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Biomedical subjects

S Bingham

Publications and source records attributed to S Bingham.

At least 73 records · Page 4Linked to original sources
PubMed1996

Vitamin c status and undiagnosed angina.

BACKGROUND: Vitamin C has been suggested to be protective for coronary heart disease but the evidence from epidemiological studies is inconclusive and most studies have been conducted in men. We examined the cross-sectional relationship between vitamin C status and previously undiagnosed angina in women. METHODS: Women aged 45-74 years were recruited from general practices. They completed a health and lifestyle questionnaire and attended for a health check and a blood test. Non-fasting plasma vitamin C was used to define vitamin status and a self-completed Rose angina questionnaire was used to identify cases. RESULTS: Forty-two women with previously undiagnosed angina (cases) were compared with 877 women with no reported angina (controls). The mean plasma vitamin C was 50.2 mumol/l in cases and 58.3 mumol/l in controls. The age-adjusted odds ratio for a 50 mumol/l increase in plasma vitamin C was 0.34 (95% confidence interval 0.15-0.79). The odds ratio was unaltered after adjustment for body mass index, smoking and established coronary risk factors, and after stratification by smoking, vitamin supplementation and hormone replacement. CONCLUSIONS: This cross-sectional analysis showed an association in women between lower plasma levels of vitamin C and previously undiagnosed angina. Although we are unable to exclude the possibility that symptomatic prevalent disease modifies plasma vitamin C levels, these data are consistent with a protective effect of vitamin C for coronary heart disease. This relationship requires confirmation in further prospective studies and trials of vitamin C supplementation.

Aged↗
PubMed1996

Vitamin C status and blood pressure.

OBJECTIVE: To examine the cross-sectional relationship between blood pressure and plasma vitamin C. DESIGN: A cross-sectional analysis. SETTING: A population-based study. SUBJECTS: The subjects were 835 men and 1025 women aged 45-75 years registered with general practices in Norfolk. INTERVENTIONS: Completion of health and lifestyle questionnaire and attendance for a health check. MAIN OUTCOME MEASURES: Diastolic blood pressure (DBP), systolic blood pressure (SBP) and plasma vitamin C level. RESULTS: The mean SBP was 135.8 +/- 18.5 mmHg (mean +/- SD) and the mean DBP was 82.5 +/- 11.3 mmHg. The mean plasma vitamin C level was 52.6 +/- 19.7 mumol/l. The plasma vitamin C level was negatively correlated both with SBP and with DBP. These correlations persisted after adjustment for age, sex and body mass index. Adjusting for other confounders including cigarette smoking, physical activity and alcohol intake did not alter the observed association. Exclusion of subjects taking vitamin supplements and those with known hypertension did not affect the results. The differences in SBP and in DBP for a 50 mumol/l difference in vitamin C, estimated using linear regression, were -3.6 and -2.6 mmHg, respectively. CONCLUSIONS: The plasma vitamin C level may be a marker of other factors; nevertheless, these results are consistent with other published work indicating that a high intake of vitamin C from food confers protection against raised blood pressure and strokes.

Aged↗
PubMed1996

Vitamin C status and respiratory function.

OBJECTIVE: To examine the cross sectional relationship between respiratory function and plasma vitamin C. DESIGN: Cross sectional analysis. SETTING: Population based study. SUBJECTS: 835 Men and 1025 women aged 45 to 75 registered with GP practices in Norfolk. INTERVENTIONS: Completion of health and lifestyle questionnaire and attendance for a health check. MAIN OUTCOME MEASURES: Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and non fasting plasma vitamin C. RESULTS: Plasma vitamin C was positively correlated, after adjustment for age and height, with both FEV1 (r = 0.17, P < 0.001) and FVC (r = 0.14, p < 0.001) in men. The association in women was weaker and not statistically significant. Adjusting for other possible factors and exclusion of various groups did not alter the observed associations. The differences in FEV1 and FVC in men, adjusted for age, height and cigarette smoking, for a 50 micromol/L difference in vitamin C were 0.22 litres (95% CI 0.10-0.33) and 0.23 litres (95% CI 0.09-0.37) respectively. The population distribution was shifted such that 12.1% of men with vitamin C levels < or = 30 micromol/L had an FEV1 of less than two litres, compared with 4.6% with levels > or = 60 micromol/L. CONCLUSIONS: These findings are consistent with other studies of vitamin C and respiratory function and suggest that vitamin C may be protective for lung function through the whole normal range of dietary intake and lung function.

