982 resultados para beneficial microbe
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Studies of ant-plant relationships elucidate how top-down effects of the third trophic level can affect the biomass, richness, and/or species composition of plants. Although widespread in the neotropics, few studies have so far examined the direct effects of ants on plant fitness. Here, through experimental manipulation (ant-exclusion) under natural conditions, we examined the effect of ant visitation to extrafloral nectaries on leaf herbivory and fruit set in Chamaecrista debilis in the Brazilian savanna. As opposed to other Chamaecrista species, our results showed that visiting ants (15 species) significantly reduce herbivory and increase fruit set by more than 50% compared to plants from which ants were excluded. This mutualistic system is facultative in nature, and corroborates the potential beneficial role of exudate-feeding ants as anti-herbivore agents of tropical plants. (C) 2010 Elsevier GmbH. All rights reserved.
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We investigate whether arterial baroreceptors mediate the training-induced blood pressure fall and resting bradycardia in hypertensive (SHR) and normotensive rats (WKY). Male SHR and WKY rats, submitted to sino-aortic denervation (SAD) or sham surgery (SHAM group), were allocated to training (T; 55% of maximal exercise capacity) or sedentary (S) protocols for 3 months. Rats were instrumented with arterial and venous catheters for haemodynamic measurements at rest (power spectral analysis) and baroreceptor testing. Kidney and skeletal muscles were processed for morphometric analysis of arterioles. Elevated mean arterial pressure (MAP) and heart rate (HR) in SHAM SHRS were accompanied by increased sympathetic variability and arteriolar wall/lumen ratio [+3.4-fold on low-frequency (LF) power and +70%, respectively, versus WKYS, P < 0.05]. Training caused significant HR (similar to 9% in WKY and SHR) and MAP reductions (-8% in the SHR), simultaneously with improvement of baroreceptor reflex control of HR (SHR and WKY), LF reduction (with a positive correlation between LF power and MAP levels in the SHR) and normalization of wall/lumen ratio of the skeletal muscle arterioles (SHR only). In contrast, SAD increased pressure variability in both strains of rats, causing reductions in MAP (-13%) and arteriolar wall/lumen ratio (-35%) only in the SHRS. Training effects were completely blocked by SAD in both strains; in addition, after SAD the resting MAP and HR and the wall/lumen ratio of skeletal muscle arterioles were higher in SHRT versus SHRS and similar to those of SHAM SHRS. The lack of training-induced effects in the chronic absence of baroreceptor inputs strongly suggests that baroreceptor signalling plays a decisive role in driving beneficial training-induced cardiovascular adjustments.
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Background: Inflammatory events antecede established renal injury in rats with 5/6 renal ablation (Nx), as indicated by the beneficial effects of early, uninterrupted treatment with mycophenolate mofetil (MMF). Angiotensin II also exerts a major pathogenic role at this initial phase. We investigated whether losartan (L) or L+MMF treatment, started early, and L+MMF treatment, started late, would exert lasting renoprotection in Nx even after being discontinued. Methods: Adult male Munich-Wistar rats underwent Nx and were divided into three groups: Nx (untreated), Nx(L) (given L), and Nx(LMMF) (given L and MMF). Protocol 1: treatments began on day 1, and ceased on day 30, after Nx. Protocol 2: L+MMF treatment began on day 30 and ceased on day 60. Results: Protocol 1: on day 30, hypertension, albuminuria and renal injury were strongly attenuated in Groups Nx(L) and Nx(LMMF). On day 120, these abnormalities were still attenuated in group Nx(LMMF). Protocol 2: on day 120, all parameters were similar between this late Nx(LMMF) group and untreated Nx. Conclusion: In Nx, temporary suppression of early, transitory hemodynamic/inflammatory phenomena affords relatively durable renoprotection even after treatment discontinuation. This effect is not obtained with similar temporary treatment initiated later in the course of renal disease. Copyright (C) 2010 S. Karger AG, Basel
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Study Design. Systematic Review. Objectives. To assess the effects of massage therapy for nonspecific low back pain. Summary of Background Data. Low back pain is one of the most common and costly musculoskeletal problems in modern society. Proponents of massage therapy claim it can minimize pain and disability, and speed return to normal function. Methods. We searched MEDLINE, EMBASE, CINAHL from their beginning to May 2008. We also searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, issue 3), HealthSTAR and Dissertation abstracts up to 2006. There were no language restrictions. References in the included studies and in reviews of the literature were screened. The studies had to be randomized or quasi-randomized trials investigating the use of any type of massage (using the hands or a mechanical device) as a treatment for nonspecific low back pain. Two review authors selected the studies, assessed the risk of bias using the criteria recommended by the Cochrane Back Review Group, and extracted the data using standardized forms. Both qualitative and meta-analyses were performed. Results. Thirteen randomized trials were included. Eight had a high risk and 5 had a low risk of bias. One study was published in German and the rest in English. Massage was compared to an inert therapy (sham treatment) in 2 studies that showed that massage was superior for pain and function on both short- and long-term follow-ups. In 8 studies, massage was compared to other active treatments. They showed that massage was similar to exercises, and massage was superior to joint mobilization, relaxation therapy, physical therapy, acupuncture, and self-care education. One study showed that reflexology on the feet had no effect on pain and functioning. The beneficial effects of massage in patients with chronic low back pain lasted at least 1 year after the end of the treatment. Two studies compared 2 different techniques of massage. One concluded that acupuncture massage produces better results than classic (Swedish) massage and another concluded that Thai massage produces similar results to classic (Swedish) massage. Conclusion. Massage might be beneficial for patients with subacute and chronic nonspecific low back pain, especially when combined with exercises and education. The evidence suggests that acupuncture massage is more effective than classic massage, but this need confirmation. More studies are needed to confirm these conclusions, to assess the impact of massage on return-to-work, and to determine cost-effectiveness of massage as an intervention for low back pain.
