Adiposity and physical activity as predictors of cardiovascular mortality.

OBJECTIVE: To investigate whether cardiovascular mortality related to obesity could be modified by physical activity. DESIGN: Mortality follow-up. SETTING: Population study. PARTICIPANTS: Participants in a health survey: 34 868 women and 32 872 men free from known cardiovascular disease or diabetes at baseline. MAIN OUTCOME MEASURES: Total cardiovascular mortality. MAIN RESULTS: During 16 years of follow-up, 3026 women and 3526 men had died from cardiovascular causes. In middle age, obesity [body mass index (BMI) of 30 or higher] was associated with increased risk of cardiovascular death, but the association weakened with age. After 70, there was no association between BMI and cardiovascular death. At all ages, a lower level of physical activity was associated with a higher cardiovascular mortality. In women with high physical activity, indicated by at least 30 min of moderate to vigorous activity more than once a week, cardiovascular mortality was only slightly higher in the obese compared to lean women (adjusted relative risk, 1.27; 95% confidence interval, 0.80-2.00). In men with high physical activity, cardiovascular mortality was, however, significantly higher among the obese (relative risk, 1.62; 95% confidence interval, 1.09-2.40). In both genders cardiovascular mortality was substantially higher in obese people who reported no regular physical activity compared to obese people with a high level of physical activity. CONCLUSION: In obese women, being highly active may, to a large extent, compensate for the risk-increasing effect of being obese, whereas in obese men who engage in a high level of physical activity, the risk of cardiovascular death may be higher than in lean and equally active men.     

The changing survival profile of people with Down's syndrome: implications for genetic counselling

Cohort studies have indicated that the survival of individuals with Down's syndrome has dramatically increased over the past 50 years. Early childhood survival in particular has shown major improvement, due largely to advances in cardiac surgery and in general health management. The present study was based on a continuous cohort of 1332 people with Down's syndrome in Western Australia, registered for intellectual disability services between 1953 and 2000. Their life expectancy was 58.6 years, 25% lived to 62.9 years, and the oldest living person is 73 years of age. Life expectancy for males was greater than females by 3.3 years. The substantial increase in survival across the study period means that the life expectancy of people with Down's syndrome is approaching that of the general population, but accompanied by a range of significant mid-life health problems. The findings are of relevance to all developed countries and have considerable implications in terms of the counselling information provided to families at risk of having a child with Down's syndrome.     

A purine-rich DNA sequence motif present in SV40 and lymphotropic papovavirus binds a lymphoid-specific factor and contributes to enhancer activity in lymphoid cells

The enhancer of simian virus 40 (SV40) is active in a wide variety of tissues and hosts and thus has been called a general enhancer. Previous work has established that this region contains a number of subsegments, each with a different cell type specificity. By analyzing enhancer deletion mutants of SV40 with a restricted cell type specificity, we have identified a purine-rich DNA motif (Pu box) that is essential for activity of the mutant enhancer in lymphoid cells and also obtained evidence for an independent element that confers activity in kidney CV-1 cells. The Pu box element is positively regulated since binding of a cognate factor(s) was only observed in lymphoid cell extracts. The Pu box is also present in the 63-bp enhancer repeat of lymphotropic papovavirus (LPV), and competition experiments show that the SV40 and LPV sequences bind the same factor(s). Thus, the Pu box is likely to be a major determinant of the lymphotropic host range of LPV. In SV40, however, the Pu box is one of several enhancer elements with different cell specificities. We suggest that such an arrangement reflects a diversification strategy of SV40 to maximize its chance of adaptation to various types of host cells.     

Extraskeletal myxoid chondrosarcoma: multimodal diagnosis and identification of a new cytogenetic subgroup characterized by t(9;17)(q22;q11)

Extraskeletal myxoid chondrosarcoma is a rare malignant soft tissue tumour that can be difficult to diagnose correctly, especially preoperatively. We describe four cases of extraskeletal myxoid chondrosarcoma of the extremities diagnosed by a multimodal approach. The cytological examination of fine-needle aspirates showed small and round, mildly pleomorphic cells lying in sheets and cords, but also dispersed within a myxoid and metachromatic intercellular substance. Histological, electron microscopic and immunocytochemical examination also yielded findings compatible with the diagnosis of extraskeletal myxoid chondrosarcoma. Cytogenetic analysis demonstrated a t(9;22)(q22;q12) in two tumours and a t(9;17)(q22;q11) in the third and fourth. The translocation t(9;22)(q22;q12) has been described repeatedly in extraskeletal myxoid chondrosarcoma but never in other tumours; hence, the detection of this pathognomonic chromosome abnormality in short-term cultured cells from fine-needle aspirates verified the diagnosis in two of the cases. The t(9;17)(q22;q11) found in the last two cases probably represents a new cytogenetic subgroup of extraskeletal myxoid chondrosarcoma as it, too, is unknown in other contexts. The multimodal approach taken in these four cases enabled a definite diagnosis of a rare malignant tumour whose cytological and histological features alone are usually not sufficiently distinct to rule out other differential diagnostic possibilities. Received: 16 March 1999 / Accepted: 1 June 1999     

