Biomedical subjects

N Day

Publications and source records attributed to N Day.

At least 19 recordsLinked to original sources

PubMed2006

In vitro-clinical correlations for amphotericin B susceptibility in AIDS-associated cryptococcal meningitis.

Reliable measures of antifungal drug susceptibility are needed. We tested the susceptibility of Cryptococcus neoformans from patients treated with amphotericin B. In vitro susceptibility employed a modified broth macrodilution method. We demonstrate a strong correlation between the quantitative measures of in vitro amphotericin B susceptibility and the quantitative response observed in patients.

AIDS-Related Opportunistic Infections↗

PubMed2005

Minor physical anomalies are not increased in the offspring of mothers with systemic lupus erythematosus.

OBJECTIVE: To determine the incidence and type of minor physical anomalies (MPAs) in infants born to mothers with systemic lupus erythematosus (SLE). METHODS: Each trimester, pregnant women with SLE were assessed for disease activity, prescribed drug use, and exposure to tobacco, alcohol, and illicit drugs through a self reported questionnaire. Infant examinations were performed on 30/39 (77%) live births in women with SLE and the incidence of MPAs determined. RESULTS: 2/30 (7%) patients had three or more MPAs; 4 (13%) had two; 7 (23%) had one; and 17 (57%) had none. One in three women reported alcohol, tobacco, and illicit drug use. Facial anomalies were the most common MPAs. The relative risk and 95% confidence interval for any MPA were 2.05 (0.99 to 4.26) for tobacco use; 1.95 (0.92 to 4.11) for alcohol use; 1.36 (0.165 to 11.23) for maternal disease flare; 0.63 (0.27 to 1.47) for prednisone use; and 0.72 (0.21 to 2.44) for aspirin use. CONCLUSION: 13/30 (43%) infants had minor anomalies-a similar incidence to that of the general population. Counselling for preventable self reported exposure is advisable in addition to counselling specifically for lupus management during pregnancy.

Acute Disease↗

PubMed2005

Development and validation of a bioanalytical method using automated solid-phase extraction and LC-UV for the simultaneous determination of lumefantrine and its desbutyl metabolite in plasma.

A bioanalytical method for the determination of lumefantrine (LF) and its metabolite desbutyl-lumefantrine (DLF) in plasma by solid-phase extraction (SPE) and liquid chromatography has been developed. Plasma proteins were precipitated with acetonitrile:acetic acid (99:1, v/v) containing a DLF analogue internal standard before being loaded onto a octylsilica (3 M Empore) SPE column. Two different DLF analogues were evaluated as internal standards. The compounds were analysed by liquid chromatography UV detection on a SB-CN (250 mm x 4.6 mm) column with a mobile phase containing acetonitrile-sodium phosphate buffer pH (2.0; 0.1 M) (55:45, v/v) and sodium perchlorate 0.05 M. Different SPE columns were evaluated during method development to optimise reproducibility and recovery for LF, DLF and the two different DLF analogues. The within-day precisions for LF were 6.6 and 2.1% at 0.042 and 8.02 microg/mL, respectively, and for DLF 4.5 and 1.5% at 0.039 and 0.777 microg/mL, respectively. The between-day precisions for LF were 12.0 and 2.9% at 0.042 and 8.02 microg/mL, respectively, while for DLF 0.7 and 1.2% at 0.039 and 0.777 microg/mL, respectively. The limit of quantification was 0.024 and 0.021 microg/mL for LF and DLF, respectively. Different amounts of lipids in plasma did not affect the absolute recovery of LF or DLF.

Chromatography, Liquid↗

PubMed2005

The effects of acclimation to reversed seasonal temperatures on the swimming performance of adult brown trout Salmo trutta.