Aged↗
PubMed1996

Vitamin C status and serum lipids.

OBJECTIVES: To examine the cross sectional relationship between plasma vitamin C and serum lipids. DESIGN: Cross-sectional analysis. SETTING: Population based study. SUBJECTS: 835 Men and 1025 women aged 45-75 registered with GP practices in Norfolk. INTERVENTIONS: Completion of health and lifestyle questionnaire and attendance for a health check. MAIN OUTCOME MEASURES: Non fasting plasma vitamin C and serum lipids. RESULTS: Plasma vitamin C was not correlated with serum total cholesterol or LDL cholesterol in men or women. In women plasma vitamin C was positively correlated with HDL cholesterol r = 0.15 (P < 0.001) and negatively correlated with triglyceride r = -0.17 P < 0.001). These correlations persisted after adjustment for age and body mass index. The association in men was weaker and after adjustment for age and body mass index was no longer statistically significant. Exclusion of subjects taking vitamin supplements and those with known hyperlipidaemic did not affect the findings. The difference in HDL cholesterol, adjusted for age, body mass index and alcohol intake, for a 50 micromol/l difference in vitamin C, estimated using linear regression, was 0.11 mmol/l in women. The difference in triglyceride, adjusted for age and body mass index was -0.16 mmol/l in women. CONCLUSIONS: Plasma vitamin C level may be a marker of other factors; nevertheless these results are consistent with other published work indicating that a high intake of vitamin C from food raises serum HDL cholesterol and lowers serum triglyceride.

Aged↗
PubMed1995

Incremental prognostic value of exercise thallium-201 myocardial single-photon emission computed tomography late after coronary artery bypass surgery.

OBJECTIVES: This study assessed the incremental prognostic value of exercise thallium-201 myocardial perfusion single-photon emission computed tomography (SPECT) performed > or = 5 years after coronary artery bypass surgery. BACKGROUND: Thallium-201 scintigraphy has shown significant prognostic value in a variety of populations with suspected and known coronary artery disease. However, its value in patients with previous bypass surgery remains unknown. METHODS: We studied 294 patients who were prospectively followed up. Cox proportional hazards models for prediction of "hard" events (cardiac death and nonfatal infarctions) were constructed, with variables considered for inclusion in hierarchic order: clinical and exercise data first, followed by scintigraphic information. RESULTS: Mean (+/- SD) follow-up duration after scintigraphy was 31 +/- 11 months. There were 20 cardiac deaths and 21 nonfatal acute myocardial infarctions. Twenty-nine patients had late (> 60 days after thallium-201 SPECT) revascularization procedures or underwent repeat bypass surgery or percutaneous transluminal angioplasty. Shortness of breath and peak exercise heart rate were the most important clinical predictors of hard events. Two scintigraphic variables added significant prognostic information to the clinical model: the thallium-201 summed reversibility score (summation of segmental differences between stress and redistribution scores) and the presence of increased lung uptake of the radiotracer. The global chi-square statistic for this model was twice as high as that for the clinical/exercise model alone (49.7 vs. 24.2). When a second multivariate Cox model was built adding "soft" events (i.e., late revascularization procedures) as outcomes of interest, the summed reversibility score was selected as an independent scintigraphic predictor of events. The global chi-square statistic for this model was 50.7, three times as high as that for the clinical/exercise model alone. CONCLUSIONS: After evaluation of treadmill and exercise data, thallium-201 myocardial perfusion SPECT provided incremental prognostic information in patients late after bypass.

Aged↗
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↗
PubMed1995

Development of a scoring system to judge the scientific quality of information from case-control and cohort studies of nutrition and disease.