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Background-The effectiveness of heart failure disease management proarams in patients under cardiologists` care over long-term follow-up is not established. Methods and Results-We investigated the effects of a disease management program with repetitive education and telephone monitoring on primary (combined death or unplanned first hospitalization and quality-of-life changes) and secondary end points (hospitalization, death, and adherence). The REMADHE [Repetitive Education and Monitoring for ADherence for Heart Failure] trial is a long-term randomized, prospective, parallel trial designed to compare intervention with control. One hundred seventeen patients were randomized to usual care, and 233 to additional intervention. The mean follow-up was 2.47 +/- 1.75 years, with 54% adherence to the program. In the intervention group, the primary end point composite of death or unplanned hospitalization was reduced (hazard ratio, 0.64; confidence interval, 0.43 to 0.88; P=0.008), driven by reduction in hospitalization. The quality-of-life questionnaire score improved only in the intervention group (P<0.003). Mortality was similar in both groups. Number of hospitalizations (1.3 +/- 1.7 versus 0.8 +/- 1.3, P<0.0001), total hospital days during the follow-up (19.9 +/- 51 versus 11.1 +/- 24 days, P<0.0001), and the need for emergency visits (4.5 +/- 10.6 versus 1.6 +/- 2.4, P<0.0001) were lower in the intervention group. Beneficial effects were homogeneous for sex, race, diabetes and no diabetes, age, functional class, and etiology. Conclusions-For a longer follow-up period than in previous studies, this heart failure disease management program model of patients under the supervision of a cardiologist is associated with a reduction in unplanned hospitalization, a reduction of total hospital days, and a reduced need for emergency care, as well as improved quality of life, despite modest program adherence over time. (Circ Heart Fail. 2008;1:115-124.)
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Aims: We evaluated the effect of botulinum toxin type A (BTX-A) injections in the trigone on the antireflux mechanism and evaluated its short-term efficacy. Materials and Methods: Between April and December 2006, 21 patients (10 men and 11 women) were prospectively evaluated. All were incontinent due to refractory NDO and underwent detrusor injection of 300 units of BTX-A, including 50 units into the trigone. Baseline and postoperative evaluation after eight weeks included cystogram, urinary tract ultrasound and urodynamics. Results: At baseline, 20 patients had no vesicoureteral (VUR) and one had grade II unilateral VUR. Postoperative evaluation revealed no cases of de novo VUR and the patient with preinjection VUR had complete resolution of the reflux. Ultrasound showed 5 (23.8%) patients with hydronephrosis before BTX-A injection and only one (4.8%) at the followup evaluation (p=0.066). After treatment, 9 (42.8%) patients became dry, 11 (52.4%) were improved and one (4.8%) had no improvement. Improved patients received antimuscarinic treatment and 8 (38.1%) became dry, with a final total continence rate of 80.1%. Cystometric capacity increased from 271 +/- 92 to 390 +/- 1189 ml (p = 0.002), reflex volume varied from 241 +/- 96 to 323 +/- 201 ml (p = 0.020) and maximum detrusor pressure reduced from 66 +/- 39 to 38 +/- 37 cm H2O (p < 0.001). Conclusions: Our results confirm the safety of trigone injections of BTX-A in terms of development of VUR and upper urinary tract damage. Whether they are beneficial for patients with NDO or other causes of voiding dysfunction will need further studies.