Adult brown trout (Salmo trutta) were acclimatised to and maintained at seasonal temperatures (5 degrees C in winter; 15 degrees C in summer) and acclimated to reversed seasonal temperatures (15 degrees C in winter; 5 degrees C in summer) while exposed to the natural (i.e. seasonally variable) photoperiod. The mean critical swimming speeds (U(crit)) of animals acclimatised to the seasonal temperatures were similar, but more than 30% greater than those for fish acclimated to the reversed seasonal temperatures. The lower values of U(crit) that accompanied acclimation to reversed seasonal temperatures appeared largely to result from the inability of white muscle to function maximally, since the concentrations of lactate and ammonia in white muscle of fish swum to U(crit) at reversed seasonal temperatures were significantly lower than those in fish swum at seasonal temperatures. These observations, together with biochemical and morphometric attributes of muscle tissue, suggest that swimming ability is influenced, at least in part, by seasonal factors other than temperature. These data have important implications for the design of experiments using fish that experience predictable, usually seasonal, changes in their natural environment (temperature, dissolved oxygen, changes in water levels, etc.).

Acclimatization↗

PubMed2004

Abdominal obesity and respiratory function in men and women in the EPIC-Norfolk Study, United Kingdom.

Poor respiratory function and obesity are associated with all-cause and cardiovascular disease mortality. Obese persons may also have impaired lung function, but the mechanism is unclear. The authors investigated the relation between abdominal pattern of obesity and respiratory function in the European Prospective Investigation into Cancer and Nutrition-Norfolk (EPIC-Norfolk) cohort in Norfolk, United Kingdom. This analysis included 9,674 men and 11,876 women aged 45-79 years with no known preexisting serious illness who had complete anthropometric and respiratory function measures obtained at a health visit between 1993 and 1997. Waist:hip ratio was used to assess abdominal obesity, and forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), obtained by spirometry, were used to assess respiratory function. Both FEV1 and FVC were linearly and inversely related across the entire range of waist:hip ratio in both men and women. This relation persisted after adjustment for age, body mass index, cigarette smoking, social class, physical activity index, prevalent bronchitis/emphysema, and prevalent asthma. The association remained significant among nonobese nonsmokers without preexisting respiratory disease. In the general adult population, abdominal fat deposition may play a role in the impairment of respiratory function among the abdominally obese.

Abdomen↗

PubMed2004

Traditional cardiovascular risk factors measured prior to the onset of inflammatory polyarthritis.

BACKGROUND: Cardiovascular mortality is increased in patients with seropositive inflammatory polyarthritis (IP). We tested the hypothesis that the increased risk of cardiovascular disease (CVD) can be explained by elevated traditional CVD risk factor levels in persons prior to development of IP. METHODS: In a population-based, prospective nested case-control study, 25 600 people aged 45-75 yr participated in a health survey, including standard CVD risk factor assessment, between the years 1993 and 1997. There were 91 incident IP cases (one-third were seropositive at presentation) identified during follow-up to the end of July 2001. Baseline CVD risk factors in the IP cases were compared with those in two age/gender-matched controls. RESULTS: Current smokers had an odds ratio of 2.0 (95% CI 1.0-4.0) for IP. Other risk factors, including total and LDL cholesterol, systolic and diastolic blood pressure and obesity, did not differ significantly between cases and controls. Importantly, in combination, using a standard coronary disease risk score, these factors only had a modest association with future IP, and no association when analysis was restricted to the smaller number of cases who were seropositive. CONCLUSION: Of the traditional cardiovascular risk factors, only smoking increases CVD risk prior to the onset of IP. Therefore the increased CVD observed in these patients is likely to be a consequence of factors operating after the onset of the arthritis.

Aged↗

PubMed2004

Occupational social class, educational level and area deprivation independently predict plasma ascorbic acid concentration: a cross-sectional population based study in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk).

OBJECTIVE: To investigate the independent association between three different measures of socioeconomic status and plasma ascorbic acid level. DESIGN: Cross-sectional population based study. SETTING AND PARTICIPANTS: 20 292 men and women aged 39-79 y who participated in the EPIC-Norfolk study. RESULTS: Individuals in manual social classes, who had no educational qualifications or those who lived in the most deprived areas had significantly lower levels of plasma ascorbic acid compared to those in nonmanual social classes, with at least O-level qualifications or who lived in less deprived areas. The magnitude of effect for each measure of socioeconomic status was greater in current smokers compared to current nonsmokers. CONCLUSION: Education and social class were stronger predictors of differences in ascorbic acid levels, an indicator of dietary health behaviour, than a deprivation index based on the Townsend score. This suggests that education could be particularly important in influencing large socioeconomic differentials in health related behaviours and potentially, health outcomes in the UK.

