The VITATOPS (vitamins to prevent stroke) Trial: Rationale and design of an international, large, simple, randomised trial of homocysteine-lowering multivitamin therapy in patients with recent transient ischaemic attack or stroke

Background: Epidemiological studies suggest that raised plasma concentrations of total homocysteine (tHcy) may be a common, causal and treatable risk factor for atherothromboembolic ischaemic stroke. Although tHcy can be lowered effectively with small doses of folic acid, vitamin B-12 and vitamin B-6, it is not known whether lowering tHcy, by means of multivitamin therapy, can prevent stroke and other major atherothromboembolic vascular events. Purpose: To determine whether vitamin supplements (folic acid 2 mg, B-6 25 Mg, B-12 500 mug) reduce the risk of stroke, and other serious vascular events, in patients with recent stroke or transient ischaemic attacks of the brain or eye (TIA). Methods: An international, multi-centre, randomised, double-blind, placebo-controlled clinical trial. Results: As of November 2001, more than 1,400 patients have been randomised from 10 countries in four continents. Conclusion: VITATOPS aims to recruit and follow up 8,000 patients between 2000 and 2004, and provide a reliable estimate of the safety and effectiveness of dietary supplementation with folic acid, vitamin B-12, and vitamin B-6 in reducing recurrent serious vascular events among a wide range of patients with TIA and stroke. Copyright (C) 2002 S. Karger AG, Basel.

Efficacy of B vitamins in lowering homocysteine in older men - Maximal effects for those with B-12 deficiency and hyperhomocysteinemia

Background and Purpose - A higher plasma concentration of total homocysteine (tHcy) is associated with a greater risk of cardiovascular events. Previous studies, largely in younger individuals, have shown that B vitamins lowered tHcy by substantial amounts and that this effect is greater in people with higher tHcy and lower folate levels. Methods - We undertook a 2-year, double-blind, placebo-controlled, randomized trial in 299 men aged >= 75 years, comparing treatment with a daily tablet containing 2 mg of folate, 25 mg of B-6, and 400 mu g of B-12 or placebo. The study groups were balanced regarding age (mean +/- SD, 78.9 +/- 2.8 years), B vitamins, and tHcy at baseline. Results - Among the 13% with B12 deficiency, the difference in mean changes in treatment and control groups for tHcy was 6.74 mu mol/L (95% CI, 3.94 to 9.55 mu mol/L) compared with 2.88 mu mol/L (95% CI, 0.07 to 5.69 mu mol/L) for all others. Among the 20% with hyperhomocysteinaemia, the difference between mean changes in treatment and control groups for men with high plasma tHcy compared with the rest of the group was 2.8 mu mol/L (95% CI, 0.6 to 4.9 mu mol/L). Baseline vitamin B12, serum folate, and tHcy were significantly associated with changes in plasma tHcy at follow-up (r = 0.252, r = 0.522, and r = -0.903, respectively; P = 0.003, <0.001, and <0.001, respectively) in the vitamin group. Conclusions - The tHcy-lowering effect of B vitamins was maximal in those who had low B12 or high tHcy levels. Community-dwelling older men, who are likely to be deficient in B12 or have hyperhomocysteinemia, may be most likely to benefit from treatment with B vitamins.

Optimising fed-batch production of recombinant proteins using the baculovirus expression vector system

