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Biomedical subjects

A Cassidy

Publications and source records attributed to A Cassidy.

At least 19 recordsLinked to original sources
PubMed2000

Drug-mediated toxicity caused by genetic deficiency of UDP-glucuronosyltransferases.

Human gene families encoding UDP-Glucuronosyltransferases (UGTs) have been identified and partially characterised. This family of enzymes catalysed the glucuronidation of drugs, xenobiotics and endobiotics. Genetic mutations and polymorphisms have been identified in several UGT genes and examples should be anticipated in all UGT genes. A common genetic defect in the TATA box promoter of the UGT1A1 gene is associated with Gilbert's Syndrome (GS) causing mild hyperbilirubinaemia. Recently, adverse effects of anticancer agents have been observed in Gilbert's patients due to reduced drug or bilirubin glucuronidation.

Antineoplastic Agents↗
PubMed2000

Phyto-oestrogens through the life cycle.

The growing interest in the role of phyto-oestrogens in human health has prompted scientists to evaluate the risk : benefit which would result from consuming high levels of these compounds at different stages of the life cycle. These compounds have been shown to exert a wide range of hormonal and non-hormonal activities in animals and in vitro, and these activities suggest plausible mechanisms for potential health effects in human subjects consuming phyto-oestrogen-rich diets. In addition, experimental and epidemiological data are available supporting the concept that phyto-oestrogen-rich diets exert physiological effects in vivo; however, their relative importance to human health remains to be elucidated. Our understanding of factors involved in their absorption and metabolism, including the role of intestinal microflora, is limited, and these factors together with dose-related effects may well be important in determining clinical efficacy.

Adult↗
PubMed1999

Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn.

OBJECTIVE: Prolonged neonatal jaundice, beyond day 14 of life, is very common and of concern to the clinician. The aim of this study was to investigate whether a genetic mutation in the bilirubin UGT1A1 gene, which has been associated with Gilbert's syndrome in adults, is a contributory factor in prolonged neonatal jaundice. STUDY DESIGN: Blood was collected from 85 term newborns with unexplained hyperbilirubinemia, and DNA was prepared. The neonates were divided into 6 groups depending on whether they were breast-fed or bottle-fed and whether they had acute, prolonged, or very prolonged jaundice. UGT1A1 TATA promoter genotyping (DNA test for Gilbert's syndrome) was performed on all samples, and analysis of the entire UGT1A1 coding sequence was performed in a representative sample (11 of 26) of very prolonged cases. RESULTS: In addition to the known common UGT1A1 TATA alleles (TA6 and TA7), a novel TATA allele (TA5) in a neonate with very prolonged jaundice was identified. Statistical analysis of the TATA genotype distributions within the group of breast-fed neonates revealed significant differences among the acute, prolonged, and very prolonged subgroups (.05 > P >.01): the incidence of familial hyperbilirubinemia genotypes (7/7 and 5/7) is 5 times greater in very prolonged cases (31%) relative to acute cases (6%). Neonates with prolonged jaundice from family pedigrees were observed to demonstrate the Gilbert's phenotype as children or young adults. CONCLUSIONS: A genetic predisposition to develop prolonged neonatal hyperbilirubinemia in breast-fed infants is associated with TATA box polymorphism of the UGT1A1 gene and will be recognized as Gilbert's syndrome in adulthood.

Adolescent↗
PubMed1999

Phyto-oestrogens: a potential role in the prevention of CHD?

CHD is a major cause of morbidity and mortality in women. The incidence of CHD in premenopausal women is low but increases substantially after the menopause, and this difference suggests that endogenous oestrogens are cardioprotective. Observational prospective studies have consistently shown that exogenous oestrogens also lower CHD risk. The biological mechanisms by which endogenous and exogenous oestrogens exert their protective effect are multifactorial, affecting lipids, carbohydrate metabolism, body fat distribution and blood pressure. The prevention of CHD with oestrogen therapy is therefore aimed both at correction of the traditional risk factors and at direct control of vessel structure and function. The wide international variation in rates of CHD together with the lower mortality in sub-groups of the population suggests that a considerable proportion of CHD may be prevented by dietary modification. Since phyto-oestrogens are structually similar to oestrogen, they have the potential to mimic its effects in vivo. The hypocholesterolaemic effects of soyabean protein (rich in phyto-oestrogen precursors) are well established, but the underlying mechanism and atherogenic potential of these changes are unknown. One isoflavone, genistein, has been shown in vitro to exert effects which may slow the development of atherosclerotic disease. However, further studies are required to determine the dose-related changes induced by phyto-oestrogens on serum lipoproteins, haemostasis and vascular function.

Coronary Disease↗
PubMed1999

Dietary isoflavones: biological effects and relevance to human health.

