Integrating research on thyroid cancer after Chernobyl--the Chernobyl Tissue Bank.

The only unequivocal radiological effect of the Chernobyl accident on human health is the increase in thyroid cancer in those exposed in childhood or early adolescence. In response to the scientific interest in studying the molecular biology of thyroid cancer after Chernobyl, the Chernobyl Tissue Bank was established. The project is supported by the governments of Ukraine and Russia, and financially supported (in total around US$3 million) by the European Commission, the National Cancer Institute of the USA and the Sasakawa Memorial Health Foundation of Japan. The project began collecting a variety of biological samples from patients on 1 October 1988, and has supplied material to 21 research projects in Japan, the USA and Europe. The establishment of the Chernobyl Tissue Bank has facilitated co-operation between these research projects and the combination of clinical and research data provides a paradigm for cancer research in the molecular biological age.

Investigation of loss of heterozygosity and SNP frequencies in the RET gene in papillary thyroid carcinoma.

In both medullary carcinoma and papillary carcinoma of the thyroid, altered expression of the RET gene is implicated in tumorigenesis. Recent studies suggest that loss of heterozygosity (LOH) at the G691S SNP may be associated with tumors from patients with a history of radiation exposure. We investigated LOH for three RET SNPs (G691S, S904S, and L769L) in tumor and normal tissue from 46 patients from Ukraine and Belarus who were exposed to radioactive fallout following the Chernobyl nuclear accident and were operated for papillary thyroid carcinoma between 1995 and 2000. Normal tissue from 28 patients was heterozygous for at least one SNP; DNA from the corresponding tumor samples was also heterozygous, indicating that no LOH had taken place. To assess SNP frequencies in a radiation-associated thyroid cancer cohort, we investigated a further 68 unpaired post-Chernobyl samples. For G691S, there was considerable deviation from Hardy-Weinberg equilibrium; more detailed analysis showed that this was linked to age at onset of disease. Among younger patients, the distribution of genotypes conformed to Hardy-Weinberg equilibrium; among older patients, we observed marked deviation (p = 0.0072), with significant over-representation of the rare S allele relative to the younger groups (Fisher's exact, p = 0.0233). This suggests that SNPs in the RET oncogene may play a role in sporadic papillary thyroid carcinoma.

Comparison of continuous infusion versus midwife administered top-ups of epidural bupivacaine for labour analgesia: effect on second stage of labour and mode of delivery.

Using a population-based study we retrospectively compared the effect of continuous versus intermittent top-up epidural analgesia on the outcome of labour at the University Hospital of Wales. We analysed the labour outcome of 410 primigravid deliveries over an 18-month period during a change in delivery suite protocol. Data were retrieved from the Cardiff Births Survey and the sample was analysed in two groups: group 1 (n = 201) received a continuous infusion of 0.1% bupivacaine plus fentanyl 2 microg/mL and group 2 (n = 209) received intermittent top-ups of the same solution. Outcome measures were the number of operative deliveries and the proportion of those deliveries that were due to prolongation of the second stage of labour. There were no significant differences in terms of group characteristics, women undergoing assisted vaginal delivery (group 1: 83 vs. group 2: 70, OR 0.8 CI 0.5-1.2), caesarean section (group 1: 59 vs. group 2: 61, OR 1.0 CI 0.6-1.5), and women with prolonged second stage (group 1: 50 vs. group 2: 47, OR 1.1 CI 0.6-1.8). The presumed reduction in motor blockade associated with intermittent top-up epidural regimes did not affect the outcome of labour.

Body size and subcutaneous fat patterning in adolescence.

Factors that influence low birth weight at term may also be associated with subcutaneous fat patterning in later life. This hypothesis was investigated in a comparative (retrospective) cohort study. The subjects, born in Cardiff between 1975 and 1977, were of mean age 15.7 years. Cases (low birth weight (< 2500 g) at term) were matched with controls (normal birth weight (3000-3800 g) at term) for sex, parity, place of birth, date of birth, and gestation. Subscapular skinfold (an index of central subcutaneous fat) and triceps skinfold (an index of peripheral subcutaneous fat) were measured using a Holtain skinfold caliper. The differences (cases minus controls) (95% confidence interval) for subscapular and triceps skinfolds were respectively -0.3 mm (-1.74 to 1.14) and -0.48 mm (-1.75 to 0.79). These findings are inconsistent with the hypothesis that low birth weight at term is associated with subcutaneous fat patterning in adolescence.