Medical aspects of school-aged children with Down syndrome

Current and comprehensive information about the medical issues affecting children with Down syndrome (DS) is of value in counselling parents who are considering prenatal diagnosis and in planning services for people with DS as they age, especially given the continued improvements in their survival. Parents of school-aged children (mean age 11.37 years, 57.3% male, 42.7% female) with DS were identified by linking registers from the Disability Services Commission and the Birth Defects Registry. Less than half the children had cardiac and bowel conditions. More than half had ear conditions and more than three quarters had eye conditions. Ear, nose, and throat professionals were the specialists seen most often and the rate of tympanostomy tube insertion was nearly 17 times that of the general childhood population. Children with DS were over five times more likely to wear glasses than other children. These findings suggest that chronic, non life-threatening conditions impose a burden on families but do not threaten quality of life.     

The prevalence of respiratory symptoms and asthma among school children in three different areas of Norway

The role of exposure to ambient air pollution has been a topic of interest as a potential risk factor for respiratory symptoms and asthma. We expected that the prevalence rates would vary in Norway between the capital, Oslo, the mountainous area Hallingdal and the industrial area Odda. Surveys were conducted in school children, aged 6-16 years, in; Oslo (n=2577), Hallingdal (n=1177) and Odda (n=831). The parent-reported prevalence of wheeze in past year was almost similar in Oslo (13. 1 (95% CI 11. 7-14. 5)) and Upper Hallingdal (14. 2 (13. 1–15. 3)), but lower in Odda (9. 0 (7. 0–11. 0)). The findings for severe respiratory symptoms were almost equal. The age patters within each area differed. The risk of wheeze ever (p < 0.001) and wheeze in past year (p=0.04) decreased with increasing age in Odda, while there was an increase in the risk of exercise induced wheeze in Oslo (p=0.02) and Hallingdal (p < 0.001). The lifetime prevalence of asthma was lowest in Odda (5. 4 (3. 8–7. 0)) compared to Oslo (9. 4 (8. 2–10. 6)) and Hallingdal (8. 5 (6. 8–10. 2)). There was a positive association between physical activity and wheeze in past year. The results do not support the hypothesis that respiratory morbidity is more common in urban than rural areas, age and physical activity can influence the prevalence rates of respiratory symptoms in school children.     

Mortality in 497 patients with affective disorders attending a lithium clinic or after having left it

The impact of lithium prophylaxis on mortality has been studied in 497 patients, 405 bipolars and 92 unipolars, who attended the same out-patient lithium clinic for up to 30 years. In order to avoid preselection, no minimum period of lithium treatment was required in our study. Of a total of 6014 patient-years, 4330 were spent in regular contact with the study clinic. General mortality due to natural causes was not significantly increased; among cardiovascular diseases, only pulmonary embolism showed an excess mortality. No patients died of lithium intoxication or chronic renal insufficiency. Patients were divided into three groups: Group A, 277 patients, attended the study clinic until death or the end of the study, Group B, 86 patients, left the clinic but continued to take lithium, and Group C, 134 patients, both left the clinic and stopped taking lithium. Among bipolars, the suicide rate compared to the general population was in excess in all three groups. Among unipolars, suicides occurred only after the patients had left the study clinic and stopped taking lithium. A special analytical method was used for intergroup comparisons of suicide rates. Bipolars in Group A attending the study clinic regularly had a suicide rate of 3.5 per 1000 patient-years. The rate increased to 6.3 or by 80 % if patients had left the clinic and did not take lithium any longer as in Group C. The suicide rate in Group C increased by 45% compared to Group B, patients who left the clinic but continued to take lithium. Our results support the hypothesis that lithium has a significant antisuicidal effect in bipolars as well as in unipolars. The suicide mortality can be further reduced by regular attendance in a specialised mood disorder clinic.