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Background. Carbamazepine (Carba) is an anticonvulsant and psychotropic drug used widely for the treatment of intellectual disability and severe pains, but the incidence of hyponatremia is a common related occurrence. This hyponatremia is frequently attributed to a SIADH induced by this drug. It is also known that Carba is used to decrease the urinary volume in Diabetes Insipidus (DI) because it has an antidiuretic effect. Lithium (Li) is one of the most important drugs used to treat bipolar mood disorders. However Li has the undesirable capacity to induce DI. Nowadays, the association of these drugs is used in the treatment of patients with psychiatric and neurological problems. Methods. In vivo and in vitro (microperfusion) experiments were developed to investigate the effect of Carba in the rat Inner Medullary Collecting Duct (IMCD). Results. The results revealed that Carba was able to stimulate the V2 vasopressin receptor-Protein G complex increasing the water permeability (Pf) and water absorption. In vivo studies showed that in rats with lithium-induced DI, Carba decreased the urinary volume and increased the urinary osmolality. AQP2 expression was increased both in normal IMCD incubated with Carba and in IMCD from lithium-induced DI after Carba addition to the diet, when compared with the control. Conclusion. These results showed that the hyponatremia observed in patients using this anticonvulsant drug, at least in part, is due to the Carba capacity to increase IMCD`s Pf and that the Lithium-Carbamazepine association is beneficial to the patient.
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The role of physiological understanding in improving the efficiency of breeding programs is examined largely from the perspective of conventional breeding programs. Impact of physiological research to date on breeding programs, and the nature of that research, was assessed from (i) responses to a questionnaire distributed to plant breeders and physiologists, and (ii) a survey of literature abstracts. Ways to better utilise physiological understanding for improving breeding programs are suggested, together with possible constraints to delivering beneficial outcomes. Responses from the questionnaire indicated a general view that the contribution by crop physiology to date has been modest. However, most of those surveyed expected the contribution to be larger in the next 20 years. Some constraints to progress perceived by breeders and physiologists were highlighted. The survey of literature abstracts indicated that from a plant breeding perspective, much physiological research is not progressing further than making suggestions about possible approaches to selection. There was limited evidence in the literature of objective comparison of such suggestions with existing methodology, or of development and application of these within active breeding programs. It is argued in this paper that the development of outputs from physiological research for breeding requires a good understanding of the breeding program(s) being serviced and factors affecting its performance. Simple quantitative genetic models, or at least the ideas they represent, should be considered in conducting physiological research and in envisaging and evaluating outputs. The key steps of a generalised breeding program are outlined, and the potential pathways for physiological understanding to impact on these steps are discussed. Impact on breeding programs may arise through (i) better choice of environments in which to conduct selection trials, (ii) identification of selection criteria and traits for focused introgression programs, and (iii) identifying traits for indirect selection criteria as an adjunct to criteria already used. While many breeders and physiologists apparently recognise that physiological understanding may have a major role in the first area, there appears to be relatively Little research activity targeting this issue, and a corresponding bias, arguably unjustified, toward examining traits for indirect selection. Furthermore, research on traits aimed at crop improvement is often deficient because key genetic parameters, such as genetic variation in relevant breeding populations and genetic (as opposed to phenotypic) correlations with yield or other characters of economic importance, are not properly considered in the research. Some areas requiring special attention for successfully interfacing physiology research with breeding are discussed. These include (i) the need to work with relevant genetic populations, (ii) close integration of the physiological research with an active breeding program, and (iii) the dangers of a pre-defined or narrow focus in the physiological research.