Substantial evidence indicates that diets high in plant-based foods may explain the epidemiologic variance of many hormone-dependent diseases that are a major cause of mortality and morbidity in Western populations. There is now an increased awareness that plants contain many phytoprotectants. Lignans and isoflavones represent two of the main classes of phytoestrogens of current interest in clinical nutrition. Although ubiquitous in their occurrence in the plant kingdom, these bioactive nonnutrients are found in particularly high concentrations in flaxseeds and soybeans and have been found to have a wide range of hormonal and nonhormonal activities that serve to provide plausible mechanisms for the potential health benefits of diets rich in phytoestrogens. Data from animal and in vitro studies provide convincing evidence for the potential of phytoestrogens in influencing hormone-dependent states; although the clinical application of diets rich in these estrogen mimics is in its infancy, data from preliminary studies suggest beneficial effects of importance to health. This review focuses on the more recent studies pertinent to this field and includes, where appropriate, the landmark and historical literature that has led to the exponential increase in interest in phytoestrogens from a clinical nutrition perspective.

Cardiovascular Diseases↗
PubMed1999

Potential tissue selectivity of dietary phytoestrogens and estrogens.

The recent discovery of a second estrogen receptor subtype, estrogen receptor-beta, may significantly advance our understanding of tissue specific effects of estrogenic compounds, both natural and synthetic. Although specific effects mediated by estrogen receptor beta in vivo remain to be elucidated, hypothetically the existence of two estrogen receptor subtypes (differing in both tissue distribution and biological activity) may help to explain the curious pharmacological behaviour of many estrogenic and antiestrogenic compounds, including the naturally occurring dietary phytoestrogens.

Animals↗
PubMed1997

Genetic defects of the UDP-glucuronosyltransferase-1 (UGT1) gene that cause familial non-haemolytic unconjugated hyperbilirubinaemias.

Congenital familial non-haemolytic hyperbilirubinaemias are potentially lethal syndromes caused by genetic lesions that reduce or abolish hepatic bilirubin UDP-glucuronosyltransferase activity. Here we describe genetic defects that occur in the UGT1 gene complex that cause three non-haemolytic unconjugated hyperbilirubinaemia syndromes. The most severe syndrome, termed Crigler-Najjar syndrome type I, is mainly associated with mutations in exons 2 to 5 that affect all UGT1 enzymes and many of the mutations result in termination codons and frameshifts. Crigler-Najjar type II syndrome which is treatable with phenobarbital therapy is associated with less dramatic missense mutations or heterozygous expression of mutant and normal alleles. Gilbert's syndrome, the most prevalent (2-19% in population studies) and mildest of the three syndromes is principally caused by a TA insertion at the TATA promoter region upstream of the UGT1A1 exon. Current methods used for the diagnosis and treatment of these diseases are discussed.

Crigler-Najjar Syndrome↗
PubMed1997

Validation of dietary assessment methods in the UK arm of EPIC using weighed records, and 24-hour urinary nitrogen and potassium and serum vitamin C and carotenoids as biomarkers.

BACKGROUND: In the UK EPIC validation studies, the accuracy of several methods was assessed by comparison with to-day weighed records and the biomarkers, 24-hour urine nitrogen (N) and potassium (K), plasma carotenoids and plasma vitamin C. METHODS: Comparisons between methods were made on 156 women, studied over 1 year at 3-monthly intervals at home. On each of four occasions, volunteers completed 4 days of weighed records and provided two 24-hour urine collections and a fasting blood sample. RESULTS: In comparison with the 16 days of weighed records, a food frequency questionnaire (FFQ) yielded higher values mainly due to greater reported consumption of milk and of vegetables. A 24-hour recall was as good as the FFQ in placing individuals in the distribution of habitual diet from weighed records. Results obtained from a 7-day estimated record were closest to those obtained from the weighed record. Correlations between 24-hour urine excretion and dietary N intake from weighed records were high (0.78-0.87) as were those with estimated food diaries (0.60-0.70). Correlations between urine N and the FFQ and 24-hour recall were lower (0.10 to 0.27), but improved by energy adjustment using residuals for N and K which are correlated with total energy intake. Comparisons between dietary estimates and urinary K and serum carotenoids and vitamin C showed broadly similar results. Limited biomarker information amongst 200 UK EPIC participants supported the findings of the validation study. CONCLUSIONS: UK EPIC uses three methods (the 7-day diary, an improved FFQ, and the 24-hour recall) to assess diet. 93% of first food diaries are returned completed by participants. Repeated diaries are the main dietary assessment method for nested case-control analyses.

Aged↗
PubMed1996

Using nursing theory to introduce change in practice.