Adult↗

PubMed2004

Vitamin C and the risk of developing inflammatory polyarthritis: prospective nested case-control study.

OBJECTIVE: To investigate whether, there is an association between consumption of fruit and vegetables and dietary antioxidants and the risk of developing inflammatory polyarthritis (IP). METHODS: In a prospective, population based, nested case-control study of residents of Norfolk, UK, men and women aged 45-74 years were recruited, between 1993 and 1997 through general practice age-sex registers to the Norfolk arm of the European Prospective Investigation of Cancer (EPIC-Norfolk). Dietary intake was assessed at baseline using 7 day diet diaries. Seventy three participants who went on to develop IP between 1993 and 2001 and were registered by the Norfolk Arthritis Register (NOAR) were identified. Incident cases of IP, assessed by general practitioners, fulfilled the criteria of two or more swollen joints, persisting for a minimum of 4 weeks. Each case of IP was matched for age and sex with two controls free of IP. RESULTS: Lower intakes of fruit and vegetables, and vitamin C were associated with an increased risk of developing IP. Those in the lowest category of vitamin C intake, compared with the highest, increased their risk of developing IP more than threefold, adjusted odds ratio (OR) with 95% confidence intervals (CI) 3.3 (95% CI 1.4 to 7.9). Weak inverse associations between vitamin E and beta-carotene intake and IP risk were found. CONCLUSION: Patients with IP (cases) consumed less fruit and vitamin C than matched controls, which appeared to increase their risk of developing IP. The mechanism for this effect is uncertain. Thus similar studies are necessary to confirm these results.

Aged↗

PubMed2004

Area deprivation predicts lung function independently of education and social class.

The cross-sectional association between socioeconomic status (at both the individual and area-based level) and lung function, as measured by forced expiratory volume in one second, in a large population-based cohort was investigated. The study population consisted of 22,675 males and females aged 39-79 yrs. They were recruited from the general community in Norfolk, UK using general practice age/sex registers, as part of the European Prospective Investigation into Cancer (EPIC-Norfolk). It was found that being in a manual occupational social class, having no educational qualifications and living in a deprived area all independently predicted significantly lower lung function, even after controlling for smoking habit. The influence of area-deprivation on lung function, independent of individual socioeconomic status and of individual smoking habit, suggests that apart from targeting individuals who are at high-risk, such as smokers, environmental determinants also need to be examined when considering measures to improve respiratory health.

Adult↗

PubMed2003

Vitamin K and childhood cancer: a report from the United Kingdom Childhood Cancer Study.

The relationship between neonatal vitamin K received by the intramuscular (i.m.) route and the development of leukaemia or other cancers was investigated as part of a national case-control study of childhood cancer, using data abstracted from obstetric and neonatal records. The analyses included 2530 children diagnosed with cancer before 15 years of age, 1174 of whom had leukaemia and 4487 control children without cancer. Overall, 39% of cases and 42% of controls had records of i.m. vitamin K administration, while 24% of cases and 22% of controls had no record of whether or not they had received vitamin K. Using subjects who received i.m. vitamin K as the baseline group, our analyses found no association between the administration of i.m. vitamin K and either leukaemia or other cancers as a group. We conclude that there is no convincing evidence that neonatal vitamin K administration, irrespective of the route by which it is given, influences the risk of children developing leukaemia or any other cancer.

Adolescent↗

PubMed2003

Residential area deprivation predicts smoking habit independently of individual educational level and occupational social class. A cross sectional study in the Norfolk cohort of the European Investigation into Cancer (EPIC-Norfolk).