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Introduction. Chronic allograft vasculopathy is an important cause of graft loss. Considering the inflammatory response in the development of chronic vascular lesions, therapeutic approaches to target the inflammatory process may be useful. We sought to investigate the possible protective effects on balloon catheter-induced vascular injury of thalidomide and tamoxifen, 2 drugs with powerful anti-inflammatory, immunomodulatory, and antifibrotic effects, using an animal model that mimics the morphologic features of chronic allograft vasculopathy. Methods. Male Wistar rats subjected to balloon catheter carotid injury (INJ) were treated with thalidomide (100 mg/kg), or tamoxifen (10 mg/kg), or vehicle. Contralateral right carotid arteries were used as uninjured controls. Morphometric and immunohistochemical analyses were performed at 14 days postinjury. Results. Injured carotid arteries showed marked neointimal hyperplasia, which was significantly inhibited among animals treated with thalidomide or tamoxifen: neointimal/media ratios of 1.4 +/- 0.4 versus 0.2 +/- 0.1 versus 0.4 +/- 0.2, for INJ, INJ + Thalid, and INJ + Tamox; respectively (P < .001). The endothelial cell loss was significantly less pronounced among animals subjected to carotid balloon injury that were treated with thalidomide (24 +/- 14 vs 1 +/- 1 cells per section in INJ, respectively (P < .05). Therapy with either thalidomide or tamoxifen effectively maintained alpha-smooth muscle actin expression in the media, similar to uninjured arteries. In this setting, tamoxifen was additionally effective to prevent the migration of myofibroblasts in to the intima. Conclusion. Thalidomide and tamoxifen were effective to reduce neointimal hyperplasia secondary to vascular damage. The vasculoprotective effects of thalidomide were more pronounced to preserve endothelial cells, whereas tamoxifen inhibited smooth muscle cell migration and proliferation. A possible beneficial effect of combined therapy with thalidomide plus tamoxifen should be addressed in future studies.
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GUALANO, B., V. DE. SALLES PAINNELI, H. ROSCHEL, G. G. ARTIOLI, M. NEVES JR, A. L. DE SA PINTO, M. E. DA SILVA, M. R. CUNHA, M. C. G. OTADUY, C. DA COSTA LEITE, J. C. FERREIRA, R. M. PEREIRA, P. C. BRUM, E. BONFA, and A. H. LANCHA JR. Creatine in Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial. Med. Sci. Sports Exerc., Vol. 43, No. 5, pp. 770-778, 2011. Creatine supplementation improves glucose tolerance in healthy subjects. Purposes: The aim was to investigate whether creatine supplementation has a beneficial effect on glycemic control of type 2 diabetic patients undergoing exercise training. Methods: A 12-wk randomized, double-blind, placebo-controlled trial was performed. The patients were allocated to receive either creatine (CR) (5 g.d(-1)) or placebo (PL) and were enrolled in an exercise training program. The primary outcome was glycosylated hemoglobin (Hb(A1c)). Secondary outcomes included the area under the curve of glucose, insulin, and C-peptide and insulin sensitivity indexes. Physical capacity, lipid profile, and GLUT-4 protein expression and translocation were also assessed. Results: Twenty-five subjects were analyzed (CR: n = 13; PL: n = 12). Hb(A1c) was significantly reduced in the creatine group when compared with the placebo group (CR: PRE = 7.4 +/- 0.7, POST = 6.4 +/- 0.4; PL: PRE = 7.5 +/- 0.6, POST = 7.6 +/- 0.7; P = 0.004; difference = -1.1%, 95% confidence interval = -1.9% to -0.4%). The delta area under the curve of glucose concentration was significantly lower in the CR group than in the PL group (CR = -7790 +/- 4600, PL = 2008 +/- 7614; P = 0.05). The CR group also presented decreased glycemia at times 0, 30, and 60 min during a meal tolerance test and increased GLUT-4 translocation. Insulin and C-peptide concentrations, surrogates of insulin sensitivity, physical capacity, lipid profile, and adverse effects were comparable between the groups. Conclusions: Creatine supplementation combined with an exercise program improves glycemic control in type 2 diabetic patients. The underlying mechanism seems to be related to an increase in GLUT-4 recruitment to the sarcolemma.
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The association of cyclophosphamide (CYC) and prednisone (PRED) for the treatment of lung fibrosis in systemic sclerosis (SSc) was only evaluated in uncontrolled studies, although in idiopathic interstitial lung disease (ILD) this association seems to be beneficial in patients with non-specific interstitial pneumonia (NSIP). Objectives: To treat SSc-ILD in a prospective open-label controlled study based on lung pattern during 12 months of treatment. Methods: A 3-year analysis was also performed. Twenty-four consecutive patients with SSc and ILD were submitted to an open lung biopsy. Eighteen patients (NSIP) were randomized in two groups: CYC versus CYC + PRED during 12 months. Lung function tests (diffusion lung capacity of monoxide carbone corrected for hemoglobin concentration (DLCO-Hb), forced vital capacity (FVC), total lung capacity) and Modified Rodnan Skin Score (MRSS) were performed before, after one of treatment and after 3 years from the end of the treatment. Results: Pulmonary function tests were similar in both groups on baseline. After 1 year of treatment, FVC% was comparable between CYC groups (p = 0.72) and in CYC + PRED (p = 0.40). Three years after the end of treatment, FVC% values (p = 0.39 in group CYC and p = 0.61 in CYC + PRED and p = 0.22 in CYC + PRED) and DLCO-Hb (p = 0.54 in CYC and p = 0.28 in CYC + PRED) were similar compared to 1 year of treatment. We observed a reduction of the MRSS in the CYC + PRED group after 1 year of treatment (p = 0.02); although after 3 years, MRSS values remained stable in both groups. Conclusions: CYC was effective to stabilize lung function parameters in NSIP lung pattern of SSc disease for 3 years after the end of a 1-year therapy.
