Clinical Trial Service Unit

About: Clinical Trial Service Unit is a based out in . It is known for research contribution in the topics: Population & Stroke. The organization has 428 authors who have published 1387 publications receiving 181920 citations.

Cancer and the immortal strand hypothesis.

Abstract: THE main causes of mortality in the Western world are largely a matter of somatic genetics. As we age, our cells accumulate more and more mutations. Eventually one of them acquires a set of changes in phenotype that allows it to generate an expanding clone of descendants, causing an atheromatous plaque in an artery or an invasive cancer. These changes are the result of a cumulative process extending throughout our life, as is demonstrated in the relation between smoking and lung cancer and between pregnancy and breast cancer. Someone who started smoking at the age of 15 will, when 65, have a higher risk of lung cancer than someone who started at 20, showing that lungs can store for half a century the damage acquired in your teenage years (Doll and Peto 1981). Conversely, because pregnancy protects somewhat against the subsequent risk of breast cancer, a woman who first became pregnant when 13 will, when 70, have a lower risk of breast cancer than a woman whose first pregnancy was in her 20s, showing that the latter was accumulating risk as a teenager (MacMahon et al. 1973). Long-lived animals protect themselves from the physical and chemical dangers of their environment by continuous replacement of the cells on their external surfaces and it is in these sites of continuous cell division that most human cancers arise. An adult human contains ∼1012 rapidly multiplying cells. During a life span of ∼30,000 days, each of us makes and discards from skin, gut, and certain internal organs such as lymph glands and bone marrow about one-third of these cells each day (Potten and Morris 1988). If all these 1012 cells divide every third day, the cells remaining after 80 years would each have had ∼10,000 successive divisions in their ancestry. So by the age of 80, given a mutation rate of ∼10−6/gene/replication (Drake 1999), 1 in 100 of the copies of each gene would be mutant. In a collection of 1012 cells, 1010 would have a mutant copy of any particular gene, 108 would have mutations in any pair of genes, and a million would have mutations in any trio of genes. Nevertheless, despite there being many combinations of mutant genes that can trigger cancer (Hahn and Weinberg 2002), most people never develop cancer. So there must be some feature of multicellular systems that slows the rate of accumulation of replication errors.

Three-year follow-up of the Oxford Cholesterol Study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study

Abstract: We report the results of a randomized single-centre study designed to assess the effects of simvastatin on blood lipids, blood biochemistry, haematology and other measures of safety and tolerability in preparation for a large-scale multicentre mortality study. Six hundred and twenty-one individuals considered to be at increased risk of coronary heart disease were randomized, following a 2-month placebo 'run-in' period, to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. Their mean age was 63 years, 85% were male, 62% had a history of prior myocardial infarction (MI), and the mean baseline total cholesterol was 7.0 mmol.l-1. Median follow-up in the present report is 3.4 years. Eight weeks after randomization, 40 mg daily simvastatin had reduced non-fasting total cholesterol by 29.2% +/- 1.1 (2.03 +/- 0.08 mmol.l-1) and 20 mg daily simvastatin had reduced it by 26.8% +/- 1.0 (1.87 +/- 0.07 mmol.l-1). Almost all of the difference in total cholesterol at 8 weeks was due to the reduction in LDL cholesterol (40.8% +/- 1.6 and 38.2% +/- 1.4 among patients allocated 40 mg and 20 mg of simvastatin daily respectively), but simvastatin also reduced triglycerides substantially (19.0% and 17.3%) and produced a small increase in HDL cholesterol (6.4% and 4.8%). These effects were largely sustained over the next 3 years, with 40 mg daily simvastatin producing a slightly greater reduction in total cholesterol at 3 years (25.7% +/- 1.9 reduction) than did 20 mg daily simvastatin (22.2% +/- 1.8). There were no differences between the treatment groups in the numbers of reports of 'possible adverse effects' of treatment or of a range of different symptoms or conditions (including those related to sleep or mood) recorded at regular clinic follow-up. Mean levels of alanine aminotransferase, aspartate aminotransferase and creatine kinase were slightly increased by treatment, but there were no significant differences between the treatment groups in the numbers of patients with significantly elevated levels. A slightly lower platelet count in the simvastatin group was the only haematological difference from placebo, with no difference in the numbers of patients with low platelet counts. In summary, the simvastatin regimens studied produced large sustained reductions in total cholesterol, LDL cholesterol and triglyceride and small increases in HDL cholesterol. They were well tolerated, with no evidence of serious side-effects during the first 3 years of this study.(ABSTRACT TRUNCATED AT 400 WORDS)

Part II: Cancer in Indigenous Africans—causes and control

Abstract: Summary Africa has contributed substantial knowledge to the understanding of certain risk factors for cancer, such as the role of several infectious agents (eg, viruses, bacteria, and parasites), aflatoxins, and certain lifestyle factors. Although the relative importance of many lifestyle factors is becoming better understood in developed countries, more work is needed to understand the importance of these factors in different African settings. In view of the substantial genetic diversity in Africa, it would be prudent not to generalise too widely from one place to the next. We argue that risks for several exposures related to certain cancers differ from the patterns seen in developed countries. In this paper, we review the current knowledge of causes of some of the leading cancers in Africa, namely cancers of the cervix, breast, liver, prostate, stomach, bladder, and oesophagus, Kaposi's sarcoma, non-Hodgkin lymphoma, and tobacco-related cancers. There are no comprehensive cancer-control programmes in Africa and provision of radiotherapy, chemotherapy, and palliation is inadequate. Certain cost-effective interventions, such as tobacco control, provision of antiretroviral therapy, and malarial and bilharzial control, can cause substantial decreases in the burden of some of these cancers. Vaccinations against hepatitis B and oncogenic human papilloma viruses can make the biggest difference, but very few countries in Africa can afford these vaccines without substantial subsidisation.

Dietary vitamin C intake and lung function in rural China

Abstract: The relation between dietary vitamin C intake and pulmonary function was investigated in a cross-sectional study carried out in 69 counties in rural China in 1989. Within each of the 69 counties, 120 subjects aged 35-64 years were identified using a three-stage random clustering procedure. Each subject underwent pulmonary function testing, completed a detailed questionnaire, and provided a blood sample. Dietary vitamin C intakes were estimated among half of the subjects using a 3-day weighed record of household food intake. Plasma vitamin C was measured in sex-specific blood pools created from individual samples in each geographic area. Among the 3,085 subjects for whom there were complete data, dietary intake of vitamin C (151 mg/day (standard deviation, 111)) was significantly related to forced expiratory volume in the first second (FEV 1 ) and forced vital capacity after adjustment for sex, age, height, weight, total caloric intake, tobacco smoking, and education. An increase of 100 mg/day in vitamin C intake was associated with an increase of 21.6 ml (95% confidence interval -0.4 to 43.5) in FEV 1 and an increase of 24.9 ml (95% confidence interval 0.2 to 49.6) in forced vital capacity. No significant interaction with smoking status was observed. A significant positive association was also observed at the geographic level, between county-pooled plasma vitamin C and mean FEV 1 . These data support the hypothesis that dietary vitamin C may protect against the loss of pulmonary function.