OBJECTIVES: To investigate the independent association between individual and area based measures of socioeconomic status and cigarette smoking habit. DESIGN AND SETTING: Cross sectional, population based study. PARTICIPANTS AND METHODS: 12 579 men and 15 132 women aged 39-79 years living in the general community participating in the EPIC-Norfolk Study in 1993-1997. The association between social class, educational status, Townsend residential deprivation level, and cigarette smoking status was examined. MAIN OUTCOME MEASURES: Cigarette smoking status at baseline survey. RESULTS: Social class, educational level, and residential deprivation level independently related to cigarette smoking habit in both men and women. Multivariate age adjusted odds ratios for current smoking in men were 1.62 (95% CI 1.45 to 1.81) for manual compared with non-manual social class, 1.32 (95% CI 1.17 to 1.48) for those with educational level less than O level compared with those with O level qualifications or higher and 1.84 (95% CI 1.62 to 2.08) for high versus low area deprivation level. For women, the odds ratios for current smoking for manual social class were 1.14 (95% CI 1.03 to 1.27); 1.31 (95% CI 1.18 to 1.46) for low educational level and 1.68 (95% CI 1.49 to 1.90) for high residential deprivation respectively. CONCLUSIONS: Residential deprivation level using the Townsend score, individual social class, and educational level all independently predict smoking habit in both men and women. Efforts to reduce cigarette smoking need to tackle not just individual but also area based factors. Understanding the specific factors in deprived areas that influence smoking habit may help inform preventive efforts.

Adult↗

PubMed2002

5-HT(2B) receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro.

1. 5-Hydroxytryptamine (5-HT) is known to produce a number of different effects in the gastrointestinal tract of various species, and has been proposed to play a key role in a number of intestinal disorders in man, including irritable bowel syndrome (IBS), although the receptors involved have yet to be established. The aim of the present study was to investigate the distribution and function of 5-HT(2B) receptors in human colon, and to establish their possible role in the aetiology of IBS. 2. The distribution of 5-HT(2B) receptor mRNA and protein were investigated by quantitative RT - PCR, Western analysis and immunocytochemistry. High levels of both mRNA and protein for 5-HT(2B) receptors were found throughout the human gastrointestinal tract, and in particular in colon, where 5-HT(2B) receptors were found predominantly in the longitudinal and circular smooth muscle layers within the muscularis externa, and in the myenteric nerve plexus lying between these two layers. 3. Electrical field stimulation of longitudinal muscle preparations of human colon mounted in organ baths resulted in neuronally-mediated contractile responses, that were significantly potentiated by application of 5-HT (up to 10(-7) M), with a pEC(50) of 8.2 +/- 0.1 (n=49 donors). The response to 5-HT was inhibited by a number of selective 5-HT(2B) receptor antagonists. 4. This study has shown for the first time that, in contrast to animal studies, the excitatory effects of 5-HT in human colon are mediated by 5-HT(2B) receptors. It is proposed that these receptors contribute to the putative 5-HT-induced colonic smooth muscle hypersensitivity associated with IBS.

Colon↗

PubMed2001

Frequency of eating and concentrations of serum cholesterol in the Norfolk population of the European prospective investigation into cancer (EPIC-Norfolk): cross sectional study.

OBJECTIVES: To examine the relation between self reported eating frequency and serum lipid concentrations in a free living population. DESIGN: Cross sectional population based study. SETTING: Norfolk, England. PARTICIPANTS: 14 666 men and women aged 45-75 years from the Norfolk cohort of the European prospective investigation into cancer (EPIC-Norfolk). MAIN OUTCOME MEASURES: Concentrations of blood lipids. RESULTS: Mean concentrations of total cholesterol and low density lipoprotein cholesterol decreased in a continuous relation with increasing daily frequency of eating in men and women. No consistent relation was observed for high density lipoprotein cholesterol, body mass index, waist to hip ratio, or blood pressure. Mean cholesterol concentrations differed by about 0.25 mmol/l between people eating more than six times a day and those eating once or twice daily; this difference was reduced to 0.15 mmol/l after adjustment for possible confounding variables, including age, obesity, cigarette smoking, physical activity, and intake of energy and nutrients (alcohol, fat, fatty acids, protein, and carbohydrate). CONCLUSIONS: Concentrations of total cholesterol and low density lipoprotein cholesterol are negatively and consistently associated with frequency of eating in a general population. The effects of eating frequency on lipid concentrations induced in short term trials in animals and human volunteers under controlled laboratory conditions can be observed in a free living general population. We need to consider not just what we eat but how often we eat.

Aged↗

PubMed2001

Protein kinase Calpha plays a critical role in mannosylerythritol lipid-induced differentiation of melanoma B16 cells.