A scoring system was developed to help judge the scientific quality of observational epidemiologic studies linking diet with risk of cancer. The scoring system was developed from key headings used in developing research protocols and included questions under headings: three for case-control studies (dietary assessment, recruitment of subjects, and analysis) and four for cohort studies (dietary assessment, definition of cohort, ascertainment, and analysis). Points were awarded for questions in each section, and a total score was derived. Interobserver variation was assessed for five case-controls and five cohort studies for 13 observers: 1 observer repeated the assessment of each paper. Absolute scores and ranking within observer were assessed. There was good agreement between observers in the ranking of studies. Papers that scored higher presented sufficient detail to enable the questions in the scoring system to be answered more easily. For some studies, the information required was either not collected or, if it was collected, not presented. In either case, the frequent lack of information available to judge papers raises questions about the editorial policy and review process of journals publishing dietary studies as much as it does about the scoring system. Applying the scoring system to a review of meat and cancer risk suggested that, taking the score into account, from what seemed like a large literature, there were relatively few studies that scored well (defined as a score > 65%), but these studies tended to provide more consistent information.

Case-Control Studies↗
PubMed1995

Antagonism by SB 204070 of 5-HT-evoked contractions in the dog stomach: an in-vivo model of 5-HT4 receptor function.

The ability of 5-hydroxytryptamine (5-HT) to evoke contractile activity in the gastric Heidenhain pouch was measured in conscious dogs using a method in which 5-HT4 receptor-antagonist activity can be measured in-vivo. At doses of 5-HT which evoked short-lived measurable responses (5 or 10 micrograms kg-1, i.v.), it was found that this activity was greatly reduced by atropine (100 micrograms kg-1, i.v.), but was unaffected by methysergide, methiothepin, ketanserin (each at 100 micrograms kg-1, i.v.) or granisetron (10 or 100 micrograms kg-1, i.v.). At best SDZ 205-557 2-diethylaminoethyl-[2-methoxy-4-amino-5-chloro] benzoate; 100 micrograms kg-1, i.v.) reduced the action of 5-HT in 4/5 animals and increased it in the other but its effects were variable in magnitude and not consistently maintained. However, the more potent and selective 5-HT4-receptor antagonist SB 204070 (1-butyl-4-piperidinylmethyl 8-amino-7-chloro-1, 4-benzodioxan-5-carboxylate hydrochloride) dose-dependently antagonized the 5-HT-evoked contractions in all dogs tested. This action was reversible, but long-lasting with an effective half-life of 18.0h when administered at 1 microgram kg-1. The estimated ID50 value was 0.55 microgram kg-1.

4-Aminobenzoic Acid↗
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

Gastrointestinal monitoring of DNA-damaging agents with magnetic microcapsules.

Semi-permeable, magnetically recoverable, reactive microcapsules of several types were developed for gastrointestinal (GI) monitoring of several kinds of DNA-damaging agents in relation to (i) systematic dietary variations designed to discriminate the GI effects of food components known to modulate colorectal cancer risk, and (ii) then thereby to achieve the identification of a range of endogenous agents and their dietary sources. These microcapsules contained as targets either amino functions (for alkylating agents), 14CH3 functions (to detect cross-linking agents and reactive oxygen species precursors), or a copper porphyrin (for carcinogens having planar molecular structure). Other microcapsules had a cleavable target based on guanine, which is shown to trap endogenous agents and a [14C]BaP metabolites in male F344 rats consuming a putative high-risk diet (high fat, high meat, low fibre non-starch polysaccharide (NSP)), but not significantly when consuming the contrasting low-risk diet. Detailed investigations of the action of fibre NSP and fat showed that increased intake from low to high levels of the British diet range enhanced or decreased several carcinogenesis-relevant end-points more than two-fold. Detection of these disproportionately large effects on microcapsule trapping, hepatic DNA adducts from endogenous agents, colorectal mucosal cell mitoses/micronuclei, endogenous cross-linking agents, and gut microfloral enzyme activities (a) are consistent with epidemiological data on the importance of these components and (b) provide the basis for establishing with microcapsules some potential dietary preventive measures in volunteers.

Animals↗
PubMed1993

Magnetic microcapsule exploration in the gastrointestinal cavity of the origins of colorectal cancer-associated DNA-damaging agents in the human diet.

