effect of fluvastatin in luminal renarrowing and clinical events after successful PTCA as well as possible associations of lipid parameters with restenosis can be comprehensively investigated.

Angioplasty, Balloon, Coronary↗
PubMed1994

The provision of oral surgery services in England and Wales 1984-1991.

Data from the Department of Health and the Dental Practice Board demonstrate substantial increases in the volume of oral surgery performed in England and Wales both in the General Dental and Hospital Services during the period 1984-1991. In the General Dental Service, although the number of routine extractions decreased by 10%, the number of surgical procedures increased by 20%, with a substantial increase (33%) in the number of third molar extractions in the period 1988-1991. There have been no decreases in the annual rate of extractions of permanent and deciduous teeth in the GDS since 1987. In at least one Regional Health Authority, there was a five-fold increase in the number of oral surgery patients aged 0-9 years treated in the hospital service (1982-1991). Overall, although this study takes no account of extractions carried out in the Community Service, these findings suggest that numbers of deciduous extractions may have actually risen in some areas, particularly after 1987. In the Hospital Service there was a 55% increase in numbers of day-cases, from 30,090 (1984) to 46,499 (1990); a 10% increase in throughput of in-patients and a 13% decrease in numbers of people waiting for in-patient surgery. These changes were in the same direction as those in plastic and ENT surgery; though plastic surgery achieved a greater utilisation of day-care services. The implications of these changes and their possible effect on the future provision of oral and maxillofacial surgery services are discussed.

Apicoectomy↗
PubMed1994

The fibrates in clinical practice: focus on micronised fenofibrate.

Dietary measures, including calorie restriction and reduced fat intake, remain the mainstay of management in prevention of coronary heart disease (CHD). When this fails, drug therapy should be considered. Fibrates, a family of lipid lowering drugs, decrease plasma triglycerides and inhibit their synthesis. They are also reported to suppress cholesterol production in the liver. A disadvantage of fenofibrate is the poor solubility of the principal ingredient, with subsequent incomplete absorption after oral administration. Micronized fenofibrate, a new formulation chemically identical to the parent compound, has improved pharmacokinetic parameters which increase absorption, provide more stable plasma levels, and thus dosage can be decreased. The micronized formulation has been shown to be effective in reducing LDL cholesterol and triglycerides in patients with types IIa and IV hyperlipidemia, with increasing responsiveness to therapy in proportion to elevated baseline values of these parameters. This formulation has also been compared to simvastatin, an HMG-CoA reductase inhibitor. Results of a double-blind crossover study showed that both drugs reduced plasma cholesterol levels by similar amounts, and both produced similar increases in HDL cholesterol. The micronized formulation of fenofibrate thus provides improved efficacy in the prevention of CHD. In comparison to the standard formulation, micronised fenofibrate thus provides improved efficacy in the control of dyslipidemia and the prevention of CHD.

Adolescent↗
PubMed1994

Effects of ciprofibrate on LDL metabolism in man.

This study examined the effects of ciprofibrate therapy (100 mg/day) on plasma lipids, lipoproteins and low density lipoprotein (LDL) kinetic heterogeneity in moderately hypercholesterolaemic subjects. The drug lowered plasma triglyceride and cholesterol by 41% and 17%, respectively. Very low density lipoprotein (VLDL) cholesterol fell by 38%, LDL cholesterol fell by 22%, while the content of the lipid in high density lipoprotein (HDL) increased by 11%. LDL structural and metabolic heterogeneity were assessed before and during therapy in eight subjects. Density gradient centrifugation was used to fractionate LDL into three species. LDL-I, the least dense, was not affected by therapy whereas LDL-II and LDL-III were decreased by 28% (P < 0.01) and 31% (N.S.). Baseline turnover studies revealed that LDL catabolism was subnormal and this was the cause of the raised cholesterol in these subjects. Ciprofibrate therapy increased the apoLDL fractional catabolic rate (FCR) by 19%, principally by inducing a 38% enhancement (P < 0.03) in apoLDL removal by the receptor pathway. ApoLDL kinetics exhibited metabolic heterogeneity both before and during drug therapy. Analysis of plasma decay curves for the LDL tracer and urinary excretion data indicated that the lipoprotein comprised two metabolically distinct species, one with an FCR of about 0.50 pools/day (Pool A), the other with an FCR of about 0.18 pools/day (Pool B). Drug therapy decreased synthesis of and hence reduced the plasma mass of apoLDL in the slow metabolised pool B. This perturbation in synthesis was linked to the change in plasma triglyceride concentration. The resultant reduced proportion of pool B vs. pool A material accounted for the observed promotion of LDL receptor-mediated clearance. Ciprofibrate, therefore, produced beneficial changes in the plasma levels of VLDL, LDL and HDL and in the metabolism of LDL.

