Medical Research Council study

Table 9.1 Medical Research Council study results...

At the conclusion of the Medical Research Council study, saturation tests were done on the subjects with long histories of accurately known ascorbic acid intakes. More than three daily test doses (10 mg/kg body weight) were necessary before a sharp rise occurred in urinary ascorbic acid excretion of subjects who had been receiving 20 mg/day or less, but again no distinction could be made in this way between the deficient and the protected individuals receiving the lower amounts. 

The studies described in this chapter have been supported by the Medical Research Council, the Leverhulme Trust and the Wellcome Trust. 

The medical statistician s role in regard to the investigation should be that of obstetrician, rather than morbid anatomist, for it is unfair to expect him to extract scientific knowledge by performing a kind of mathematical post mortem upon the numerical remains of a badly planned study. [Green FHK, Principle Medical Officer, Medical Research Council, The Lancet, 1954 ii 1084-1091.]... 

There are several possible reasons for the negative results of this trial. One possibility is that an insufficient amount of chemotherapy was administered. Few would argue that two cycles of chemotherapy is likely insufficient to eradicate microscopic metastatic disease. However, in a 975 patient trial conducted by the Medical Research Council and the European Organization for the Research and Treatment of Cancer, three cycles of CMV given prior to definitive therapy failed to provide the 10% improvement in survival that could have been detected by the trial (43). Similarly, other trials of neoadjuvant chemotherapy to date have similarly not shown any obvious improvement in survival (70-739, so it is unlikely that the number of cycles of therapy here had a significant impact on the outcome of the study. Even if more cycles could have had an impact, it should be remembered that this trial was stopped early because of chemotherapy-related treatment deaths with only two cycles of treatment. Others... 

MRC Vitamin Study Research Group (1991) Prevention of neural-tube defects results of the Medical Research Council Vitamin Study. Lancet 338 131-137. 

The author acknowledges the National Health and Medical Research Council of Australia, the Australian Research Council and The Wellcome Trust for financial support of his research on the molecular epidemiology of Echinococcus and echinococcosis. He would also like to thank numerous collaborators, especially Li Hua Zhang, Josephine Bowles, Robin Gasser, Thanh Hoa Le, David Blair, Mark Pearson and Mara Rosenzvit, for their significant contributions to the DNA studies. 

Studies from our laboratory were funded by the Medical Research Council (UK), the Wellcome Trust, the European Union, and the Royal Society. 

Acknowledgements. The costs of the studies were defrayed by grants from the Swedish Medical Research Council (3X-627 and 16X-3382). 

Abbreviations CA, carotid atherosclerosis CPIHD, Caerphilly Prospective Ischemic Heart Disease EVCS, Elderly Vitamin C Status IWHS-D, Lowa Women s Health Study MGH, Mortality in a Geriatric Hospital MRCT Medical Research Council Trial NAHNES I, National Health and Nutrition Examination Survey PSCHD, Prospective Study of vitamin C in Coronary Heart Disease SOP Supplementation... 

The Medical Research Council/British Heart Foundation study controlled the activity of antioxidants in the protection of a large group of patients (10,629) suffering from coronary disease who were treated daily with vitamin supplementation (vitamin E 600 mg, vitamin C 250 mg, and /3-carotene 20 mg). Similar high dosages were used in Age-Related Eye Disease Study (vitamin E 400 Ul, vitamin C 500mg, and /3-carotene 15 mg). In both studies the results were not positive. In these last two studies as in any of the studies reported in Table 9 the OS was measured to determine the real need of an antioxidant therapy. 

I 59 Fletcher AE, Breeze E, Shetty PS. Antioxidant vitamins and mortality in older persons finding from the nutrition add-on study to the Medical Research Council Trial of Assessment and Management of Older People in the Community. Am J Clin Nutr 2003 78 999-1010. 

The technique of randomization was pioneered in the field of agriculture (plants too show considerable individual variation) by Sir Ronald Fisher, a visionary statistician. It is generally acknowledged that the first randomized clinical trial, conducted in the 1940s, was a study evaluating the use of streptomycin in treating tuberculosis conducted by the (British) Medical Research Council Streptomycin in Tuberculosis Trials Committee. The results were published in the British Medical Journal in 1948. 

In the third example, a study of fellowships awarded by the Swedish Medical Research Council showed that the productivity of a woman candidate applying for the prestigious SMRC fellowship had to be 2.5 times more stellar to get the same competency score as the average male candidate.34... 

He pointed out that it had never been systematically evaluated, and that there were no studies that had attempted to control for these dramatic effects. A Medical Research Council funded randomised trial conducted in the United Kingdom in the 1950s appeared to support his conclusion when it found insulin coma produced no better outcome than a barbiturate-induced sleep used as a control procedure (Ackner, Harris, Oldham 1957). 

Studies in the laboratory of B. G. Hall have been supported by grants from the Medical Research Council of Canada, the National Institutes of Health, and the National Science Foundation, and by grants from the University of Connecticut and the University of Rochester. 

De Wit R, Roberts )T, Wilkinson PM et al. (2001) Equivalence of three or four cycles of bleomycin, etoposide and cisplatin chemotherapy and of a 3- or 5-day schedule in good prognosis germ cell cancer a randomised study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cooperative Group and the Medical Research Council. Journal of Clinical Oncology 19 1629-1640. 

There have been two major studies of ascorbate requirements in deple-tion/repletion studies, one in Sheffield during the 1940s (Medical Research Council, 1948) and the other in Iowa during the 1960s (Baker et al., 1969,1971 Hodges etal., 1969,1971). In addition, Kallnerand coworkers (1979,1981) have determined the body pool of ascorbate and the fractional rate of turnover under various conditions. Levine and coworkers (1995, 1996, 1999) have measured plasma and leukocyte ascorbate in studies of subjects maintained on more than minimally adequate amounts of vitamin C for relatively prolonged periods of time to determine optimum, rather than minimum, requirements. 

The minimum requirement for vitamin C was established in the Sheffield study (Medical Research Council, 1948), which showed that an intake of marginally less than 10 mg per day was adequate to prevent the development of scurvy or to cure the clinical signs. Results from the Iowa study (Baker et al., 1969,... 

The rate of ascorbate catabolism is not constant. If it were, more or less complete depletion of the body pool would be expected within 25 to 33 days yet, in the Sheffield study, in which the subjects were initially maintained on 70 mg of ascorbate per day, they received a diet essentially free from the vitamin no changes were apparent for 17 weeks (Medical Research Council, 1948). In the Iowa study, the subjects were not initially saturated with vitamin C the first skin lesions did not develop for 5 to 6 weeks after the depletion period (Baker etal., 1969,1971 Hodges etal., 1969,1971). Kallner and coworkers (1979) showed that the turnover time of body ascorbate varied between 56 days at low intake (about 15 mg per day) and 14 days (at intakes of 80 mg per day). It is thus apparent that the rate of ascorbate catabolism is affected markedly by the intake, and the requirement to maintain the body pool cannot be estimated as an absolute value. A habitual low intake, with a consequent low rate of catabolism, will maintain the same body pool as a habitual higher intake with a higher rate of catabolism. 

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