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Objective. To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort. Methods. Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser). Results. Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6-98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P < 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6-11 months, 146 (12.8%) for 1-2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person-months of followup) were 3.85 (95% confidence interval [95% CI] 1.41-8.37), 2.7 (95% CI 1.41-4.76), and 0.54 (95% CI 0.37-0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18-4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39-0.99). Conclusion. Antimalarial drugs were shown to have a protective effect, possibly in a time-dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus.
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The balance between different immunological stimuli is essential in the progression and stabilization of atherosclerotic plaques. Immune regulation has been suggested as potential target for the treatment of atherosclerotic disease. We sought to determine whether treatment with pentoxifylline, a phosphodiesterase inhibitor with immunomodulating properties, could reduce the pro-inflammatory response observed in patients with acute coronary syndromes (ACS) and increase anti-inflammatory activity. In a double-blind, prospective, placebo-controlled study, 64 patients with ACS were randomized to receive pentoxifylline 400 mg TID or placebo for 6 months. Analysis of the pro-inflammatory markers, Greactive protein (CRP), interleukin (IL)-6, IL-12, interferon-gamma and tumor necrosis factor (TNF)-alpha and the anti-inflammatory cytokines, transforming growth factor (TGF)-beta 1 and IL-10 were done at baseline, 1 and 6 months. Pentoxifylline treatment significantly reduced the adjusted levels of CRP and TNF-alpha compared to placebo after 6 months (P=0.04 and P < 0.01, respectively). IL-12 increase was significantly less pronounced with pentoxifylline (P=0.04). The levels of the anti-inflammatory cytokine, IL-10, also declined significantly less in the pentoxifylline group compared to placebo (P < 0.01) with a trend towards a higher increase of TGF-beta 1 in the former group (P=0.16). Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory response in patients with ACS and may have beneficial clinical effects on cardiovascular events. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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Exercise is an effective intervention for treating hypertension and arterial stiffness, but little is known about which exercise modality is the most effective in reducing arterial stiffness and blood pressure in hypertensive subjects. Our purpose was to evaluate the effect of continuous vs. interval exercise training on arterial stiffness and blood pressure in hypertensive patients. Sixty-five patients with hypertension were randomized to 16 weeks of continuous exercise training (n=26), interval training (n=26) or a sedentary routine (n=13). The training was conducted in two 40-min sessions a week. Assessment of arterial stiffness by carotid-femoral pulse wave velocity (PWV) measurement and 24-h ambulatory blood pressure monitoring (ABPM) were performed before and after the 16 weeks of training. At the end of the study, ABPM blood pressure had declined significantly only in the subjects with higher basal values and was independent of training modality. PWV had declined significantly only after interval training from 9.44 +/- 0.91 to 8.90 +/- 0.96 m s(-1), P=0.009 (continuous from 10.15 +/- 1.66 to 9.98 +/- 1.81 m s(-1), P-ns; control from 10.23 +/- 1.82 to 10.53 +/- 1.97 m s(-1), P-ns). Continuous and interval exercise training were beneficial for blood pressure control, but only interval training reduced arterial stiffness in treated hypertensive subjects. Hypertension Research (2010) 33, 627-632; doi:10.1038/hr.2010.42; published online 9 April 2010
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Background-Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of beta-blockers in patients with Chagas cardiomyopathy. Methods and Results-We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and beta-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1+/-4.1 versus 26.3+/-5.1, P=0.001), smaller end-diastolic left ventricle diameter (6.7+/-1.0 mm versus 7.0+/-0.9 mm, P=0.001), smaller proportion of beta-blocker therapy (35.8% versus 68%, P<0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P=0.003). Twenty-four (35.8%) patients with Chagas disease were under beta-blocker therapy and had lower serum sodium (136.6+/-3.1 versus 138.4+/-3.1 mEqs, P=0.05) and lower body mass index (22.5+/-3.3 versus 24.9+/-4.3, P=0.03) compared with those who received beta-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under beta-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with beta-blockers was higher than that of patients without beta-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P=0.009) and beta-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P=0.044) were associated with better survival. Conclusions-Our study suggests that beta-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial.