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Biomedical subjects

J Shepherd

Publications and source records attributed to J Shepherd.

At least 181 records · Page 10Linked to original sources
PubMed1994

Violent crime: the role of alcohol and new approaches to the prevention of injury.

Almost all evidence of a link between alcohol consumption and violence is available only in the form of aggregate data. This is unsatisfactory and case-control investigations and studies which relate injury severity to blood alcohol levels are needed. In the few closely controlled studies which have been performed, increased risk of injury in assault has been linked with binge consumption of more than about 8 units, and above average weekly consumption only in those over 25 years. Raising the minimum purchasing age for alcohol to 21 years, learning to drink responsibly with parents, especially fathers, and the adoption of tempered glassware are all achievable objectives which would reduce alcohol-related injury. The use of sobriety-checkpoints (breath testing though not by the police) and other situational prevention programmes need to be evaluated in relation to reducing injury sustained in violent crime. Proactive, community policing has been shown to reduce levels of alcohol-related violent crime, in contrast to more reactive, defensive and confrontational policing. The concept of 'capable guardianship' to establish and maintain social control of young delinquents needs to be extended, particularly near known foci of violence such as bars and adjacent fast-food outlets and taxi-ranks.

Alcohol Drinking↗
PubMed1994

Gynaecological cytology and pelvic ultrasonography in patients with breast cancer taking tamoxifen compared with controls.

The objective of this study was to look at the effect of tamoxifen on the endometrium by comparing gynaecological cervical and endometrial cytology in breast cancer patients on tamoxifen for 3 years compared with controls. In addition, pelvic ultrasonography was employed to detect ovarian abnormalities and to measure endometrial thickness. Patients followed-up after primary surgical therapy for breast cancer were invited for gynaecological assessment consisting of clinical examination pelvic ultrasonography and a cervical smear and endometrial sampling. The patients taking tamoxifen (n = 49) has been on adjuvant hormone therapy for a minimum of 3 years. Control patients (n = 45) were also being followed-up for breast cancer. On examination the tamoxifen patients had very similar clinical findings to the control patients with regard to the cervix (normal in 84% of tamoxifen takers compared to 87% of controls). The uterus was clinically enlarged in eight patients on tamoxifen and in none of the control patients (P = 0.006) and only one ovarian cyst was clinically detectable in a patient taking tamoxifen. Pelvic ultrasonography between the two groups of patients was not statistically different (chi 2 test) and ovarian cysts were noted in nine patients from each group (tamoxifen patients 18% vs control patients 20%, n.s.). There was a highly significant difference in endometrial thickness in premenopausal patients (9.2 mm) compared with postmenopausal patients (6.4 mm, P = 0.001). There was also a suggestion that endometrial thickness was greater in tamoxifen treated patients (P = 0.08). In general, a greater proportion of patients taking tamoxifen had cervical and endometrial cells exhibiting hyperplastic nuclei, and in endocervical smears, this difference achieved statistical significance (Mann-Whitney test, P = 0.046). These findings show that a significantly increased proportion of patients taking tamoxifen had endocervical nuclear hyperplasia, and a trend towards increased endometrial thickness. These findings confirm that tamoxifen has mild oestrogenic activity. However, the lack of any difference in the incidence of dysplasia suggests that the carcinogenic potential of tamoxifen on the uterus is very low and the beneficial effects of tamoxifen as an adjuvant therapy for breast cancer outweighs its theoretical risks.

Adolescent↗
PubMed1994

Action of danazol on plasma lipids and lipoprotein metabolism.

Danazol, a weakly androgenic, heterocyclic compound with anabolic properties, is used primarily in the treatment of endometriosis and other gynecological complaints. Early reports indicated that the drug had little effect on plasma lipid (cholesterol and triglyceride) levels but recently concern has been expressed over more subtle changes reported in plasma lipid and lipoprotein metabolism after danazol treatment. Therapy produces a rapid reduction in high density lipoprotein (HDL) cholesterol (particularly in the putatively cardioprotective HDL2 subfraction) coupled with a rise in the pro-atherogenic low density lipoprotein (LDL). These apparently unwanted actions are balanced against a possibly beneficial reduction in the atherogenic lipoprotein(a) fraction. The mechanism of these changes induced by danazol is unknown but probably relates to effects on hepatic lipase, LDL receptor and lecithin cholesterol acyl transferase activity. While it is prudent to recognize the potential detriment that may follow these perturbations, concern is only warranted where therapy is prolonged (> 12 months) or given to subjects with a high background risk of ischemic heart disease.

