Resistant rheumatoid arthritis clinics- a necessary development?
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Antirheumatic Agents↗
Biomedical subjects
S Bingham
Publications and source records attributed to S Bingham.
Vitamin C and hyperglycemia in the European Prospective Investigation into Cancer--Norfolk (EPIC-Norfolk) study: a population-based study.
OBJECTIVE: To examine the cross-sectional association between plasma vitamin C, self-reported diabetes, and HbA1c. RESEARCH DESIGN AND METHODS: Data from a population-based study of diet, cancer, and chronic disease were analyzed. A total of 2,898 men and 3,560 women 45-74 years of age who were registered with general practices in Norfolk, U.K., were recruited to the European Prospective Investigation Into Cancer-Norfolk study between 1995 and 1998. RESULTS: Mean plasma vitamin C levels were significantly higher in individuals with HbA1c levels < 7% than in those with self-reported diabetes or prevalent undiagnosed hyperglycemia (HbA1c > or = 7%). An inverse gradient of mean plasma vitamin C was found in both sexes across quintiles of HbA1c distribution < 7%. The odds ratio (95% CI) of having prevalent undiagnosed hyperglycemia per 20 micromol/l (or 1 SD) increase in plasma vitamin C was 0.70 (0.52-0.95) (adjusted for sex, age, BMI, waist-to-hip ratio, tertiary education, any use of dietary supplements, vegetarian diet, alcohol consumption, physical activity, dietary vitamin E, dietary fiber, dietary saturated fat, and smoking history). The unadjusted change in HbA1c per 20 micromol/l increase in vitamin C estimated by linear regression was -0.12% (-0.14 to -0.09) in men and -0.09% (-0.11 to -0.07) in women. After adjusting for the possible confounders, these values were -0.08% (-0.11 to -0.04) in men and -0.05% (-0.07 to -0.03) in women. CONCLUSIONS: An inverse association was found between plasma vitamin C and HbA1c. Dietary measures to increase plasma vitamin C may be an important public health strategy for reducing the prevalence of diabetes.
Aged↗
The search for novel migraine therapies: experimental models.
The identification and development of the potent 5-HT1B/1D agonist, sumatriptan has resulted in new therapeutic opportunities for the treatment of migraine and a number of chemically novel agents with a similar mechanism of action have been identified. Whilst these agents are optimised to enhance the therapeutic effect of sumatriptan, development of mechanistically novel therapies may provide new directions for the care of migraine sufferers. To develop new treatment paradigms, novel chemical entities should be evaluated in animal models which are predictive of therapeutic efficacy e.g.: in animal models where sumatriptan has shown activity, or the pathophysiological processes involved in the disease must be targeted. Therefore, investigation of mechanisms underlying cortical activity and its involvement in the activation of trigeminal vascular pathways may allow better understanding of the disease and result in the identification of new non-triptan-like therapies.
Animals↗
Protein degradation in the large intestine: relevance to colorectal cancer.
Colorectal cancer is the second most common form of cancer death in Western countries. Diet has been implicated in the aetiology of this disease. Epidemiological evidence suggests that diets high in meat and fat and low in fermentable carbohydrate increase colorectal cancer risk. One mechanism that could explain the association with meat is increased colonic protein metabolism due to increased protein intake from high meat diets. Products of colonic protein degradation and metabolism include ammonia, phenols, indoles and amines which have been shown to exert toxic effects in vitro and in animal models. These compounds are present in faecal samples suggesting that they may exert gut mucosal effects. Human studies have shown that colonic protein metabolism via the gut microflora is responsive to dietary protein as faecal ammonia and urinary phenolic compound concentrations increase in response to increased intake of protein rich foods. Other toxic metabolites from dietary protein precursors such as N-nitroso compounds and sulphides are also formed. Recent work has shown that diets high in meat, fat and low in fibre increase human faecal water genotoxicity. It is likely that metabolites from colonic protein metabolism contribute to this increase in genotoxicity during high meat intakes.
Adult↗
Sewing-pin perforation of the appendix into the bladder.
We report a 2.5-year-old child who presented with an acute abdomen caused by the perforation of a sewing pin through her appendix that had started to penetrate the wall of the bladder.
Abdomen, Acute↗
Plasma vitamin C: what does it measure?
OBJECTIVE: To examine the association between self-reported consumption of foods and plasma vitamin C levels. DESIGN: A cross-sectional analysis of dietary data and plasma vitamin C levels. Subjects placed the following foods into frequency categories: fresh fruit, leafy greens, other vegetables, fatty fish, other fish, chicken, meat, meat products, eggs, cheese and brown bread. The six frequency categories ranged from 'never' to 'at least daily'. Plasma vitamin C was measured by fluorometric assay. SETTING: A population-based cohort study in Norfolk, UK. SUBJECTS: 598 men and 566 women aged 45-74 years not taking vitamin supplements. RESULTS: Plasma vitamin C was positively correlated with intake of fresh fruit (r=0.29 in men and r=0.25 in women, P<0.001), leafy greens (r=0.20 in men P<0.001, r=0.13 in women P<0.01), other vegetables (r=0.20 in men P<0.001, r=0.14 in women P<0.01) and brown bread (r=0.28 in men, r=0.17 in women, P<0.001) and negatively associated with intake of meat products (r=-0.13 in men P=0.02, r=-0.10 in women P<0.01). The difference in plasma vitamin C between never and daily eaters of brown bread was 13.6 micronol l(-1) in men and 9.9 micromol l(-1) in women, P<0.001. CONCLUSIONS: These data suggest that plasma vitamin C is not only a marker of foods rich in vitamin C but of certain patterns of food consumption. Such patterns are likely to be population specific and might explain inconsistencies in biomarker-disease associations.
Aged↗
A method to compensate for incomplete 24-hour urine collections in nutritional epidemiology studies.
OBJECTIVE: To develop a method to make use of incomplete 24-hour urinary samples in nutritional epidemiology, especially when validating the dietary intake of nitrogen (protein), sodium and potassium. DESIGN: Urinary data for men and women collected in three different studies were evaluated. The concentration of para-aminobenzoic acid (PABA) in one 24-hour urine sample per person was compared with the concentrations of nitrogen, sodium, potassium and creatinine. SETTING: Men and women living in Cambridge, UK and women living in the town of Varberg, Sweden. SUBJECTS: In total, this study consists of data from 73 Swedish women (20-50 years of age), 165 UK women (50-65 years) and 75 UK men (55-88 years). RESULTS: On average four out of 10 people in this study had a PABA recovery below 85%. The linear regression equations for urinary excretion of nitrogen, sodium and potassium in relation to PABA recovery were y=2.3 + 0.088 x chi (r=0.99), y=45 + 0.82 x chi (r= 0.87) and y = 19 + 0.60 x chi (r= 0.93), respectively. CONCLUSIONS: The linear regression equations can be used for adjusting urinary nitrogen, sodium and potassium in urinary collections in cases where the PABA recovery is below 85%. Since it is common to obtain 24-hour urine collections with a PABA recovery below 85%, this method should increase the usefulness of biological markers of food intake in nutritional epidemiological studies and also increase the possibilities to study people that previously have been part of the drop-out group or the group with low motivation and cooperation. It is important to stress that we have not studied the relationship between PABA recovery and various urinary variables below the PABA recovery of 50%. Thus, in a case of PABA recovery below 50%, we do not recommend the use of this method to compensate for incomplete collections.
4-Aminobenzoic Acid↗
Trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the anaesthetized cat: role of endothelin(B) receptors in carotid vasodilatation.
1. The effects of intravenous administration of endothelin (ET) receptor antagonists SB-209670 (0.001-10.0 mg kg(-1)), SB-217242, SB-234551 (0.01-10.0 mg kg(-1)) and BQ-788 (0.001-1.0 mg kg(-1)) were investigated on trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the carotid vasculature of the anaesthetized cat. Comparisons were made with sumatriptan (0.003-3.0 mg kg(-1)) and alpha-CGRP8-37 (0.001-0.1 mg kg(-1)). 2. Trigeminal nerve ganglion stimulation produced frequency related increases in carotid blood flow, reductions in carotid vascular resistance and non-frequency related increases in blood pressure. Guanethidine (3 mg kg(-1), i.v.) blocked trigeminal nerve ganglion-induced increases in blood pressure but had no effect on changes in carotid flow or resistance. Maximal reductions in carotid vascular resistance was observed at 10 Hz, and this frequency was selected to investigate the effects of drugs on trigeminal nerve ganglion stimulation-induced responses in guanethidine treated cats. 3. Saline, alpha-CGRP8-37 SB-209670 and BQ-788 had little or no effect on resting haemodynamic parameters. SB-217242 (10 mg kg(-1), n=3) produced a 56% reduction in arterial blood pressure whereas SB-233451 (10 mg kg(-1), n=3) produced a 30% reduction in carotid vascular resistance. Sumatriptan produced dose-related reductions in resting carotid flow and increases (max. 104% at 0.3 mg kg(-1), n = 5) in vascular resistance. 4. SB-209670 (n=6-7), SB-217242 (n=3) and BQ-788 (n=3) produced inhibition of trigeminal nerve ganglion stimulation-induced reductions in carotid vascular resistance. Saline, SB-234551, alpha-CGRP8-37 and sumatriptan had no effect. 5. These data demonstrate ET(B) receptor blockade attenuates the vasodilator effects of trigeminal nerve ganglion stimulation in the carotid vascular bed of guanethidine pretreated anaesthetized cats.
Anesthesia↗
WHO consensus statement on the role of nutrition in colorectal cancer.
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Alcohol Drinking↗
The effects of season and alcohol intake on mineral metabolism in men.
We have examined the relationship between self-reported alcohol intake (SRAI), season and mineral metabolism in a series of 96 men aged 32 to 78 years of age. Alcohol intake was reported as between 0 and 50 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin, alkaline phosphatase, and AST initially and at 6 months. In addition, SRAI correlated with serum calcium, testosterone, estradiol, and immunoreactive parathyroid hormone (iPTH) as well as urinary calcium [per 100 mg of creatinine (Cr)], and pyridinoline crosslinks (DPC) (per 100 mg of Cr). We have divided the participants into two groups on the basis of their reported alcohol intake. Individuals with none-to-moderate intake had <8.4 oz/week of ethanol. Those with moderate or heavier intake had 8.4 oz or more of ethanol/week. Individuals with none-to-moderate SRAI had a significant seasonal increase in iPTH, osteocalcin, urine DPC/100 mg of Cr and a decrease in distal forearm bone mineral density, 25 hydroxyvitamin D (250HD), and urinary calcium/100 mg of Cr. Individuals with moderate or heavier SRAI only had significant seasonal decrease in 250HD. We have concluded that alcohol intake decreases seasonal change in serum iPTH. The biological effects of such alterations in parathyroid hormone levels include decreased seasonal loss of bone mineral density.
Adult↗
EPIC-Norfolk: study design and characteristics of the cohort. European Prospective Investigation of Cancer.
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Aged↗
Review of uptake of interventions to reduce mother to child transmission of HIV by women aware of their HIV status.
OBJECTIVES: To examine the change in uptake of interventions to reduce transmission of HIV from mothers to infants from January 1994 to July 1997. DESIGN: Review of mother-infant pairs who presented for infant diagnosis of HIV infection. SETTING: Central London hospital with facilities for diagnosis of infant HIV infection. SUBJECTS: 57 consecutive mother-infant pairs, mainly from central London but also referred from surrounding hospitals. INTERVENTIONS: Data were collected on mother's country of origin; CD4 count at delivery; plasma HIV RNA copies/ml; mode of delivery; antiretroviral therapy; infant feeding; and HIV infection in infants. MAIN OUTCOME MEASURES: HIV infection of infants. RESULTS: The vertical transmission rate was 12% (7 pairs; 95% confidence interval 3% to 22%). All mothers chose not to breast feed. The caesarean section rate was 53% (30/57). Antiretroviral therapy was taken by 68.5% (39/57) of mother-infant pairs. With antiretroviral therapy or caesarean section, or both, transmission occurred in 6% (0% to 13%) of pairs (3/50). During the 24 months of 1994 and 1995, 21% (4/19) of infants were infected with HIV; 7.9% (3/38) were infected over the 19 months January 1996 to July 1997. The caesarean section rate did not change over these periods. Use of antiretroviral therapy increased from 31.5% (6/19) to 86.8% (33/38) (P < 0.0001). CONCLUSION: Women with a diagnosis of HIV infection acted to reduce the risk of transmission to their infants. Uptake of antiretroviral therapy increased significantly over time, and the caesarean section rate was persistently high.
Africa↗
Antihypertensive efficacy of treatment regimens used in Veterans Administration hypertension clinics. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.
There is continuing uncertainty about whether morbidity and mortality of treated hypertensive patients depends on the drug(s) used to treat or only on the level of blood pressure achieved. This study was undertaken in a sample of special Veterans Administration hypertension clinics to determine which antihypertensive drugs were selected by the involved healthcare providers and how effective they were in achieving normotension. Hypertensive veterans (n = 6100) were followed in six VA Hypertension Screening and Treatment Program clinics for 46 months beginning in May 1989. Their average age was 60.7 years; 53% lived in the Stroke Belt; 46% had target organ damage, 36% were black, 23% smoked, and 10% had diabetes mellitus. Antihypertensive regimens were divided into 12 all-inclusive categories. Blood pressures were averaged at the last study visit for all patients on a regimen. The regimens of diuretic or diuretic plus beta-blocker gave the lowest average pressures (140.6/82.3 mm Hg) and calcium antagonist the highest (149.0/86.5 mm Hg). ANOVA indicated that differences between seven common regimens and also between the four single drug regimens were highly significant (P<.0001). This pattern of low treated pressure with the "old" agents and higher treated pressure with newer agents was reflected in the percentage of patients controlled below 140/90 mm Hg and the percentage uncontrolled above 159/94 mm Hg. Blacks and patients with target organ damage resembled the entire cohort in average treated diastolic blood pressure, but the former had lower and the latter had higher treated systolic blood pressure than the entire cohort.
Analysis of Variance↗
Effect of recent alcohol intake on parathyroid hormone and mineral metabolism in men.
The mechanisms by which alcohol intake, particularly moderate alcohol intake, effects bone metabolism are poorly defined. We have examined the relationship between mineral metabolism and recent self-reported alcohol intake (SRAI) across a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAI were obtained from each subject. SRAI was reported as between 0 and 45 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin (r = 0.30, p = 0.002), alkaline phosphatase (r = 0.30, p = 0.004), and aspartate aminotransferase (SGOT) (r = 0.29, p = 0.006). SRAI correlated with serum calcium corrected for albumin (r = -0.39, p < 0.001), estradiol (r = 0.43, p < 0.001), and immunoreactive parathyroid hormone (iPTH) (r = -0.51, p < 0.001), as well as urinary calcium (per 100 mg of creatinine) (r = 0.55, p < 0.001). We have arbitrarily divided the participants into two groups on the basis of their reported alcohol intake. Individuals in the first group had intakes ranging from none to moderate intake (drank 8.4 oz or less of ethanol per week, equivalent to an average of two drinks daily or less). Those in the second group had moderate or heavier intake, with >8.4 oz of ethanol intake/week. Mean serum iPTH was significantly greater in those in the first group (none to moderate), compared with the second group (moderate or heavier) (56.0 +/- 3.4 and 39.9 +/- 2.0 pM/liter, respectively). Calcium corrected for serum albumin was significantly greater in individuals in the first, compared with the second, group (9.23 +/- 0.05 vs. 8.88 +/- 0.07 mg/dl, respectively). In addition, urinary calcium (corrected per 100 mg of creatinine) was significantly lower in the former, compared with the latter (3.1 +/- 0.4 vs. 8.4 +/- 1.1 mg/100 mg of creatinine, respectively). Similarly, urinary excretion of collagen crosslinks (corrected per 100 mg of creatinine) was significantly less in men in the second group, compared with the first group (316 +/- 38 vs. 530 +/- 78 nM/100 mg of creatinine, respectively). Not surprisingly, a series of correlations between iPTH and age, 250-hydroxyvitamin D, and testosterone were significant in individuals with none to moderate SRAI, but not moderate or heavier SRAI. Significant independent predictors of serum iPTH in the entire group of men were age (beta = 0.215, p = 0.025), SRAI (beta = -0.281, p = 0.003), 250-hydroxyvitamin D (beta = -0.309, p = 0.002), and testosterone (beta = -184, p = 0.048). We have concluded that, in free-living men, alcohol intake >8.4 oz/week was associated with decreased serum iPTH concentrations.
Adult↗
Age related dietary exposure to meat products from British dietary surveys of teenagers and adults in the 1980s and 1990s.
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Adolescent↗
Meat, starch and non-starch polysaccharides, are epidemiological and experimental findings consistent with acquired genetic alterations in sporadic colorectal cancer?
International comparisons show strong inverse protective associations with starch, NSP (fibre, non-starch polysaccharides) and vegetable intakes, and positive associations with meat consumption in large bowel cancer. Estimates of relative risk from cohort investigations are in the same direction although generally weak, and red and processed meat, rather than white meat seem to be associated with elevated risk. A protective effect of starch and NSP probably arises from their marked effect on bacterial metabolism in the large bowel, which can be postulated to affect gene expression and DNA repair via increased butyrate production. Stool weight is also increased and pH reduced leading to alterations in secondary bile acid production, and mucosal cell proliferation. In rodent models, 'insoluble' sources of NSP are generally protective, although butyrate, resistant starch and soluble NSP may not reduce tumorigenesis. High levels of meat increase faecal ammonia and N-nitrosocompound (NOC) concentration. Some of the chromosomal mutations found in human colorectal cancer are consistent with effects of NOC and heterocyclic amines. More data are required from human experimental studies linking alterations in diet with known stages in carcinogenesis in the large bowel, and from large cohort studies which have collected biological samples in order that interaction between diet, biomarkers of diet, and different genotypes that may determine risk can be examined.
Animals↗
Specific mutation near the primary donor in photosystem I from Chlamydomonas reinhardtii alters the trapping time and spectroscopic properties of P700.
Time-resolved absorption and fluorescence spectroscopy were used to investigate the energy and electron transfer processes in the detergent-isolated photosystem I core particles from the site-directed mutant of Chlamydomonas reinhardtii with the histidine-656 of PsaB replaced by asparagine [HN(B656) mutation]. The specific mutation near the primary donor molecule results in a 40 mV increase in the P700/P700+ midpoint potential [Webber, A. N., Su Hui, Bingham, S. E., Kass, H., Krabben, L., Kuhn, M., Jordan, R., Schlodder, E., & Lubitz, W. (1996) Biochemistry 35, 12857-12863]. There is no indication that the HN(B656) mutation affects the spectral distribution of the antenna pigments. However, the lifetime of the trapping process measured independently by transient absorption and fluorescence spectroscopy in the mutant PSI core antenna is increased by a factor of approximately 2 (approximately 65 ps compared to approximately 30 ps in the wild-type PSI). This implies that the trapping process in the PSI antenna is limited by the process where the primary donor molecule directly participates. The HN(B656) mutation results in the appearance of a new bleaching band at 670 nm in the spectrum which is due to formation of P700+ upon photooxidation. The difference spectrum of the photoreduction of the possible primary acceptor, A0 in the mutant PSI is very similar to wild type, indicating that it is unaffected by the HN(B656) mutation. Possible mechanisms for slowing of the trapping process and the appearance of a new band in the P700 - P700+ difference spectrum of the HN(B656) PSI are discussed.
Animals↗
Selective and functional 5-hydroxytryptamine4 receptor antagonism by SB 207266.
1. The pharmacology of a novel 5-HT4 receptor antagonist, SB 207266 has been evaluated in vitro in the guinea-pig distal colon longitudinal muscle myenteric plexus (LMMP) and in vivo in the dog Heidenhain pouch. 2. SB 207266 is a highly potent antagonist of 5-HT-evoked, cholinergically-mediated contractions in the guinea-pig distal colon. Low concentrations (0.1-10 nM) produced a parallel shift to the right of the concentration-effect curve (apparent pA2 10.6 +/- 0.1) with no significant effect on the maximum response. With higher concentrations of SB 207266 (30 nM and above) the maximum response to 5-HT was reduced. 3. The antagonism seen with SB 207266 cannot be attributed to a non-selective effect since high concentrations (1 microM) had no effect on cholinergically-mediated contractions evoked by the nicotinic receptor agonist DMPP in the same preparation. 4. SB 207266 is not an irreversible antagonist since the effects of the compound were reversible upon washing of the tissue. 5. In the dog Heidenhain pouch, oral (0.1-100 micrograms kg-1) and intravenous (0.1-100 micrograms kg-1) administration of SB 207266 produced a dose-dependent antagonism of the contractions evoked by a bolus intravenous injection of 5-HT. An ID50 for SB 207266 of 1.3 micrograms kg-1 was obtained following i.v. administration and 9.6 micrograms kg-1 following oral administration. 6. The antagonistic effects of SB 207266 (0.1-100 micrograms kg-1) in the dog Heidenhain pouch were long lasting since, following oral administration, the response to 5-HT was reduced for at least 135 min. 7. SB 207266 is a highly potent, highly selective and orally active 5-HT4 receptor antagonist. This compound is the first orally active amide to be identified in this class of antagonists and as such is an important new tool in the evaluation of 5-HT4 receptor function both in vitro and in vivo.
Animals↗