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Biomedical subjects

J Shepherd

Publications and source records attributed to J Shepherd.

At least 235 records · Page 13Linked to original sources

Progression and regression of atheroma.

Normal human arteries accumulate lipid in the intima with increasing age. These lipids are laid down in proportion to their distribution in low-density lipoprotein, suggesting that they are derived from this source. With their accretion, the amount of cholesterol and its esters in the subintimal space increases significantly, leading to the development of insoluble crystals which are difficult to remove by any therapeutic intervention. It has been shown that treatment with a low-cholesterol diet combined with lipid-lowering drug treatment can halt progression of atherosclerotic lesions, but as yet ther is no conclusive evidence that consistent lesion regression is possible.

Adult↗

Koilocytotic atypia and underlying dysplasia.

BACKGROUND: Several studies have examined the agreement between Papanicolaou smear cytology and subsequent biopsy results in the diagnosis of cervical dysplasia. However, few studies have focused specifically on koilocytotic (KC) atypia. Given the increasing frequency of reporting KC atypia on Papanicolaou smears, we sought to obtain more information on the relationship between Papanicolaou smears and subsequent colposcopically directed cervical biopsies. METHODS: Retrospectively, we compared the Papanicolaou smears and colposcopically guided biopsy results for 132 college women who had abnormal Papanicolaou smears (KC, cervical intraepithelial neoplasia [CIN], or reactive atypia [RA]). Data were compiled through systematic review of the charts of these women. The cervical biopsies were taken 6 months or less after the Papanicolaou smears. RESULTS: Of 99 women having only KC atypia on cytology, histology revealed concordance in 51 cases and underlying dysplasia in 16 cases. Only one biopsy revealed CIN III, and no biopsies showed invasive carcinoma. We also noted variation in the histologic results between the laboratories that analyzed the biopsy specimens. In comparing the biopsy results after one or two KC atypic Papanicolaou smears 6 months or less apart, we found no statistically significant difference. CONCLUSIONS: These findings suggest that physicians who obtain an initial Papanicolaou smear read as KC atypia could obtain a second smear 3 months later to determine if there is persistent KC atypia before advising a patient to have cervical biopsy. In addition, physicians also should know the limitations of the laboratories providing them with information.

Adolescent↗

An investigation of the relationships between body condition and plasma lipid and lipoprotein concentrations in 24 donkeys.

Obese donkeys are susceptible to a hyperlipaemic crisis characterised by high plasma triglyceride concentrations. In this study, the relationships between the body condition of 24 donkeys and their basal lipid metabolism were investigated. Plasma cholesterol, triglyceride and lipoprotein cholesterol concentrations were measured in healthy donkeys classified according to their body condition as thin, ideal or obese. There were significant differences between the groups in the concentrations of triglyceride and very low density lipoprotein (VLDL), which increased in concentration with body condition (P less than 0.05). Cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) concentrations were similar in all the groups. Triglyceride and VLDL concentrations were positively correlated with body weight (r = 0.82) and plasma free fatty acid concentration (r = 0.48). There were no significant differences in basal plasma concentrations of insulin or cortisol. These results suggest that obesity in donkeys is associated with changes in lipid and lipoprotein metabolism that might predispose the animals to hyperlipaemia.

Animals↗

Fear of crime.

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Adolescent↗

Phenotypic expression in spontaneously transformed cultured rat liver epithelial cells.

Five clonal cell strains of an early-passage normal rat liver epithelial cell line were transformed spontaneously using the protocol of "selective culture" condition. Twelve cell lines were established from the tumors produced after injecting these transformed cells into 1-day-old syngeneic rats. The phenotypic expressions of these spontaneously transformed tumor cell lines were studied and compared to those of cell lines obtained from tumors produced by rat liver epithelial cells transformed by N-methyl-N'-nitro-N-nitrosoguanidine. Like the chemically induced tumor cells, spontaneously transformed tumor cells exhibited phenotypic heterogeneity in the expression of isoenzymes, proto-oncogenes, growth factors and their receptors, and cellular responses to the effect of growth factors. However, unlike the chemically induced tumor cells, these spontaneously induced tumor cells did not express the "resistant phenotypes" characteristic of chemically induced or promoted tumors. Although all the spontaneously induced tumor cell lines expressed variable amounts of transforming growth factor-alpha mRNA, it was not functionally coordinated with the expression of its receptor, the epidermal growth factor receptor. Thus, spontaneously transformed rat liver epithelial cells demonstrate both similarity and diversity in their phenotypic expression when compared to their chemically induced counterpart. This model of spontaneous transformation of cultured rat liver epithelial cells may be useful for the mechanistic study of non-chemically induced carcinogenesis.

Animals↗

Genotoxicity of pancreatic chemical carcinogens to propagable cultured normal pancreatic epithelial cells.

The cytotoxic and DNA-damaging effects of the pancreatic carcinogens azaserine, streptozotocin, and N-nitrosobis(2-oxyopropyl)amine (BOP) on propagable cultured normal rat pancreatic epithelial cells have been studied. All three chemicals in micromolar concentrations produced cytotoxicity to these cells. The concentrations that caused 50% reduction in colony formation (LD50) were approximately 0.3 mM for azaserine, 0.4 mM for BOP, and 2 mM for streptozotocin. Comparatively, the LD50 for N-methyl-N'-nitro-N-nitrosoguanidine was 3 microM. The toxicity of both azaserine and BOP did not require exogenously added S9 microsomal enzymes, indicating that the cells were capable of metabolic activation of these carcinogens. All three compounds induced unscheduled DNA synthesis, thus suggesting their mutagenic and carcinogenic potential in these cultured cells.

Animals↗

Postprandial lipemia, fenofibrate and coronary artery disease.

This report describes the response of patients with severe coronary artery disease to a dynamic fat load test and monitors the change induced by fenofibrate therapy. The presence of disease was associated with prolonged and exaggerated hypertriglyceridemia following the meal and with lower basal HDL cholesterol and HDL subfraction masses. A further indicator of risk was the persistence of increased amounts of retinyl palmitate in the plasma of severely affected individuals 24 h after its ingestion with the meal. These observations are consistent with the proposal that the clearance of chylomicrons and their remnants is impaired in coronary atherosclerosis. Fenofibrate reduced alimentary lipemia following the fat load in both normo- and hypercholesterolemic subjects. This was associated with a 10% rise in plasma HDL cholesterol levels. The improvement in chylomicron catabolism probably derived from a 37% increase (P less than 0.001) in lipoprotein lipase activity induced by fenofibrate. Hepatic lipase on the other had was only slightly affected by treatment.

Adult↗

Genetic variation in the cholesteryl ester transfer protein and apolipoprotein A-I genes and its relation to coronary heart disease in a Sri Lankan population.

The influence of variation in the genes for cholesteryl ester transfer protein and apolipoprotein A-I was investigated in 95 patients with coronary heart disease and 95 matched control subjects of South East Asian extraction. Restriction fragment length polymorphisms (RFLPs) linked to the cholesteryl ester transfer protein gene TaqIA and TaqIB, and to the apolipoprotein A-I gene SstI, were examined to investigate the extent of genetic variation at these loci. None of the alleles defined by these RFLPs were associated with increased coronary risk. Analysis of the data by division of high density lipoprotein-cholesterol levels into tertiles showed a trend of a higher frequency of B1 allele (presence of the TaqIB site) with reduced high density lipoprotein levels. The B1 allele was more frequent in control subjects, with low high density lipoprotein levels (P less than 0.02), but not in coronary heart disease patients. The differences became significant for both groups (P less than 0.05) when the data of non-smokers were analysed separately.

Apolipoprotein A-I↗

Rapid isolation of low density lipoprotein (LDL) subfractions from plasma by density gradient ultracentrifugation.

High resolution density gradient ultracentrifugation (DGUC) and non-denaturing gradient gel electrophoresis (GGE) indicate that low density lipoprotein (LDL) in both normal and hyperlipidaemic subjects is composed of overlapping particle populations. A new centrifugation procedure has been developed which permits the separation of LDL subspecies directly from plasma within 24 h. The profiles obtained were analogous to those seen on gradient gel electrophoresis. LDL was divided into 3 fractions. The plasma concentration of LDL-I seen in young females was twice that in men (85.6 +/- 28.8 vs. 42.3 +/- 25.7 mg/dl, P less than 0.005). LDL-II was not significantly different in any group while LDL-III was specifically elevated in coronary artery disease (CAD) patients (207.1 +/- 92.6 mg/dl in CAD vs. 87.4 +/- 79.6 mg/dl in normal men, P less than 0.05). The presence of small, dense LDL detected either by density gradient centrifugation or gel electrophoresis was associated with raised triglyceride (TG) and low high density lipoprotein (HDL) cholesterol and may be a risk marker for coronary artery disease.

Adolescent↗

Low-density lipoprotein metabolism in the nephrotic syndrome.