Cholesterol↗
PubMed1993

The ins/del polymorphism in the signal sequence of apolipoprotein B has no effect on lipid parameters.

The 'ins/del' polymorphism in the signal sequence of apolipoprotein B alters the hydrophobicity of the signal sequence and therefore would be expected to affect the rate of production of apolipoprotein B (apo B) and the plasma concentrations of lipoproteins containing this apolipoprotein. We sought evidence for an association with plasma lipid levels and this polymorphism in two studies, one using a normal randomly selected population (N = 188) and another using a mildly hypercholesterolaemic group of men aged 45-64 (N = 360). The frequency of the rarer, 'del' allele, was the same in both groups. Likewise no differences in serum cholesterol, serum triglycerides, very low density lipoprotein, low density lipoprotein or high density lipoprotein were seen comparing homozygotes for the signal sequence allele within either group.

Apolipoproteins B↗
PubMed1993

Comparison of clinical treatment decisions with US National Institutes of Health consensus indications for lower third molar removal.

Treatment decisions about lower third molar surgery have important clinical and cost implications. Although indications for surgery have been the subject of a National Institutes of Health (NIH) consensus conference at which several unambiguous criteria were agreed, no prospective investigations have been carried out to compare clinic treatment decisions with these consensus criteria. Treatment decisions made by six Hospital Service oral surgeons were therefore evaluated for 72 consecutive patients (28 men, 44 women) aged 15-44 years (mean age 25 years), referred for lower third molar assessment. The presence of local disease; recurrent pericoronitis; caries not amenable to restorative measures; follicular cyst formation; internal/external resorption and periodontal disease was recorded by an independent observer immediately after treatment planning had been completed. Of the 139 third molars present, 55 were unerupted, 79 partially erupted and 5 fully erupted. Thirty patients had been scheduled for surgery under general anaesthesia (GA), 36 under local anaesthesia and six patients had not been scheduled for surgery. A total of 42 teeth, according to NIH consensus criteria, had no indications for removal, of which 27 had been scheduled for surgery. These excluded disease-free contralateral teeth that had been scheduled for removal under GA. When a single episode of pericoronitis was excluded as a valid indication, 39 teeth did not meet criteria for removal but had been scheduled for surgery. It was concluded that two-thirds of lower third molars not meeting NIH consensus criteria for surgery had been scheduled for removal. The reasons for this, which may include inappropriate criteria, require further research.

Adolescent↗
PubMed1993

Frequency of the XbaI, EcoRI, PvuII and MspI polymorphisms of the apolipoprotein B gene in relation to hypercholesterolaemia in the general population.

In this study the frequencies of the genotypes of four restriction fragment length polymorphisms in the apolipoprotein B gene (XbaI, EcoRI, PvuII and MspI) are compared between groups of normolipidaemic and diet resistant hypercholesterolaemic individuals as possible markers for the influence of this gene on plasma cholesterol levels. In the first part of the study genotypes of all four markers were determined in 92 normolipidaemic (mean cholesterol 5.6 + 0.8 mmol/l) and 79 diet resistant hypercholesterolaemic (mean cholesterol 7.8 + 0.7 mmol/l) individuals seen in a local health centre screening programme for coronary heart disease risk factors. No significant difference was seen in the frequencies of the EcoRI and PvuII genotypes between the two groups. There was significant enrichment of both the XbaI X2 (presence of cutting site) allelic frequency and of the MspI M1M2 (M2 absence of cutting site, rarer allele) genotype frequency in the hypercholesterolaemic group. In the second part of the study an independent larger group of individuals, seen in a multicentre screening programme across the city of Glasgow, were genotyped for the two potentially significant polymorphic sites (XbaI and MspI). From this second screening programme 188 age matched normolipidaemic males (mean cholesterol 5.0 +/- 0.8 mmol/l) were compared with 186 males who were still hypercholesterolaemic (mean 8.2 +/- 0.6 mmol/l) after three months dietary intervention. The hypercholesterolaemic individuals in this second study did not show a significant enrichment of the XbaI X2 allele but again showed a highly significant enrichment of the MspI M1M2 genotype. This genetic effect may relate directly to the charge change from arginine to glutamine at amino acid 3611 caused by the MspI mutation or to an as yet unknown functionally significant mutation in linkage disequilibrium with this site.

