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S J Lewis

Publications and source records attributed to S J Lewis.

At least 73 records · Page 4Linked to original sources
PubMed1999

Net nutrient flux in visceral tissues of lambs fed diets differing in supplemental nitrogen source.

Eight multicatheterized wethers (35.9 +/- .8 kg BW) were used in a replicated 4 x 4 Latin square design to measure N retention and net uptake and release of plasma metabolites across the portal-drained viscera (PDV), hepatic (HEP), and total splanchnic (TS) tissues in response to changes in supplemental N source. Treatments selected to provide different amounts of undegradable intake protein (UIP) were urea, soybean meal (SBM), poultry by-product meal (PBM), and bloodmeal:corn gluten meal (BMCGM; 50:50 CP basis). Diets (urea, SBM, PBM, and BMCGM) contained 12.9, 13.8, 13.6, and 13.2% CP, respectively. Periods were 10 d, with total feces and urine collected on d 7 to 10 and blood sampled on d 10. Wethers were fed at 2% of BW in 12 daily portions. Nitrogen retention was 2.2, 3.3, 4.1, and 4.4 g/d for urea, SBM, PBM, and BMCGM, respectively. Urea had less (P < .01) N retention than SBM, PBM, and BMCGM; SBM had less N retention (P < .01) than PBM and BMCGM. Arterial, portal, and hepatic plasma flows were greater (P < .09) for SBM than for PBM and BMCGM (21 vs 16, 17; 84 vs 72, 72; 105 vs 87, 88 L/h). Portal plasma flow was greater (P < .10) for urea than for SBM, PBM, and BMCGM (85 vs 84, 72, 72 L/h). Portal-drained viscera and TS alpha-amino N (AAN) fluxes were less (P < .05) for PBM than for BMCGM (20.5 vs 26.6 and 7.2 vs 15.1 mmol/h), but TS AAN flux was less (P < .05) for urea than for SBM, PBM, and BMCGM (6.9 vs 16.9, 7.2, 15.1 mmol/h). Portal-drained viscera flux and HEP removal of NH3 N were greater (P < .001) for SBM than for PBM and BMCGM (27.7 vs 19.4, 20.6; -28.1 vs -20.0, -21.4 mmol/h). Gut use was less (P = .07) and HEP and TS fluxes of urea N were greater (P < .01) for SBM than for PBM and BMCGM (-4.92 vs -8.32, -7.93; 25.87 vs 16.54, 20.00; 20.95 vs 8.22, 12.07 mmol/h). These data suggest that PBM and BMCGM improved efficiency of N use compared with urea and SBM by reducing urinary N loss.

Animal Feed↗
PubMed1999

Efficacy of azathioprine as second-line treatment in pulmonary sarcoidosis.

BACKGROUND AND AIM OF WORK: Immunosuppressives such as azathioprine are occasionally used in sarcoidosis where corticosteroids cannot be used because of poor response, contraindications or unacceptable side effects. The aim of this study was to assess the efficacy and safety of azathioprine in the treatment of pulmonary sarcoidosis. METHODS: A retrospective study was performed on patients in the Respiratory Clinic of the university teaching hospital on all biopsy-proven sarcoid treated with azathioprine between 1969 and 1993 (n = 10). All had previously shown only partial (n = 6) or no (n = 4) response to high dose oral corticosteroids. Azathioprine in a dose of 100-150 mg was administered daily, while continuing a small dose of oral corticosteroid. Patients underwent regular clinical evaluation, pulmonary function testing and chest radiography. RESULTS: In one patient the course was too brief to evaluate (26 days). Two patients had significant and sustained improvement in lung function (vital capacity increasing from 72% to 89% and from 49% to 79% of predicted respectively, and transfer factor from 78% to 114% and from 27% to 49% of predicted respectively), and chest radiograph cleared. Two patients had short-lived improvement and steroid-sparing effect. In the remainder (n = 5), no benefit was observed. No patient responded to azathioprine who had failed to respond to high dose corticosteroids. There was no significant toxicity. CONCLUSIONS: Azathioprine may provide a safe alternative to corticosteroids when a steroid-sparing effect is required, but it is unlikely to be effective in patients who fail to respond to high dose corticosteroids and/or have radiographic evidence of significant fibrosis.