Fed-batch culture can offer significant improvement in recombinant protein production compared to batch culture in the baculovirus expression vector system (BEVS), as shown by Nguyen et al. (1993) and Bedard et al. (1994) among others. However, a thorough analysis of fed-batch culture to determine its limits in improving recombinant protein production over batch culture has yet to be performed. In this work, this issue is addressed by the optimisation of single-addition fed-batch culture. This type of fed-batch culture involves the manual addition of a multi-component nutrient feed to batch culture before infection with the baculovirus. The nutrient feed consists of yeastolate ultrafiltrate, lipids, amino acids, vitamins, trace elements, and glucose, which were added to batch cultures of Spodoptera frugiperda (Sf9) cells before infection with a recombinant Autographa californica nuclear polyhedrosis virus (Ac-NPV) expressing beta-galactosidase (beta-Gal). The fed-batch production of beta-Gal was optimised using response surface methods (RSM). The optimisation was performed in two stages, starting with a screening procedure to determine the most important variables and ending with a central-composite experiment to obtain a response surface model of volumetric beta-Gal production. The predicted optimum volumetric yield of beta-Gal in fed-batch culture was 2.4-fold that of the best yields in batch culture. This result was confirmed by a statistical analysis of the best fed-batch and batch data (with average beta-Gal yields of 1.2 and 0.5 g/L, respectively) obtained from this laboratory. The response surface model generated can be used to design a more economical fed-batch operation, in which nutrient feed volumes are minimised while maintaining acceptable improvements in beta-Gal yield. (C) 1998 John Wiley & Sons, Inc.

Practical and economic advantages of choice feeding systems for laying poultry

Poultry can be managed under different feeding systems, depending on the husbandry skills and the feed available. These systems include the following: (1) a complete dry feed offered as a mash ad libitum; (2) the same feed offered as pellets or crumbles ad libitum; (3) a complete feed with added whole grain; (4) a complete wet feed given once or twice a day; (5) a complete feed offered on a restricted basis; (6) choice feeding. Of all these, an interesting alternative to offering complete diets is choice feeding which can be applied on both a small or large commercial scale. Under choice feeding or free-choice feeding birds are usually offered a choice between three types of feedstuffs: (a) an energy source (e.g. maize, rice bran, sorghum or wheat); (b) a protein source (e.g. soyabean meal, meat meal, fish meal or coconut meal) plus vitamins and minerals and (c), in the case of laying hens, calcium in granular form (i.e. oyster-shell grit). This system differs from the modern commercial practice of offering a complete diet comprising energy and protein sources, ground and mixed together. Under the complete diet system, birds are mainly only able to exercise their appetite for energy. When the environmental temperature varies, the birds either over- or under-consume protein and calcium. The basic principle behind practising choice feeding with laying hens is that individual hens are able to select from the various feed ingredients on offer and compose their own diet, according to their actual needs and production capacity. A choice-feeding system is of particular importance to small poultry producers in developing countries, such as Indonesia, because it can substantially reduce the cost of feed. The system is flexible and can be constructed in such a way that the various needs of a flock of different breeds, including village chickens, under different climates can be met. The system also offers a more effective way to use home-produced grain, such as maize, and by-products, such as rice bran, in developing countries. Because oyster-shell grit is readily available in developing countries at lower cost than limestone, the use of cheaper oyster-shell grit can further benefit small-holders in these countries. These benefits apart, simpler equipment suffices when designing and building a feed mixer on the farm, and transport costs are lower. If whole (unground) grain is used, the intake of which is accompanied by increased efficiency of feed utilisation, the costs of grinding, mixing and many of the handling procedures associated with mash and pellet preparation are eliminated. The choice feedstuffs can all be offered in the current feed distribution systems, either by mixing the ingredients first or by using a bulk bin divided into three compartments.

The medicine and epidemiology of bovine respiratory disease in feedlots

Bovine Respiratory Disease (BRD) results from a complex, multifactorial interaction of stressors, animal susceptibility, and respiratory pathogens. The infectious agents associated with BRD are ubiquitous among cattle populations. Typically, one or a combination of stressors are necessary to initiate BRD. Prevention of BRD should, therefore, address management procedures to minimise stressors. Administration of vaccines against BRD agents may help reduce the incidence of BRD but is unlikely to eliminate the condition. The effectiveness of antimicrobials in the treatment of BIRD depends primarily on early recognition and treatment. The use of antioxidant vitamins, minerals or other agents in the prevention and treatment of BRD warrants further research.