Adult↗
PubMed1993

An increased incidence of apolipoprotein E2/E2 and E4/E4 in retinitis pigmentosa.

Previous studies from our laboratory have shown that retinitis pigmentosa (RP), a family of hereditary retinal degenerations, is often accompanied by abnormal levels of cholesterol or polyunsaturated fatty acids. The requirement of the retina for n-3 fatty acids is well known, and a defect in the supply of these lipids (e.g., by apolipoproteins) could affect the course of the disease. The present study confirms and extends a report on apolipoprotein E (apo E) isoforms in German RP patients [Jahn, Oette, Esser, Bergmann, and Leiss, (1987) Ophthalmic Res. 19, 285-288] which showed a tenfold increased frequency of the E2/E2 phenotype compared to the average German population. In our study, apo E phenotypes were determined in the probands of 100 Scottish RP families. The findings revealed a 4-fold increase in the incidence of E2/E2 and an 8-fold increase in E4/E4 compared to a Scottish control population. These increases were statistically significant at the P < 0.05 and P < 0.01 levels, respectively. To investigate the possibility that some of these apparent E2/E2 or E4/E4 phenotypes might actually be new apo E mutations, we examined the behavior of the apo E on sodium dodecyl sulfate-polyacrylamide gels (E2 migrates anomalously) and on isoelectric focusing gels following cysteamine modification of cysteines. These studies showed that two RP patients possibly had new apo E mutations, though amino-terminal sequence analysis revealed no changes in the sequence of the first 19 residues; further sequence analysis is obviously warranted.

Apolipoproteins E↗
PubMed1993

Plasma lipid transport in the horse (Equus caballus).

1. Equine plasma contains lipoproteins corresponding to very low density (VLDL), low density (LDL) and high density lipoproteins (HDL). 2. HDL accounts for approximately 60% of plasma lipoprotein mass and consists of a single population of particles. 3. LDL is heterogeneous comprising three discrete subfractions. 4. Two proteins are found in the region of apolipoprotein (apo) B-100 in VLDL and LDL and a third similar to apoB-48 is in VLDL. 5. Lecithin:cholesterol acyl transferase is active in plasma and hepatic lipase and lipoprotein lipase are evident in post-heparin plasma. 6. There is no significant cholesteryl ester transfer protein activity.

Animals↗
PubMed1993

High density lipoprotein metabolism in the horse (Equus caballus).

1. Apolipoprotein A-I dependent lecithin:cholesterol acyl transferase (LCAT) activity was identified in equine lipoprotein deficient plasma (LPDP). 2. LCAT activity showed no breed or sex variation, and was unaltered postprandially. 3. There was no significant cholesteryl ester transfer activity in equine LPDP. 4. Hydrophobic interaction chromatography on phenyl sepharose failed to unmask transfer activity or identify an inhibitor of cholesteryl ester transfer. 5. In 12 Shetland ponies, plasma high density lipoprotein (HDL) concentrations were positively correlated with those of triglyceride, but not with the activities of LCAT, lipoprotein lipase or hepatic lipase.

Animals↗
PubMed1993

Response of plasma low density lipoprotein subfractions to oestrogen replacement therapy following surgical menopause.