Adult↗
PubMed1994

Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk.

The concentration of plasma LDL subfractions is described in four groups of normocholesterolaemic (total plasma cholesterol < 6.5 mmol/l) male subjects consisting of men with and without coronary artery disease (CAD+/-), as determined by angiography, post-myocardial infarct survivors (PMI) and normal, healthy controls. The CAD(+) and PMI groups were distinguished from the CAD(-) and controls by raised concentrations of plasma triglyceride, very low density lipoprotein (VLDL) cholesterol, small, dense LDL (LDL-III density (d) 1.044-1.060 g/ml) and lower concentrations of high density lipoprotein (HDL) cholesterol and large, buoyant LDL (LDL-I d 1.025-1.034 g/ml). In all groups, a subfraction of intermediate density, LDL-II (d 1.034-1.044 g/ml), was the predominant LDL species but was not related to coronary heart disease risk. Plasma triglyceride showed a positive association with LDL-II (r = 0.51, P < 0.001) below a triglyceride level of 1.5 mmol/l. Above this threshold of 1.5 mmol/l, LDL-II and LDL-I showed significant negative associations with triglyceride (LDL-II r = -0.5, P < 0.001; LDL-I r = -0.45, P < 0.001). Small, dense LDL-III showed a weak positive association with triglyceride that became highly significant above the 1.5 mmol/l threshold (r = 0.54, P < 0.001). While age was positively related to LDL-II within the control subjects (r = 0.3, P < 0.05), there was no difference in the percentage abundance or concentration of LDL-III within control and CAD(-) subjects above and below the age of 40 years. Smoking was associated with a relative deficiency of the LDL-I subfraction (LDL-I to LDL-III ratio in smokers = 0.77, in ex-smokers = 0.95, in non-smokers = 1.89; P < 0.01), as was beta-blocker medication (% LDL-I, users vs. non-users, P < 0.05). Both of these effects could be explained by their primary influence on plasma triglyceride. Analysis of the frequency distributions for the three LDL subfractions revealed the concentration of small, dense LDL-III to be bimodal around a concentration of 100 mg (lipoprotein mass)/100 ml plasma. The calculation of odds ratios based on this figure indicated relative risk estimates of 4.5 (chi 2: P < 0.01) for the presence of coronary artery disease and 6.9 (chi 2: P < 0.001) for myocardial infarction.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Regional and supraregional biochemistry services in Scotland: a survey of hospital laboratory users.

AIM: To ascertain the views of Scottish hospital laboratory users on aspects of regional and supraregional biochemical services offered by the Institute of Biochemistry at Glasgow Royal Infirmary. METHODS: A questionnaire was circulated asking questions or inviting opinions under various headings, including current patterns of usage of the services provided, availability of information on specimen collection requirements and reference ranges, current arrangements for transport of specimens, turnaround times for delivery of reports, layout and content of request and report forms, quantity and quality of interpretive advice, potential changes in laboratory services, and overall impression of the services provided. Opportunities were provided for free text comment. The questionnaire was circulated in 1992 to heads of department in 23 Scottish hospital biochemistry laboratories. RESULTS: Twenty one replies were received. Services used widely included trace metals/vitamins (n = 20) and specialised endocrine tests (n = 19). Other services also used included specialised lipid tests (n = 13), toxicology (n = 12), thyroid function tests (n = nine), and tumour markers (n = eight). Fifteen laboratories used one or more of the services at least weekly. Most (n = 20) welcomed the idea of a handbook providing information on specimen collection and reference ranges. Nine identified loss of specimens as a problem. Other perceived problems included the absence of reference ranges from report forms, quantity and quality of interpretive advice, and turnaround times of some tests. Overall impressions of the service(s) offered were very good (n = 12); adequate (n = seven); poor (n = one). CONCLUSIONS: Useful information was obtained about patterns of use and transport arrangements. Areas identified as requiring follow up included provision of information, alternative ways of communicating reports, and improvement in quantity and quality of interpretive advice.

Attitude of Health Personnel↗
PubMed1994

Regulation of plasma HDL cholesterol and subfraction distribution by genetic and environmental factors. Associations between the TaqI B RFLP in the CETP gene and smoking and obesity.