Mannosylerythritol lipid (MEL), a novel extracellular glycolipid from yeast, was found to inhibit the proliferation of mouse melanoma B16 cells in a dose-dependent manner and to induce the apoptosis of B16 cells at concentrations higher than 10 microm (Zhao, X., Wakamatsu, Y., Shibahara, M., Nomura, N., Geltinger, C., Nakahara, T., Murata, T., and Yokoyama, K. K. (1999) Cancer Res. 59, 482-486). We show here that exposure of B16 cells to MEL (5 microm) for 2 days resulted in an increase of the levels of differentiation-associated markers of melanoma cells such as melanogenesis and tyrosinase activity, which were accompanied by morphological changes. The MEL-induced differentiation of B16 cells at this concentration was closely associated with arrest of the cell cycle at G(1) phase, but no significant population of apoptotic cells was identified. Expression of protein kinase Calpha (PKCalpha) was enhanced after exposure of B16 cells to MEL for 48 h. Antisense oligodeoxynucleotides against the mouse gene for PKCalpha prevented MEL-induced melanogenesis in B16 cells. Conversely, the effects of the expression of a constitutively active form of PKCalpha mimicked the effects of MEL on B16 cells. These data suggest that MEL, a yeast-derived glycolipid, triggers the differentiation of B16 melanoma cells through a signaling pathway that involves PKCalpha.

Animals↗

PubMed2001

Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Ascorbic acid (vitamin C) might be protective for several chronic diseases. However, findings from prospective studies that relate ascorbic acid to cardiovascular disease or cancer are not consistent. We aimed to assess the relation between plasma ascorbic acid and subsequent mortality due to all causes, cardiovascular disease, ischaemic heart disease, and cancer. METHODS: We prospectively examined for 4 years the relation between plasma ascorbic acid concentrations and mortality due to all causes, and to cardiovascular disease, ischaemic heart disease, and cancer in 19 496 men and women aged 45-79 years. We recruited individuals by post using age-sex registers of general practices. Participants completed a health and lifestyle questionnaire and were examined at a clinic visit. They were followed-up for causes of death for about 4 years. Individuals were divided into sex-specific quintiles of plasma ascorbic acid. We used the Cox proportional hazard model to determine the effect of ascorbic acid and other risk factors on mortality. FINDINGS: Plasma ascorbic acid concentration was inversely related to mortality from all-causes, and from cardiovascular disease, and ischaemic heart disease in men and women. Risk of mortality in the top ascorbic acid quintile was about half the risk in the lowest quintile (p<0.0001). The relation with mortality was continuous through the whole distribution of ascorbic acid concentrations. 20 micromol/L rise in plasma ascorbic acid concentration, equivalent to about 50 g per day increase in fruit and vegetable intake, was associated with about a 20% reduction in risk of all-cause mortality (p<0.0001), independent of age, systolic blood pressure, blood cholesterol, cigarette smoking habit, diabetes, and supplement use. Ascorbic acid was inversely related to cancer mortality in men but not women. INTERPRETATION: Small increases in fruit and vegetable intake of about one serving daily has encouraging prospects for possible prevention of disease.

Age Distribution↗

PubMed2001

Predicted long-term mortality reduction associated with the second round of breast screening in East Anglia.

Randomized trials have demonstrated that mammographic screening can reduce breast cancer mortality. Our aim was to estimate the reduction in mortality expected from the East Anglian Breast Screening Programme. Breast screening achieves benefit by improving cancer prognosis (reducing tumour size, nodal involvement and possibly grade) through earlier diagnosis. We compared cancer prognosis between women invited for screening and those not yet invited in East Anglia, UK, in order to predict the mortality reduction achievable by screening, independently of any reduction due to changes in treatment and underlying disease. Participants (both invited and not-yet invited) were women eligible for invitation to first and second screens and diagnosed with invasive breast cancer in 1989-96. Death rates were predicted based on the observed distribution of tumour grade, size and node status amongst 950 cancers diagnosed following first invitation, up to and including at second screen (excluding those detected at first screening), and 451 cancers presenting symptomatically in women awaiting first invitation during the staggered introduction of screening, after adjustment for lead time amongst screen detected cases. For all ages, the ratio of predicted breast cancer mortality in the invited compared with the uninvited group was 0.85 (95% CI 0.78, 0.93). It was 0.93 (0.80, 1.08) for women aged 50-54 at diagnosis and 0.81 (0.72, 0.91) for those aged 55-64. We conclude that, by 2004, the second round of screening in East Anglia should reduce mortality by around 7% in women below age 55 at diagnosis, and by around 19% in those aged 55-64.