This article outlines the theoretical basis of nursing using Carper's (1978) fundamental patterns of knowing and explains how this theory can be integrated with practice. The authors also describe how Carper's theory was used to introduce change related to the reduction in junior doctors' hours through the development, implementation and evaluation of nurse practitioners. Using a SWOT analysis exercise and various workshops, practitioners have been able to develop professionally and integrate the art and science of nursing.

Education, Nursing, Continuing↗
PubMed1996

Depletion of brain glutathione results in a decrease of glutathione reductase activity; an enzyme susceptible to oxidative damage.

Loss of the intracellular antioxidant glutathione (GSH) from the substantia nigra is considered to be an early event in the pathogenesis of Parkinson's disease (PD). While the cause of the loss is unclear, an imbalance in the enzymes associated with the synthesis, utilisation, degradation and translocation of GSH has been implicated. The enzyme glutathione reductase is also important in GSH homeostasis: it regenerates GSH from the oxidised from (GSSG). However, to date the activity and regulation of glutathione reductase in conditions such as PD have not been explored. In view of this we have measured the effects of GSH depletion on glutathione reductase activity of the rat brain. Other glutathione related enzymes were also measured. Using pre-weanling rats, brain GSH was depleted by up to 60% by subcutaneous administration of L-buthionine sulfoximine. The only enzyme affected by GSH depletion was glutathione reductase; its activity being reduced by approximately 40%. As GSH inactivates a number of oxidising species including peroxynitrite (ONOO-), we additionally investigated the susceptibility of glutathione reductase to ONOO- in vitro, using purified enzyme. ONOO- decreased glutathione reductase activity in a concentration dependent manner with an apparent 50% inhibition occurring at an initial concentration of 0.09 mM. These data suggest that GSH is important in the maintenance glutathione reductase activity. This may arise in part from its ability to inactivate oxidising agents such as ONOO-.

Animals↗
PubMed1995

Validation of weighed records and other methods of dietary assessment using the 24 h urine nitrogen technique and other biological markers.

Results from analysis of 24 h urine collections, verified for completeness with para-amino benzoic acid, and blood samples collected over 1 year were compared with 16 d weighed records of all food consumed collected over the year, and with results from 24 h recalls, food-frequency questionnaires and estimated food records in 160 women. Using the weighed records, individuals were sorted into quintiles of the distribution of the urine N excretion:dietary N intake ratio (UN:DN). UN exceeded DN in the top quintile of this ratio; mean ratio UN:DN = 1.13. Individuals in this top quintile were heavier, had significantly greater body mass indices, were reportedly more restrained eaters, had significantly lower energy intake:basal metabolic rate ratios (EI:BMR), and had correlated ratios of UN:DN and EI:BMR (r -0.62). Those in the top quintile reported lower intakes of energy and energy-yielding nutrients, Ca, fats, cakes, breakfast cereals, milk and sugars than individuals in the other quintiles but not lower intakes of non-starch polysaccharides, vitamin C, vegetables, potatoes or meat. Correlations between dietary intake from weighed records and 24 h urine K were 0.74 and 0.82, and between dietary vitamin C and beta-carotene and plasma vitamin C and beta-carotene 0.86 and 0.48. Correlations between dietary N intake from weighed records and 24 h urine excretion were high (0.78-0.87). Those between N from estimated food records and urine N were r 0.60-0.70. Correlations between urine N and 24 h recalls and food-frequency questionnaires were in the order of 0.01 to 0.5. Despite problems of underreporting in overweight individuals in 20% of this sample, weighed records remained the most accurate method of dietary assessment, and only an estimated 7 d diary was able to approach this accuracy.

Basal Metabolism↗
PubMed1995

Biological effects of isoflavones in young women: importance of the chemical composition of soyabean products.

To examine the hormonal effects of isoflavones, of which soyabean is a rich source, fifteen healthy nonvegetarian premenopausal women were studied over 9 months. They lived in a metabolic suite for between 4 and 6 months where their diet and activity levels were kept constant and their hormonal status was measured over two or three menstrual cycles. During one (control) menstrual cycle a normal but constant diet containing no soyabean products was fed. Then, over a second complete cycle six subjects consumed a similar diet into which 60 g textured vegetable protein (TVP)/d, containing 45 mg conjugated isoflavones, had been incorporated. Three participants had 50 g miso (a fermented soyabean paste), containing 25 mg unconjugated isoflavones, added daily to their diet over a menstrual cycle, and six others consumed 28 g TVP/d, containing 23 mg conjugated isoflavones. Five participants completed a third diet period where they were randomly assigned to consume either the control diet over a cycle, or a similar diet incorporating 60 g of a soyabean product which had had the isoflavones chemically extracted (Arcon F). Follicular phase length was significantly (P < 0.01) increased and peak progesterone concentrations were delayed with 60 g TVP but no effects were observed with Arcon F. The increase in menstrual cycle length did not reach statistical significance in the three three subject who ate 50 g miso/d, but peak progesterone levels were significantly (P < 0.05) delayed. Mid-cycle peaks of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were suppressed with 45 mg conjugated isoflavones as 60 g TVP (P < 0.05 and P < 0.01 respectively). No other changes in sex-steroid hormone levels were observed on any of the other diets. A significant reduction in total cholesterol was found with 45 mg conjugated isoflavones (P < 0.05), but not with 23 mg conjugated isoflavone-free Arcon F. There was no effect of menstrual cycle phase on transit time.

Adult↗
PubMed1994

Starch intake and colorectal cancer risk: an international comparison.

Intakes of starch, non-starch polysaccharides (NSPs), protein and fat have been compared with colorectal cancer incidence in 12 populations worldwide. There were strong inverse associations between starch consumption and large bowel cancer incidence (large bowel r = -0.70, colon r = -0.76). There was no significant relation with NSPs, although the association with large bowel cancer incidence was still significant when NSP was combined with resistant starch (RS) to give an estimate of fermentable carbohydrate (large bowel r = -0.52, colon r = -0.60). The relationships between starch, RS and NSPs and cancer incidence remained statistically significant after adjusting for fat and protein intakes. The strong inverse associations found here suggest a potentially important role for starch in protection against colorectal cancer and correspond with the hypothesis that fermentation in the colon is the mechanism for preventing colorectal cancer. Measures of both starch and NSPs need to be included in future epidemiological studies of diet and bowel cancer.

Age Factors↗
PubMed1994

Comparison of dietary assessment methods in nutritional epidemiology: weighed records v. 24 h recalls, food-frequency questionnaires and estimated-diet records.

Women (n 160) aged 50 to 65 years were asked to weigh their food for 4 d on four occasions over the period of 1 year, using the PETRA (Portable Electronic Tape Recorded Automatic) scales. Throughout the year, they were asked to complete seven other dietary assessment methods: a simple 24 h recall, a structured 24 h recall with portion size assessments using photographs, two food-frequency questionnaires, a 7 d estimated record or open-ended food diary, a structured food-frequency (menu) record, and a structured food-frequency (menu) record with portion sizes assessed using photographs. Comparisons between the average of the 16 d weighed records and the first presentation of each method indicated that food-frequency questionnaires were not appreciably better at placing individuals in the distribution of habitual diet than 24 h recalls, due partly to inaccuracies in the estimation of frequency of food consumption. With a 7 d estimated record or open-ended food diary, however, individual values of nutrients were most closely associated with those obtained from 16 d weighed records, and there were no significant differences in average food or nutrient intakes.

Diet Records↗
PubMed1994

Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women.

The influence of a diet containing soy protein on the hormonal status and regulation of the menstrual cycle was examined in six premenopausal women with regular ovulatory cycles. Soy protein (60 g containing 45 mg isoflavones) given daily for 1 mo significantly (P < 0.01) increased follicular phase length and/or delayed menstruation. Midcycle surges of luteinizing hormone and follicle-stimulating hormone were significantly suppressed during dietary intervention with soy protein. Plasma estradiol concentrations increased in the follicular phase and cholesterol concentrations decreased 9.6%. Similar responses occur with tamoxifen, an antiestrogen undergoing clinical trial as a prophylactic agent in women at high risk for breast cancer. These effects are presumed to be due to nonsteroidal estrogens of the isoflavone class, which behave as partial estrogen agonists/antagonists. The responses to soy protein are potentially beneficial with respect to risk factors for breast cancer and may in part explain the low incidence of breast cancer and its correlation with a high soy intake in Japanese and Chinese women.

Adult↗
PubMed1993

Sex hormones and bone mineral density in elderly men.

The aim of this study was to determine the relationships between sex hormones and bone mineral density (BMD) in older men. Community-dwelling men (n = 134, mean age (SD) 69.5 (3.1) years) were recruited from two general practices in Cambridge, UK. Plasma total testosterone and sex hormone binding globulin (SHBG) were assayed and a free androgen index (FAI) was derived as the ratio of total testosterone to SHBG (x 100). Spine and hip BMD were measured by dual energy x-ray absorptiometry using the Hologic QDR-1000. After adjusting for age and body mass index (BMI), the FAI correlated with femoral neck (r = 0.20, P = 0 0.03), intertrochanteric, trochanteric and Ward's Triangle BMD (r = 0.22, P = 0.01). Analysis of variance, with adjustment for age and BMI, showed a progressive upward trend of hip BMD with increasing quartiles of FAI. The findings suggest that free testosterone plays a role in determining bone mineral density in older men.

Absorptiometry, Photon↗