Use of complementary and alternative medicine and quality of life: changes at the end of life

The purpose of this study was to compare the physical, psychological and social dimensions associated with quality-of-life outcomes over the last year of life, between advanced cancer users and nonusers of complementary and alternative medicine. One hundred and eleven patients were identified through Queensland Cancer Registry records, and followed up every four to six weeks until close to death using standardized protocols. Outcome measures were symptom burden, psychological distress, subjective wellbeing, satisfaction with conventional medicine and need for control over treatment decisions. At the initial interview, 36 (32%) participants had used complementary/ alternative medicine the previous week; mainly vitamins, minerals and tonics and herbal remedies. Among all participants, 53 (48%) used at least one form of complementary/ alternative medicine over the study period. Only six (11%) visited alternative practitioners on a regular basis. Overall, complementary/ alternative medicine users reported higher levels of anxiety and pain, less satisfaction with conventional medicine and lower need for control over treatment decisions compared with nonusers. These differences tend to change as death approaches. A more rigorous assessment of complementary/ alternative medicine use, psychological distress, pain and subjective wellbeing among patients with advanced cancer is needed in the clinical setting.

Homocysteine-lowering therapy in renal disease

Hyperhomocysteinemia is a potential risk factor for vascular disease and is associated with endothelial dysfunction, a predictor of adverse cardiovascular events. Renal patients (end-stage renal failure (ESRF) and transplant recipients (RTR)) exhibit both hyperhomocysteinemia and endothelial dysfunction with increasing evidence of a causative link between the 2 conditions. The elevated homocysteine appears to be due to altered metabolism in the kidney (intrarenal) and in the uremic circulation ( extrarenal). This review will discuss 18 supplementation studies conducted in ESRF and 6 in RTR investigating the effects of nutritional therapy to lower homocysteine. The clinical significance of lowering homocysteine in renal patients will be discussed with data on the effects of B vitamin supplementation on cardiovascular outcomes such as endothelial function presented. Folic acid is the most effective nutritional therapy to lower homocysteine. In ESRF patients, supplementation with folic acid over a wide dose range ( 2 - 20 mg/day) either individually or in combination with other B vitamins will decrease but not normalize homocysteine. In contrast, in RTR similar doses of folic acid normalizes homocysteine. Folic acid improves endothelial function in ESRF patients, however this has yet to be investigated in RTR. Homocysteine-lowering therapy is more effective in ESRF patients than RTR.

Physical activity, exercise, and inflammatory markers in older adults: Findings from the health, aging and body composition study

OBJECTIVES: To examine the association between physical activity and inflammatory markers, with consideration for body fatness and antioxidant use. DESIGN: Cross-sectional study, using baseline data from the Health, Aging and Body Composition Study. SETTING: Metropolitan areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Black and white, well-functioning men and women (N=3,075), aged 70 to 79. MEASUREMENTS: Interviewer-administered questionnaires of previous-week household, walking, exercise, and occupational/volunteer physical activities. Analysis of covariance was used to examine the association between activity level and serum C-reactive protein (CRP), interleukin-6 (IL-6), and plasma tumor necrosis factor alpha (TNFalpha) with covariate adjustment. Antioxidant supplement use (multivitamin, vitamins E or C, beta carotene) was evaluated as an effect modifier of the association. RESULTS: Higher levels of exercise were associated with lower levels of CRP (P

Effects of LDL-immunoapheresis on plasma concentrations of vitamin E and carotenoids in patients with familial hypercholesterolemia

Recently very potent extracorporeal cholesterol-lowering treatment options have become available for patients with hypercholesterolemia. LDL immunoapheresis treatment selectively removes LDL and lipoprotein(a) from the circulation. Since LDL is the major carrier of lipophilic antioxidants in plasma, the purpose of the present study was to assess the effects of a single LDL apheresis treatment on plasma concentrations of tocopherols (alpha- and gamma-tocopherol) and carotenoids (alpha- and beta-carotene, zeaxanthin, cryptoxanthin, canthaxanthin, lycopene, and retinol). Plasma antioxidant concentrations were determined by HPLC in 7 patients with familial hypercholesterolemia before and after LDL immunoapheresis treatment. Plasma concentrations of both alpha- and gamma-tocopherol and the different carotenoids were significantly reduced by LDL apheresis. However, when standardized for cholesterol to adjust for cholesterol removal, alpha- and gamma-tocopherol, retinol, and the more polar carotenoids lutein and zeaxanthin increased in response to apheresis treatment, while the more unpolar carotenoids such as beta-carotene and lycopene did not change. These data demonstrate that a single LDL immunoapheresis treatment affects tocopherols and individual carotenoids differently. This may be explained by differences in chemical structure and preferential association with different lipoproteins. These results further imply that tocopherols, lutein, zeaxanthin, and retinol, are associated in part with lipoproteins and other carriers such as retinol-binding protein that are not removed during apheresis treatment. (C) 2004 Wiley-Liss, Inc.

The effect of the dietary supplement, Chitosan, on body weight: a randomised controlled trial in 250 overweight and obese adults

CONTEXT: Chitosan, a deacetylated chitin, is a widely available dietary supplement purported to decrease body weight and serum lipids through gastrointestinal fat binding. Although evaluated in a number of trials, its efficacy remains in dispute. OBJECTIVE: To evaluate the efficacy of chitosan for weight loss in overweight and obese adults. DESIGN AND SETTING: A 24-week randomised, double-blind, placebo-controlled trial, conducted at the University of Auckland between November 2001 and December 2002. PARTICIPANTS: A total of 250 participants (82% women; mean (s.d.) body mass index, 35.5 (5.1) kg/m(2); mean age, 48 (12) y). INTERVENTIONS: Participants were randomly assigned to receive 3 g chitosan/day (n = 125) or placebo (n = 125). All participants received standardised dietary and lifestyle advice for weight loss. Adherence was monitored by capsule counts. MAIN OUTCOME MEASURES: The primary outcome measure was change in body weight. Secondary outcomes included changes in body mass index, waist circumference, body fat percentage, blood pressure, serum lipids, plasma glucose, fat-soluble vitamins, faecal fat, and health-related quality of life. RESULTS: In an intention-to-treat analysis with the last observation carried forward, the chitosan group lost more body weight than the placebo group (mean (s.e.), -0.4 (0.2) kg (0.4% loss) vs +0.2 (0.2) kg (0.2% gain), P = 0.03) during the 24-week intervention, but effects were small. Similar small changes occurred in circulating total and LDL cholesterol, and glucose (P < 0.01). There were no significant differences between groups for any of the other measured outcomes. CONCLUSION: In this 24-week trial, chitosan treatment did not result in a clinically significant loss of body weight compared with placebo.

A prospective study of the use of alternative therapies by men with localized prostate cancer

Although the use of alternative therapies is highly prevalent amongst men with prostate cancer, research about the predictors of such use is limited. The current study aimed to describe prospectively the use of alternative therapies by men diagnosed with localized prostate cancer and identify predictors of alternative therapy use. In all, 111 men newly diagnosed with localized prostate cancer (93% response) were recruited to the study prior to treatment. Men's use of alternative therapies and psychological variables including: psychological distress, orientation to health care, decisional conflict, and health locus of control, were assessed at three time points-(1) before treatment; (2) 2 months after completion of treatment; and (3) 12 months after completion of treatment. Demographic information was also obtained. The percentage of men using alternative therapies was 25, 17 and 14% before treatment, 2 and 12 months after treatment, respectively. In general, the most commonly used therapies were dietary changes, vitamins and herbal and nutrient remedies. Alternative therapy use was not related to final treatment choices. Before treatment, men who used alternative therapies were more uncertain about prostate cancer compared to men who were not using these therapies. Men who were using alternative therapies 12 months after treatment were less psychologically distressed that men who were not using these therapies. Health locus of control and orientation to health care were not found to be related to men's use of alternative therapies. In conclusion, men's use of alternative therapies after localized prostate cancer varied across time in terms of the incidence of use, the types of therapies used, and the psychological correlates of therapy use. Informational support that targets uncertainty about prostate cancer may assist men at diagnosis who are considering alternative therapy use. The potential for alternative therapies to have a supportive function in patient care requires further investigation. (C) 2003 Elsevier Ireland Ltd. All rights reserved.