Use of 'sham' radiotherapy in randomized clinical trials

The objective of this systematic review was to identify quality trials that use sham radiotherapy in their design and review them to determine its potential value. The Cochrane Library, Pubmed and a Reference Search served as data sources. Trials were included if they met a minimum quality score of 3 on a validated assessment instrument (which assesses randomization, control and blinding) and if they compared sham radiotherapy to active treatment. External beam therapy and brachytherapy trials were considered. Twenty-six trials were identified, collectively including 2663 participants in the period of 1970-2004. All the trials studied the value of radiotherapy for treatment or prevention of benign diseases, including multiple sclerosis, coronary artery restenosis, age-related macular degeneration and Graves' ophthalmopathy. There were no trials relating to the use of radiotherapy in the treatment of malignancy. This review showed that it is possible to carry out sham radiotherapy with due regard for ethical concerns, with effective blinding and high levels of patient acceptance. Large sample sizes with multicentre trial designs were achievable. Although the statistical philosophy for using sham radiotherapy in trials is legitimate, it is no longer routinely used

Folate Deficiency Is Associated With Oxidative Stress, Increased Blood Pressure, and Insulin Resistance in Spontaneously Hypertensive Rats

BACKGROUND: The role of folate deficiency and associated hyperhomocysteinemia in the pathogenesis of metabolic syndrome is not fully established. In the current study, we analyzed the role of folate deficiency in pathogenesis of the metabolic syndrome in the spontaneously hypertensive rat (SHR). METHODS: Metabolic and hemodynamic traits were assessed in SHR/Ola rats fed either folate-deficient or control diet for 4 weeks starting at the age of 3 months. RESULTS: Compared to SHRs fed a folate-replete diet, SHRs fed a folate-deficient diet showed significantly reduced serum folate (104±5 vs. 11±1 nmol/L, P < 0.0005) and urinary folate excretion (4.3±0.6 vs. 1.2±0.1 nmol/16h, P < 0.0005) together with a near 3-fold increase in plasma total homocysteine concentration (4.5±0.1 vs 13.1±0.7 μmol/L, P < 0.0005), ectopic fat accumulation in liver, and impaired glucose tolerance. Folate deficiency also increased systolic blood pressure by approximately 15mm Hg (P < 0.01). In addition, the low-folate diet was accompanied by significantly reduced activity of antioxidant enzymes and increased concentrations of lipoperoxidation products in liver, renal cortex, and heart. CONCLUSIONS: These findings demonstrate that the SHR model is susceptible to the adverse metabolic and hemodynamic effects of low dietary intake of folate. The results are consistent with the hypothesis that folate deficiency can promote oxidative stress and multiple features of the metabolic syndrome that are associated with increased risk for diabetes and cardiovascular disease