Adrenal Cortex Hormones↗
PubMed1999

Family size, infections, and asthma prevalence in New Zealand children.

We conducted a prevalence case-control study to investigate the relation between family composition, infection, and development of asthma at age 7-9 years. Potential cases (399) and controls (398) were selected from the Wellington, NZ, arm of the International Study of Asthma and Allergies in Childhood, a population-based prevalence study. Further screening questions restricted cases to children with a diagnosis of asthma and current medication use (N = 233) and restricted controls to children without a history of wheezing and no diagnosis of asthma (N = 241). After controlling for confounders (including infections, atopy, and socioeconomic status), family size was strongly related to asthma. Having no siblings [prevalence odds ratio (POR) = 2.51; 95% confidence interval (CI) = 1.05-6.01] or one sibling (POR = 1.86; 95% CI = 1.14-3.03) was associated with an increased risk of asthma compared with having more than one sibling. Parent-reported rubeola infection (and possibly other similar viral exanthems) was independently associated with a decreased risk of asthma (POR = 0.48; 95% CI = 0.27-0.83), but reported pertussis infection (POR = 1.57; 95% CI = 0.58-4.24) and day care attendance in the first year of life (POR = 1.81; 95% CI = 0.93-3.51) were not strongly associated with increased risks of asthma.

Asthma↗
PubMed1998

Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) trial.

BACKGROUND: A majority of all myocardial infarctions occur in patients who are 65 years of age or older and have average cholesterol levels, but little information is available on whether cholesterol lowering in such patients reduces the rate of recurrent cardiovascular disease. OBJECTIVE: To determine whether pravastatin reduces the rate of recurrent cardiovascular events in older patients. DESIGN: Subset analysis of a randomized, controlled trial. SETTING: 80 hospitals and affiliates in the United States and Canada. PATIENTS: 1283 patients aged 65 to 75 years who had had myocardial infarction and had a plasma total cholesterol level less than 6.2 mmol/L (240 mg/dL) and a low-density lipoprotein cholesterol level of 3.0 to 4.5 mmol/L (115 to 174 mg/dL). INTERVENTION: Pravastatin, 40 mg/d, or placebo. MEASUREMENTS: Five-year event rates of major coronary events (coronary death, nonfatal myocardial infarction, angioplasty, or bypass surgery) and stroke. RESULTS: Major coronary events occurred in 28.1% of placebo recipients and 19.7% of pravastatin recipients (difference, 9.0 percentage points [95% CI, 4 to 13 percentage points]; relative risk reduction, 32%; P < 0.001). Coronary death occurred in 10.3% of the placebo group and in 5.8% of the pravastatin group (difference, 4.6 percentage points [CI, 1.9 to 6.5 percentage points]; relative risk reduction, 45%; P = 0.004). Stroke incidence was 7.3% in the placebo group and 4.5% in the pravastatin group (absolute reduction, 2.9 percentage points [CI, 0.3 to 4.5 percentage points]; relative reduction, 40%; P = 0.03). The numbers of older patients needed to treat for 5 years were 11 (CI, 8 to 24) to prevent a major coronary event and 22 (CI, 15 to 53) to prevent a coronary death. For every 1000 older patients treated, 225 cardiovascular hospitalizations would be prevented compared with 121 hospitalizations in 1000 younger patients. CONCLUSIONS: In older patients with myocardial infarction and cholesterol levels in the average range, pravastatin is associated with a clinically important reduction in risk for major coronary events and stroke. Given the high cardiovascular event rate in older patients, the potential for absolute benefit in this age group is substantial.

Aged↗
PubMed1998

Blockade of beta-adrenoceptors enhances cAMP signal transduction in vivo.