OBJECTIVE: Epidemiological studies suggest that postmenopausal oestrogen replacement reduces the incidence of cardiovascular disease. The purpose of this study was to establish the effects of oestrogen replacement therapy on subfractions of plasma low density lipoprotein in bilaterally oophorectomized women. DESIGN: In a placebo controlled, double-blind study, patients were randomized on a two to one basis to receive either oestradiol valerate (2 mg/day) or placebo respectively for a period of 16 weeks. PATIENTS: Seventeen women aged 28-51 years who had all had hysterectomy and bilateral oophorectomy at least 2 months before recruitment were assigned to either the active (n = 12) or placebo (n = 5) group. MEASUREMENTS: Plasma lipids, lipoproteins, apolipoproteins and LDL subfractions were determined immediately before and after the treatment period. LDL subfractions were isolated directly from plasma by density gradient ultracentrifugation within 24 hours. Non-parametric statistical analysis was carried out within each group using Wilcoxon's signed rank test for matched pairs. RESULTS: After 16 weeks of treatment, HDL cholesterol, apo A-I and HDL-2 were increased in the group receiving oestrogen (HDL cholesterol +12%, P < 0.01; apo A-I +14%, P < 0.01; HDL-2 +24% P < 0.01). While there were no significant changes in serum cholesterol, LDL cholesterol or triglycerides, the proportion and concentration of the least dense LDL-I subfraction was decreased significantly (-27%, P < 0.05). The LDL subfraction of intermediate density (LDL-II) was decreased in eight subjects, while small, dense LDL-III was unaffected. Overall, these changes resulted in an apparent shift in the distribution of LDL subfractions towards small, dense LDL-III, although there was no net increase in the latter. CONCLUSION: In view of a similar and characteristic response of LDL subfractions to hypolipidaemic drugs that enhance the clearance of LDL via the LDL receptor, the present findings suggest that oestrogen promotes the preferential removal of LDL-I and II by activating LDL receptors. As this effect is normally associated with a reduction in the circulating level of LDL, it should not be regarded as an unfavourable response to oestrogen replacement therapy.

Adult↗
PubMed1993

Smoking and plasma lipoproteins in man: effects on low density lipoprotein cholesterol levels and high density lipoprotein subfraction distribution.

In a survey of a healthy population (n = 197), LDL cholesterol, plasma triglycerides and VLDL triglycerides were found to be substantially increased and plasma HDL cholesterol decreased in smokers. The lipid-associated atherogenic risk in smokers as assessed by the LDL/HDL ratio was significantly higher [2.89 (SD 1.18, n = 63)] than in non-smokers [2.38 (SD 0.98, n = 86) P < 0.01]. The lower HDL level found in smokers was explained by a lower HDL-2 subfraction as determined by analytical ultracentrifugation. HDL 2b, 2a and 3a, measured by gradient gel electrophoresis, were all lower in the smokers but this was only significant for HDL 2a. Smoking had no effect on Lp(a) levels. HDL cholesterol and HDL-2 were strongly negatively correlated whereas LDL cholesterol and LDL/HDL ratio were strongly positively correlated with the plasma triglyceride concentration. There was a small but significant reduction in plasma CETP activity [non-smokers 49% t/microliter (SD 17, n = 90), smokers 43% t/microliter (SD 17, n = 66) P < 0.05] but CETP activity was not correlated with any measure of HDL in this population. Smoking was found to be an important independent contributor to the variation in plasma triglyceride, HDL, HDL-2 and LDL/HDL ratio. After correcting for sex, age, BMI, alcohol consumption, oral contraceptive use and plasma triglycerides smoking was still found to be significantly associated with HDL and the LDL/HDL ratio. Upon adjustment for covariant factors the mean differences between smokers and non-smokers for HDL cholesterol, HDL-2 and LDL/HDL were 0.15 mM, 16 mg dl-1 and 0.39 respectively. There appeared to be important sex differences in the influence of smoking on plasma lipoproteins. In women the main impact of smoking was on triglyceride levels and they in turn affected LDL and HDL. In contrast, in men, smoking had little impact on triglycerides and affected HDL more directly. We conclude that smoking cigarettes has an important effect on plasma lipoprotein metabolism through multiple mechanisms.

Adult↗
PubMed1993

Effects of simvastatin on apoB metabolism and LDL subfraction distribution.