Hyperlipidemia is a consistent feature of the nephrotic syndrome. In this study, low-density lipoprotein (LDL) metabolism has been investigated in nine patients with nephrotic syndrome and varying degrees of proteinuria. In subjects with moderate proteinuria (less than 10 g/d), total plasma cholesterol values were elevated to approximately 160% of normal due mainly to an increase in circulating LDL cholesterol. Metabolic studies showed that a defect in LDL clearance via the receptor pathway was responsible for its accumulation. The total amount of LDL apolipoprotein catabolized by this mechanism was only 55% of the value seen in controls; 60% more LDL was channelled into alternative, receptor-independent, catabolic pathways. Heavier proteinuria was associated with substantial increases in plasma triglyceride and very-low-density lipoprotein (VLDL) levels. The defect in LDL catabolism was aggravated by oversynthesis of the lipoprotein, which expanded the plasma LDL pool to 250% of normal. These observations indicate that the hyperlipidemia of the nephrotic syndrome is multifactorial in origin. The altered catabolism of LDL may be important in predisposing these subjects to premature atherosclerosis.

Adult↗

A comparative study of maxillo-facial trauma in Bristol and Bordeaux.

Consecutive patients with maxillofacial fractures who attended departments of maxillofacial surgery in Bristol and Bordeaux during 1985-1986 were surveyed prospectively to determine differences in demography and aetiology and patterns of injury. 1,652 patients were included: 1,146 in Bordeaux and 506 in Bristol. Significantly more patients with nasal complex fractures were treated in Bordeaux reflecting management of these injuries by oto-rhino-laryngologists in Bristol. Maxillary fractures were comparatively more frequent in Bordeaux, reflecting a higher incidence of road accidents. Significantly more assault victims were treated by maxillofacial surgeons in Bristol, though per capita alcohol consumption by age and sex matched individuals was greater in France than in the U.K. Incidence of fracture was 18/100,000 hospital catchment population/year in Bordeaux, compared to 32/100,000 population/year in Bristol; reflecting that in contrast to Bristol, specialists in private practice outside the regional centre treated patients with fractures in S. W. France. Differences in aetiology of injury could be explained by cultural factors. Formal twinning arrangements and EEC membership provide excellent opportunities for postgraduate education, training and collaborative clinical research.

Accidents, Traffic↗

Polymorphisms in the gene coding for cholesteryl ester transfer protein are related to plasma high-density lipoprotein cholesterol and transfer protein activity.

1. Cholesteryl ester transfer protein activity may have a physiological effect on high-density lipoprotein levels. 2. We examined restriction fragment length polymorphisms associated with the cholesteryl ester transfer protein gene and the apolipoprotein AI gene in a group of 60 unrelated subjects selected from an initial survey of 5000 subjects on the basis of their high-density lipoprotein levels being high or low at the extremes of the distribution. The activities of cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase (phosphatidylcholine-sterol acyltransferase, EC 2.3.1.43) were also determined. Analysis by selection of those with a low high-density lipoprotein cholesterol level (less than or equal to 1.1 for males, less than or equal to 1.2 for females) gave 32 individuals with 24% B2 alleles. Selection of subjects with a high-density lipoprotein cholesterol level (less than or equal to 2 mmol/l) gave 17 with 62% B2 alleles. 3. The group with low levels of high-density lipoprotein cholesterol had higher activity of cholesteryl ester transfer protein and significantly elevated triacylglycerol levels when compared with the group with high levels of high-density lipoprotein cholesterol. 4. A further significant finding was the correlation of the MspI restriction fragment length polymorphism detected by the apolipoprotein AI gene with lecithin:cholesterol acyltransferase activity.

Adult↗

Acipimox in combination with low dose cholestyramine for the treatment of type II hyperlipidaemia.

1. This study was designed to examine the effects of acipimox 250 mg three times daily and cholestyramine 4 g three times daily on plasma lipids and lipoproteins in 28 hypercholesterolaemic individuals in a prospective double-blind placebo controlled parallel group fashion. 2. Combined treatment with the two agents produced a mean reduction of 27% in plasma total cholesterol and a 32% fall in LDL cholesterol. Plasma triglyceride was reduced by 13% due to a 38% decrement in VLDL cholesterol. 3. In comparison treatment with cholestyramine alone resulted in a 12% fall in plasma cholesterol and a 15% fall in LDL cholesterol. In this group triglycerides and VLDL showed no significant change. 4. Studies of HDL subfraction mass showed that the addition of acipimox to resin therapy produced a mean increment of 45% in HDL2. 5. These results demonstrate the effectiveness of such a well tolerated low dosage combination therapy.

Cholesterol↗

Practice of breast self-examination and the treatment of primary breast cancer.

Past experience of breast self-examination (BSE), family history of breast cancer, method of detection of the tumour, tumour size, node status, tumour attachment and type of treatment used for primary breast cancer, were surveyed on a sample of 117 female breast cancer patients diagnosed in Tasmania during May 1986-June 1987. Family history of breast cancer was associated with higher levels of BSE practice. Three-monthly or more frequent BSE in the year prior to diagnosis was associated with smaller tumours at presentation and less axillary node involvement. Breast-conserving surgery was utilized in 38% of all cases treated, and 84% of these patients received radiotherapy as part of primary treatment.

Adult↗