The aim of this study was to determine whether the blockade of beta-adrenoceptors would enhance cAMP-mediated signal transduction processes in vivo. The administration of the membrane permeable cAMP analogue, 8-(4-chlorophenylthiol)-cAMP (8-CPT-cAMP, 10 micromol/kg, i.v.) produced an increase in heart rate (+27 +/- 2%, P < 0.05), a fall in mean arterial blood pressure (-21 +/- 3%, P < 0.05) and falls in hindquarter (-12 +/- 3%, P < 0.05) and mesenteric (-32 +/- 3%, P < 0.05) vascular resistances in pentobarbital-anesthetized rats. The beta-adrenoceptor antagonist, propranolol (1 mg/kg, i.v.) lowered heart rate (-12 +/- 3%, P < 0.05) but did not affect mean arterial blood pressure or vascular resistances. The tachycardia, hypotension and vasodilation produced by 8-CPT-cAMP were exaggerated after administration of propranolol (P < 0.05 for all comparisons). The nitric oxide-donor, sodium nitroprusside (2 microg/kg, i.v.), produced falls in mean arterial blood pressure and vascular resistances of similar magnitude to those produced by 8-CPT-cAMP. These sodium nitroprusside-induced responses were unaffected by propranolol (P < 0.05 for all comparisons). Sodium nitroprusside also produced a minor increase in heart rate (+5 +/- 1%, P < 0.05) which was abolished by propranolol. These findings suggest that 8-CPT-cAMP directly increases heart rate and that blockade of beta-adrenoceptors enhances the potency of cAMP within the heart and vasculature.

Adrenergic beta-Antagonists↗
PubMed1998

The lack of therapeutic effect of Saccharomyces boulardii in the prevention of antibiotic-related diarrhoea in elderly patients.

Diarrhoea is a common side effect of antibiotic therapy, especially in the elderly. Saccharomyces boulardii is a non-pathogenic yeast which has been demonstrated to reduce the frequency of diarrhoea in patients due to a variety of causes. We set out to assess its role in preventing antibiotic-related diarrhoea. Consecutive patients over the age of 65 admitted to medical wards, and who were being prescribed antibiotics, were randomized to receive either S. boulardii 113 g twice daily or placebo for as long as they received antibiotics. Bowel habit was monitored using a record of interdefaecatory intervals (IDI) and stool form graded 1-4 (hard to liquid). Stool samples were tested every fourth day for Clostridium difficile toxin. Of the 72 patients randomized, 69 completed the study. There was no difference in sex, age, duration of antibiotic use, length of hospital stay, IDI, stool form, the proportion of patients receiving laxatives, the number of patients experiencing watery stools (seven vs. five), or the presence of C. difficile toxin (five vs. three). No side effects were attributable to S. boulardii. There was no evidence that the concomitant use of S. boulardii with antibiotics alters patients' bowel habits or prevents the appearance of C. difficile toxin in the stool. Thus, S. boulardii cannot be recommended as a 'natural' way to prevent antibiotic-related diarrhoea. This highlights the need for proper evaluation of probiotics before their unrestricted use in medical practice.

Aged↗
PubMed1998

Cholesterol and coronary heart disease in women.

Coronary heart disease (CHD) is the leading cause of death for women. Early studies suggested that CHD was more benign in women than in men. These early studies resulted in limited availability of studies of coronary risk prevention and lipid lowering on women. The realization that women are at high risk for CHD events, however, has led to increased data on the benefit of risk prevention and cholesterol lowering in women. Current data support recommendations for aggressive lipid lowering in women with existing CHD, or who are at risk for developing CHD.

Aged↗
PubMed1998

Effect of pravastatin on cardiovascular events in women after myocardial infarction: the cholesterol and recurrent events (CARE) trial.