Seven moderately hypercholesterolemic subjects were studied before and after 10 weeks of simvastatin therapy (20 mg/day). Therapy reduced low density lipoprotein (LDL) cholesterol by 39% (p < 0.001), whereas high density lipoprotein and very low density lipoprotein (VLDL) cholesterol were unchanged. Apolipoprotein (apo) B-containing lipoproteins were divided into VLDL1 (Sf 60-400), VLDL2 (Sf 20-60), intermediate density lipoprotein (IDL) (Sf 12-20), and LDL (Sf 0-12), and metabolic changes were sought in dual-tracer VLDL1 and VLDL2 turnover studies. VLDL1 apoB pool size was unaltered by therapy, as were its rates of synthesis, catabolism, and delipidation to VLDL2. Similarly, the VLDL2 apoB pool size was unchanged, but its metabolic fate was altered. The IDL pool size fell significantly (27%, p < 0.01) due entirely to an increased fractional catabolism of the lipoprotein. In our subjects, the circulating mass of LDL apoB decreased (49%, p < 0.01) primarily due to a reduction in its synthesis. Before therapy, 30% of the apoB entering the delipidation cascade in these hyperlipidemic subjects was converted to LDL. On therapy the input remained the same, but direct catabolism from VLDL2 and IDL was increased (p < 0.05), and as a result only 16% eventually appeared in LDL. These kinetic changes were associated with a fall in particle cholesteryl ester content throughout the delipidation cascade. We also observed a link between LDL kinetics and its subfraction distribution. Simvastatin influences the metabolism of LDL, IDL, and VLDL2 but not VLDL1.

Adult↗
PubMed1993

Fenofibrate and LDL metabolic heterogeneity in hypercholesterolemia.

Metabolic heterogeneity in low density lipoprotein (LDL) may be detected by examination of the daily urinary excretion rate of radioactivity after injection of trace-labeled lipoprotein. Two distinct pools are observed within LDL. The first (pool A) is cleared rapidly from the plasma, whereas the second (pool B) is catabolized more slowly. In the present study we examined LDL metabolism in seven hypercholesterolemic subjects (six women and one man) before and during fenofibrate therapy. Comparison with normocholesterolemic individuals showed that the pretreatment high LDL levels in the hypercholesterolemic subjects resulted from an accumulation of apoprotein-LDL (apo-LDL) mass in pool B (2,077 +/- 174 mg versus 787 +/- 70 mg in normal subjects, p < 0.002). Pool A apo-LDL was present at normal levels (approximately 1,000 mg), although its fractional catabolic rate was reduced (0.39 +/- 0.06 versus 0.61 +/- 0.03 pool/day in normal subjects, p < 0.01). Fenofibrate therapy (100 mg t.i.d. for 8 weeks) produced substantial reductions in plasma cholesterol (29%; p < 0.001), triglycerides (36%; p < 0.001), and LDL cholesterol (30%; p < 0.001). The latter was associated with a 30% decrease in circulating apo-LDL mass (2,312 +/- 200 mg versus 3,279 +/- 264 mg before treatment, p < 0.005). This resulted from a combination of two effects. First, although overall LDL apoprotein B production did not change, there was a shift from pool B to pool A. Pool A input was 400 +/- 74 mg/day pretreatment versus 706 +/- 62 mg/day on fenofibrate; pool B input was 422 +/- 35 mg/day pretreatment versus 258 +/- 41 mg/day on the drug. At the same time, catabolism of pool A rose from 0.39 +/- 0.06 to 0.66 +/- 0.08 pool/day (p < 0.05). We hypothesize that the shift from pool B to pool A resulted from a drug-induced decrease in the particle size of very low density lipoprotein made by the liver, which in turn favored the formation of more rapidly catabolized LDL. Overall, the rate of apo-LDL degradation by the receptor route (as detected using a combination of native and 1,2-cyclohexanedione-modified LDL tracers) rose 43% on the drug, whereas the amount cleared by the receptor-independent pathway did not change. Fenofibrate, therefore, appears not only to promote LDL catabolism via the receptor-mediated pathway but also, by lowering plasma triglyceride levels, inhibits the formation of slowly metabolized, potentially atherogenic LDL particles.

Aged↗