Magnetically recoverable, semipermeable microcapsules have been devised for covalent entrapment of reactive substances in the intestinal cavity to biomonitor potentially DNA-damaging agents and the effects of etiologically important components of the human diet. These microcapsules have been shown to trap five types of agents in vivo, namely, carcinogen electrophiles, nitrosating agents, mutagens/carcinogens having a planar molecular structure, and as-yet unidentified endogenous cross-linking agents and precursors of reactive oxygen species. Substantial alterations in both total metabolites and types of metabolites trapped from [14C]benzo(a)pyrene were found to be caused by increasing (within the human intake range) the dietary levels of beef protein and dietary fiber. The system thus responds to a variety of potentially critical agents and in a manner consistent with epidemiologically important dietary modulators for colorectal carcinogenesis. Work toward recognizing entrapped endogenous agents has also begun.

Alkylating Agents↗
PubMed1992

The neuropharmacology of loperamide-induced emesis in the ferret: the role of the area postrema, vagus, opiate and 5-HT3 receptors.

Loperamide, an opiate receptor agonist, commonly used in the treatment of diarrhoea, reliably induced emesis in the ferret, when given subcutaneously. The response latency was short (less than 10 min) and the emesis lasted for approx 70 min. The dose-response curve for the emetic response was "bell-shaped" and all animals responded at 0.5 mg/kg but none at 5 mg/kg (s.c.). The response was unaffected by dopamine D2 receptor antagonism (domperidone 1.0 mg/kg, s.c.) or 5-HT3 receptor antagonism (granisetron or ondansetron 1.0 mg/kg, s.c.). The onset of the response was delayed for about 60 min by naloxone or naloxone methiodide (1.0 mg/kg, s.c.) and abolished by naloxanazine (1.0 mg/kg, s.c.), reported to be relatively selective for mu receptors. The results implicate mu receptors (possibly mu 1) in the induction of emesis by loperamide and provide some support for activation of opiate receptors also having anti-emetic effects, as suggested in previous studies. The emetic response to loperamide was unaffected by abdominal vagotomy but was abolished by ablation of the area postrema, indicating that loperamide-induced emesis may be used as a test for ablation of the area postrema in studies of the emetic mechanism in the ferret.

Animals↗
PubMed1992

Are all 5-HT3 receptor antagonists the same?

A number of 5-HT3 receptor antagonists are currently in clinical development as antiemetics. In this paper we focus on two of these antagonists, granisetron and ondansetron, and compare their antimetic activity against cisplatin (10 mg/kg i.v.)- or whole body X-irradiation (200 rads)-induced emesis in the conscious ferret. The results presented here have been discussed in the light of the recently published literature. Our data suggest that in comparison to ondansetron, granisetron is a more potent, longer acting and pharmacologically "cleaner" compound with a more conventional dose-response profile. The possible impact of these features upon the performance of these compounds in the clinic is discussed particularly with respect to dosing regimens and clinical efficacy. Differences appear to be emerging between granisetron and ondansetron in both these respects, although a direct head-to-head clinical comparison has yet to be carried out. This would involve studies monitoring a sufficiently high number of patients receiving severely emetogenic regimes to allow real clinical differences to be detected with the appropriate statistical power.

Animals↗
PubMed1992

Morphine 6-glucuronide: a metabolite of morphine with greater emetic potency than morphine in the ferret.

1. The emetic potencies of morphine and its metabolite morphine 6-glucuronide have been determined in the ferret by constructing dose-response curves for mean total retches and vomits for subcutaneous doses of 0.05 mg kg-1 to 5 mg kg-1. Morphine 6-glucuronide induced retching and vomiting at lower doses than morphine and at a maximal dose induced more retching and vomiting than morphine. 2. The emesis induced by both morphine and morphine 6-glucuronide was abolished by the preadministration of naloxone (0.5 mg kg-1 s.c.). 3. The 5-HT3 receptor antagonists granisetron and ondansetron (1 mg kg-1, s.c.) failed to abolish or reduce emesis induced by either compound. 4. At a high-dose (5 mg kg-1), morphine but not morphine 6-glucuronide failed to induce emesis and abolished the emesis induced by the cytotoxic drug, cyclophosphamide (200 mg kg-1, i.p.). 5. Preliminary pharmacokinetic studies of intravenous and subcutaneous morphine and morphine 6-glucuronide revealed that morphine 6-glucuronide accounts for less than 1% of the metabolic product of morphine in the ferret. Peak plasma levels of the two compounds after their subcutaneous administration were obtained within 10 min. The metabolic profile of morphine was not dose-dependent. There was no relationship between plasma level and emetic response for either compound.

Animals↗