OBJECTIVES: We sought to determine the effect of pravastatin on recurrent cardiovascular events in women with average cholesterol levels after myocardial infarction (MI). BACKGROUND: Little information is available on the effectiveness of lipid lowering in secondary prevention of coronary heart disease (CHD) in women; in particular, those with CHD and average cholesterol levels. METHODS: In the Cholesterol and Recurrent Events (CARE) trial, 576 postmenopausal women, between 3 and 20 months after MI, with a total cholesterol level <240 mg/dl and a low density lipoprotein cholesterol level 115 to 174 mg/dl, were randomized to receive pravastatin 40 mg/day or matching placebo for a median follow-up period of 5 years. The main outcome measures were combined coronary events (coronary death, nonfatal MI, percutaneous transluminal coronary angioplasty [PTCA] or coronary artery bypass graft surgery [CABG]), the primary trial end point (coronary death or nonfatal MI) and stroke. RESULTS: Women treated with pravastatin had a risk reduction of 43% for the primary end point (p = 0.035), 46% for combined coronary events (p = 0.001), 48% for PTCA (p = 0.025), 40% for CABG (p = 0.14) and 56% for stroke (p = 0.07). The 3,583 men in the CARE trial also showed a reduction in risk, but the magnitude tended to be less. Pravastatin improved plasma lipids similarly in men and women. There were no differences in risk of coronary events in the placebo group between men and women. Minor differences between men and women were present in baseline characteristics and treatment for MI, in general, conferring a higher risk status and a lower incidence of CABG in the women. CONCLUSIONS: Pravastatin led to significant early reduction of a wide range of cardiovascular events in post-MI women with average cholesterol levels.

Adult↗
PubMed1998

Review article: the use of biotherapeutic agents in the prevention and treatment of gastrointestinal disease.

There is presently a lack of well conducted clinical trials demonstrating any significant benefits of probiotics in humans. With the exception of diarrhoea due to rotavirus infection in children there is little evidence from randomized, double-blind, placebo-controlled studies that bacterial probiotics have a significant beneficial action in preventing diarrhoea of any cause. The yeast Saccharomyces boulardii has been shown to be of benefit in the prevention of antibiotic-associated diarrhoea but not in preventing infection with Clostridium difficile. S. boulardii may also be of benefit in preventing relapse of C. difficile infection. Because of the simplicity of in vitro systems and some animal models, beneficial characteristics of probiotics such as the ability of bacteria to bind to epithelial surfaces are not always transferable to humans. Thus any postulated benefit from consumption of probiotic bacteria should only be accepted as fact after testing in clinical studies. This review outlines our present knowledge of the mode of action of probiotics and presents the data from clinical trials on their use.

Anti-Bacterial Agents↗
PubMed1998

Intestinal absorption of oestrogen: the effect of altering transit-time.

OBJECTIVE: The mechanism by which a high fibre diet may reduce serum oestrogens is unknown. We hypothesized that time is a rate-limiting factor in oestrogen absorption from the colon so that changes in colonic transit-rate affect the proportion of oestrogen that is deconjugated and/or absorbed. AIM: To determine if alteration of intestinal transit rate would influence the absorption of an oral dose of oestradiol glucuronide. PARTICIPANTS: Twenty healthy postmenopausal women recruited by advertisement. SETTING: Department of Medicine, Bristol Royal Infirmary. METHODS: Volunteers consumed, in turn, wheat bran, senna, loperamide and bran shaped plastic flakes, each for 10 days with a minimum 2 week washout period between study periods, dietary intake being unchanged. Before and in the last 4 days of each intervention whole-gut transit-time, defecation frequency, stool form, stool beta-glucuronidase activity, stool pH and the absorption of a 1.5 mg dose of oestradiol glucuronide were measured. RESULTS: Wheat bran, senna and plastic flakes led to the intended reduction in whole-gut transit-time, increase in defecatory frequency and increase in stool form score. Loperamide caused the opposite effect. The length of time the absorbed oestrogen was detectable in the serum fell with wheat bran and senna, although this was only significant for oestradiol. Oestrone, but not oestradiol, was detectable for a longer time with loperamide. Plastic flakes had no effect on either oestrogen. Areas under the curve did not change significantly but tended to fall with the three transit-accelerating agents and to rise with loperamide. CONCLUSION: Our data indicate there is likely to be an effect of intestinal transit on the absorption of oestrogens but more refined techniques are needed to characterize this properly.