Birth weight at term and lung function in adolescence: no evidence for a programmed effect.

It has been suggested that factors which influence low birth weight at term may be associated with reduced lung function in later life. This hypothesis was investigated in a comparative (retrospective) cohort study of 164 matched pairs of subjects where the observers responsible for tracing and studying the subjects were unaware of their case or control status. The subjects, born in Cardiff between 1975 and 1977, were of mean age 15.7 years. Cases (low birth weight (< 2500 g) at term) were matched with controls (normal birth weight (3000-3800 g) at term) for sex, parity, place of birth, date of birth, and gestation. Lung function was measured using a portable spirometer. The corrected mean differences (95% confidence interval) in forced vital capacity (FVC) and flow when 50% or 25% of the FVC remains in the lungs between the cases and controls were respectively -41 ml (-140 to 58), -82 ml/sec (-286 to 122), and -83 ml/sec (-250 to 83). None of these differences were statistically significant. These results are inconsistent with the hypothesis that low birth weight at term is associated with reduced lung function in adolescence.

Relation between birth weight at term and systolic blood pressure in adolescence.

OBJECTIVE: To examine whether birth weight is related to systolic blood pressure during adolescence. DESIGN: Retrospective (comparative) cohort study. The observers who traced and studied the subjects were unaware of their case-control status. SUBJECTS: 330 subjects were born in Cardiff in 1975-7. Cases who were low birth weight at term (< 2500 g) were matched with controls of normal birth weight (3000-3800 g) at term. MAIN OUTCOME MEASURES: Systolic blood pressure measured by random zero sphygmomanometry in the subject's right arm with the subject supine, corrected for size and age. RESULTS: The mean age at examination was 15.7 years. The mean systolic blood pressure of the cases was 105.8 mm Hg and of the controls 107.5 mm Hg. The corrected difference (95% confidence interval) in systolic blood pressure between the cases and controls was 1 mm Hg (-3 to +1 mm Hg; two tailed probability 0.33). CONCLUSION: Systolic blood pressure in adolescents of low birth weight is not significantly different from that of adolescents of normal birth weights.

Adjusting anticoagulation to prosthesis thrombogenicity and patient risk factors. Recommendations for the Medtronic Hall valve.

In order to determine optimum anticoagulation levels for the Medtronic Hall valve, the effect of low anticoagulation (mean International Normalized Ratio [INR] 2.5, 1979-1984) and moderate anticoagulation (mean INR 3.0, 1985-1989) was determined in 345 patients (183 low, 162 moderate) undergoing isolated mitral valve replacement (MVR) and 241 patients (91 low, 150 moderate) undergoing isolated aortic valve replacement (AVR). There were no cases of valve thrombosis. Embolic events and bleeding events were graded in severity and multiple decrement event-free survival calculated according to valve site and anticoagulation level: MVR low, MVR moderate, AVR low, and AVR moderate. In the MVR low group, 80% were free of all events and 93% free of serious events at 3 years compared with 89% and 98%, respectively, in the MVR moderate group. The AVR low group experienced a very small incidence of embolic events (one only) and no bleeding events. The AVR moderate group suffered more bleeding and more embolic events and at 3 years only 87% were event-free compared with 99% in the AVR low group. In both AVR groups, all embolic events were associated with one or more known stroke risk factors. Patients under 70, in sinus rhythm who were normotensive and were nonsmokers suffered no embolic events irrespective of their anticoagulation level. We conclude that the optimum INR for the average Medtronic Hall patient is 3.0 after MVR and 2.5 after AVR but some adjustments may be required in relation to stroke risk factor analysis.