Age Factors↗

PubMed2001

Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospective investigation of cancer and nutrition (EPIC-Norfolk).

OBJECTIVE: To examine the value of glycated haemoglobin (HbA(1c)) concentration, a marker of blood glucose concentration, as a predictor of death from cardiovascular and all causes in men. DESIGN: Prospective population study. SETTING: Norfolk cohort of European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). SUBJECTS: 4662 men aged 45-79 years who had had glycated haemoglobin measured at the baseline survey in 1995-7 who were followed up to December 1999. MAIN OUTCOME MEASURES: Mortality from all causes, cardiovascular disease, ischaemic heart disease, and other causes. RESULTS: Men with known diabetes had increased mortality from all causes, cardiovascular disease, and ischaemic disease (relative risks 2.2, 3.3, and 4.2, respectively, P <0.001 independent of age and other risk factors) compared with men without known diabetes. The increased risk of death among men with diabetes was largely explained by HbA(1c) concentration. HbA(1c) was continuously related to subsequent all cause, cardiovascular, and ischaemic heart disease mortality through the whole population distribution, with lowest rates in those with HbA(1c) concentrations below 5%. An increase of 1% in HbA(1c) was associated with a 28% (P<0.002) increase in risk of death independent of age, blood pressure, serum cholesterol, body mass index, and cigarette smoking habit; this effect remained (relative risk 1.46, P=0.05 adjusted for age and risk factors) after men with known diabetes, a HbA(1c) concentration >/=7%, or history of myocardial infarction or stroke were excluded. 18% of the population excess mortality risk associated with a HbA(1c) concentration >/=5% occurred in men with diabetes, but 82% occurred in men with concentrations of 5%-6.9% (the majority of the population). CONCLUSIONS: Glycated haemoglobin concentration seems to explain most of the excess mortality risk of diabetes in men and to be a continuous risk factor through the whole population distribution. Preventive efforts need to consider not just those with established diabetes but whether it is possible to reduce the population distribution of HbA(1c) through behavioural means.

Aged↗

PubMed2001

Mannosylerythritol lipid induces characteristics of neuronal differentiation in PC12 cells through an ERK-related signal cascade.

Rat pheochromocytoma PC12 cells undergo neuronal differentiation in response to nerve growth factor (NGF). The differentiation involves protein kinase cascades that include the kinases MEK and ERK, as well as activation of the transcription factors c-Jun and c-Fos. We show here, that exposure of PC12 cells to mannosylerythritol lipid (MEL), a yeast extracellular glycolipid, enhances the activity of acetylcholinesterase and interrupts the cell cycle at the G1 phase, with resulting outgrowth of neurites and partial cellular differentiation. Treatment with MEL stimulates the phosphorylation of ERK to a similar extent as treatment with NGF, although, the appearance of phosphorylated ERK is somewhat delayed. Both the MEL-induced outgrowth of neurites and the increase in the activity of acetylcholinesterase are prevented by PD98059, a specific inhibitor of MEK. Northern blotting analysis of c-jun transcripts and analysis of transcription in PC12 cells of a c-jun/CAT reporter construct demonstrated a significant increase in the rate of transcription of the c-jun gene upon treatment with MEL. The sequence elements required for the MEL-mediated activation of transcription of the c-jun gene are located between nucleotides -126 and -79 in the 5' flanking region. Our results suggest that MEL induces characteristics of neuronal differentiation in PC12 cells, with transactivation of the c-jun gene, via an ERK-related signal cascade that is partially overlapping the pathways activated in response to NGF. These results might provide the groundwork for the use of microbial extracellular glycolipids as novel reagents for the treatment of cancer cells.

Acetylcholinesterase↗