Dietary Fiber↗
PubMed1998

Peroxynitrite-mediated vasorelaxation: evidence against the formation of circulating S-nitrosothiols.

Peroxynitrite-induced relaxation of isolated vessels may involve the formation of S-nitrosothiols. This study characterized the hemodynamic effects of systemically injected peroxynitrite in penotobarbital sodium-anesthetized rats and determined whether these effects were due to the formation of S-nitrosothiols. We utilized L-penicillamine, which attenuates the hemodynamic effects of systemically injected S-nitrosothiols. The hemodynamic effects of peroxynitrite and the S-nitrosothiols L-S-nitrosocysteine, L-S-nitrosoglutathione, and S-nitrosoalbumin were determined before and 25 min after the administration of L-penicillamine or saline. Peroxynitrite and the S-nitrosothiols produced dose-dependent reductions in mean arterial pressure and mesenteric and hindquarter vascular resistances. The hypotensive and vasodilator effects of the S-nitrosothiols were significantly reduced by L-penicillamine. In contrast, the hemodynamic actions of peroxynitrite were unaffected by L-penicillamine. Therefore, peroxynitrite produces hypotensive and vasodilator responses in anesthetized rats that are unlikely to be due to the formation of circulating S-nitrosothiols. The mechanisms by which peroxynitrite produces vasodilatation in vivo remain to be determined.

Animals↗
PubMed1998

Hemodynamic effects of L-glutamate in NTS of conscious rats: a possible role of vascular nitrosyl factors.

This study examined peripheral mechanisms responsible for changes in mean arterial blood pressure, heart rate, and renal, mesenteric, and hindquarter vascular resistances produced by microinjections of L-glutamate (L-Glu) into the nucleus tractus solitarii (NTS) of conscious rats. Microinjection of L-Glu produced an initial pressor response, bradycardia, and vasoconstriction in each vascular bed. Subsequent hindquarter vasodilation was observed. After prazosin was administered, L-Glu produced initial hypotension that was probably due to reduced cardiac output. This hypotension was followed by hindquarter vasodilation. Inhibition of nitric oxide synthesis did not affect the initial hypotension or bradycardia in rats treated with prazosin, but the first microinjection of L-Glu after administration of prazosin and NG-nitro-L-arginine methyl ester (L-NAME) produced significantly greater hindquarter vasodilation than after administration of prazosin alone. Second and third microinjections of L-Glu produced significantly smaller hindquarter vasodilation. We conclude that 1) hemodynamic effects produced by microinjection of L-Glu into the NTS of conscious rats involves activation of the sympathetic nervous system and 2) release of preformed nitrosyl factors may mediate vasodilation in the hindquarter vascular bed.

Animals↗
PubMed1998

Attenuation of vascular relaxation after development of tachyphylaxis to peroxynitrite in vivo.

Peroxynitrite, formed endogenously by the near diffusion-limited reaction of nitric oxide with superoxide anion, induces vascular relaxation. This effect is subject to rapid tachyphylaxis, suggesting that peroxynitrite may alter subsequent vasorelaxant responses. The present study examined the effects of peroxynitrite on mean arterial pressure and hindquarter, renal, and mesenteric vascular resistances in pentobarbital-anesthetized rats. Peroxynitrite induced dose-dependent decreases in mean arterial pressure and hindquarter and mesenteric vascular resistances. The repetitive administration of peroxynitrite resulted in the rapid development of tachyphylaxis, with subsequent doses producing progressively smaller effects. After the development of tachyphylaxis to peroxynitrite, the hemodynamic effects produced by the systemic administration of acetylcholine and prostacyclin were significantly attenuated, whereas the hemodynamic responses to bradykinin and the nitric oxide donor (Z)-1-¿N-methyl-N-[6(N-methylammoniohexyl)amino]¿diazen-1-++ +ium-1, 2-diolate (MAHMA NONOate) remained unchanged. These results demonstrate that 1) peroxynitrite is a potent vasorelaxant in vivo, 2) peroxynitrite-mediated vasodilatation is subject to the development of rapid tachyphylaxis, and 3) peroxynitrite alters the vascular smooth muscle response to prostacyclin, perhaps via inactivation of vascular smooth muscle ATP-sensitive potassium channel function.

Acetylcholine↗
PubMed1998

Effect of heating on the hemodynamic responses to vasoactive agents.

During hyperthermia, vasoconstrictor tone in the viscera is lost despite high levels of sympathetic neural outflow and plasma catecholamines, suggesting that vascular responsiveness to adrenergic receptor stimulation is reduced. The purpose of this study was to determine whether adrenoceptor-mediated control of vascular resistance is altered at high body core temperatures. The hemodynamic responses to adrenoceptor agonists were examined in chloralose-anesthetized rats heated to colonic temperatures (Tco) of 37, 39, and 41.5 degrees C. Elevating Tco to 39 degrees C did not alter the hemodynamic responses to any of these agents. Further heating to 41.5 degrees C markedly attenuated the hemodynamic responses to alpha- and beta-adrenoceptor agonists. Similarly, the regional and systemic hemodynamic responses to ANG II and endothelin were also reduced at 41.5 degrees C. In contrast, the hemodynamic responses to endothelium-dependent and -independent vasodilator agents were unchanged or slightly reduced at 41.5 degrees C. The blunted hemodynamic responses observed at 41.5 degrees C indicate that vascular reactivity to vasoconstrictor agents is reduced with hyperthermia and suggest that this nonspecific change in vascular responsiveness may contribute the circulatory collapse associated with high body temperatures.

Acetylcholine↗
PubMed1998

Effect of heating on vascular reactivity in rat mesenteric arteries.

Vasoconstriction in the viscera is one of the primary cardiovascular adjustments to heating. Local temperature can influence vascular responsiveness to catecholamines and sympathetic nerve activity. Therefore, we hypothesized that heating would alter vascular reactivity in rat mesenteric arteries. Concentration-response curves to norepinephrine, phenylephrine, potassium chloride (KCl), calcium, acetylcholine, and sodium nitroprusside were obtained in vascular ring segments from rat mesenteric arteries at 37 and 41 degrees C. In some rings, basal tension increased slightly during heating. Heating to 41 degrees C did not alter the contractile responses to norepinephrine in endothelium-intact or -denuded rings but augmented the responses to KCl and calcium in endothelium-intact rings. The potentiating effect of heating on the responses to KCl and calcium was eliminated after endothelium removal. In contrast, the relaxant responses to acetylcholine and sodium nitroprusside were significantly attenuated at 41 degrees C. Collectively, these results demonstrate that heating alters vascular reactivity in rat mesenteric arteries. Furthermore, these data imply that heating reduces the ability of vascular smooth muscle to relax, possibly due to a decrease in sensitivity to nitric oxide.

Adrenergic Agonists↗
PubMed1997

Heterologous desensitization of beta-adrenoceptor signal transduction in vivo.

The hemodynamic actions of pituitary adenylate cyclase-activating polypeptide (PACAP-27) rapidly diminish upon repeated i.v. injection in rats treated with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). We now report that the beta-adrenoceptor agonist isoproterenol (0.5 microg/kg, i.v.) produces pronounced hypotensive and vasodilator effects in anesthetized rats pretreated with L-NAME (100 micromol/kg, i.v.). However, the hypotensive and vasodilator actions of isoproterenol were markedly diminished in L-NAME-treated rats in which tachyphylaxis to PACAP was induced immediately prior to the injection of the beta-adrenoceptor agonist. This suggests that a reduction in tissue concentrations of nitric oxide-containing factors allows tachyphylaxis to PACAP-27-mediated vasodilation to occur in vivo and that this process leads to the heterologous desensitization of beta-adrenoceptor-mediated responses.

Adrenergic beta-Agonists↗