This study investigated in a healthy population (n = 220) the association of the TaqI B restriction fragment length polymorphism (RFLP) in the cholesteryl ester transfer protein (CETP) gene with plasma high-density lipoprotein (HDL) cholesterol concentration and subfraction distribution. A raised HDL cholesterol level was found in B2B2 homozygotes (B2 cutting site absent) and was associated specifically with a 45% increase in HDL2 compared with B1B1 homozygotes (B1B1, 77 +/- 39 mg/100 mL, mean +/- SD; B2B2, 112 +/- 59 mg/100 mL; P < 0.01). Total plasma, very-low-density lipoprotein, and HDL triglyceride levels did not differ among the genotype groups, nor did plasma apolipoprotein AI levels (B1B1, 1.45 +/- 0.35 mg/mL, mean +/- SD; B2B2, 1.56 +/- 0.33 mg/mL). Thus, the genetic variation appeared to be independent of metabolic factors that are known to regulate HDL levels. Plasma CETP exchange activity was unlikely to be the cause of the association, since it did not differ between genotype groups and was not correlated with HDL2 concentration. Multivariate analysis demonstrated that the TaqI B polymorphism had an effect on HDL cholesterol and HDL2 that was independent of age, sex, body mass index, oral contraceptive use, exercise, alcohol consumption, and plasma triglycerides. In smokers, the presence of the B2B2 genotype did not result in increased HDL cholesterol or HDL2, whereas in obese subjects, the difference between B1B1 and B2B2 individuals was diminished. We conclude that the TaqI B RFLP is associated with a quantitatively significant effect on plasma HDL2 levels that is independent of plasma triglycerides and interacts with lifestyle factors.

Adult↗
PubMed1994

Determinants of LDL subfraction distribution and concentrations in young normolipidemic subjects.

Human low-density lipoproteins (LDLs) comprise a spectrum of particles that vary in size, density, chemical composition, metabolic behavior, and atherogenicity. To identify determinants of this heterogeneity, we measured the percent distribution and plasma concentration of the three major LDL subfractions in 34 young healthy subjects. These parameters were correlated in univariate and multivariate analyses with various body and lifestyle factors; plasma lipids and lipoprotein; and the activities of cholesteryl ester transfer protein, lipoprotein lipase, and hepatic lipase (HL). Women (n = 15) had significantly more large, buoyant LDL (LDL-I; density, 1.025 to 1.034 g/mL) and high-density lipoprotein2 (HDL2) than men (n = 19). Both the percentage and concentration of LDL-I were correlated negatively with very-low-density lipoprotein triglycerides (VLDL-TG) and HL; they were correlated positively with HDL-cholesterol (HDL-C) and HDL2. In addition, percent LDL-I was negatively correlated with plasma triglycerides, VLDL-C, LDL-C, and apo-lipoprotein (apo) B concentrations. The concentrations of intermediate and small, dense LDL (LDL-II and LDL-III; density, 1.034 to 1.044 and 1.044 to 1.060 g/L, respectively) were positively correlated with LDL-C. LDL-III concentrations were also related to plasma cholesterol and apoB concentrations and HL activity. On multivariate analyses, approximately one third of the variability in LDL-I was explained by HL and plasma triglycerides. More than 80% of the variation in LDL-II was accounted for by a model that combined LDL-C and plasma apoB with body mass index and VLDL-TG.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Lipoprotein metabolism. An overview.

The biological benefits of lipids as sources of energy and precursors of cell components have led to the evolution of a complex plasma lipoprotein transport system, through which gram quantities of cholesterol, triglyceride, and phospholipid pass each day. A wide variety of tissues make demands on this pool. The adrenal glands and gonads avidly assimilate lipoprotein cholesterol for the production of steroid hormones, and rapidly dividing intestinal villus cells take up the sterol for membrane synthesis. Metabolically active tissues such as skeletal muscle use plasma triglyceride for energy production, while in times of surfeit this lipid is directed into adipocytes for storage. Two organs, the liver and intestine, play a particularly important role in corporeal lipid metabolism, and together are responsible for the majority of lipoprotein synthesis and catabolism. In the plasma, lipid transport is regulated by specific apolipoproteins (apo), lipoprotein receptors, lipolytic enzymes and transfer proteins, which act in concert to maintain the balance of cholesterol and triglyceride homeostasis in tissues and plasma; their malfunction may cause or contribute to the development of dyslipidaemia.

Apolipoproteins B↗
PubMed1994

Transition from school to community living.

The transition process by which a student with moderate to severe disabilities is prepared to leave the school setting and enter into employment and community living is legally mandated and includes provisions for occupational therapy and other related services. This transition requires a team approach in which members collaborate to determine objectives with the student and his or her family in the domains of domestic, community, recreational, and vocational living. Assessment and intervention focus on functional activities that are chronologically age-appropriate and environmentally based. This focus on real life activities is a departure from the prereadiness skills and simulations used by some occupational therapists in school systems. This literature review describes the transition from school to community living, discusses methods to increase parental participation, and provides examples of functional assessments and intervention strategies pertinent to occupational therapy practice for persons with moderate to severe disabilities.

Adolescent↗