The genetic basis of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. Familial clustering of cases suggests that genetic factors play an important part in its aetiology. A number of studies of families with several cases of PCOS have produced results suggesting an autosomal dominant trait. Detailed analysis of a large number of affected families has, however, cast some doubt about the mode of inheritance. An autosomal dominant trait remains possible but a more complex aetiology seems more likely. The results of our recent studies support the concept of an oligogenic disorder in which genes affecting metabolic pathways in glucose homeostasis and steroid biosynthesis are both involved. We review evidence for an important role for the insulin gene minisatellite in the aetiology of anovulatory PCOS and for the gene coding for P450 cholesterol side chain cleavage (CYP11a) in the mechanism of excessive androgen secretion in women with polycystic ovaries. We propose that the heterogeneity of clinical and biochemical features in PCOS can be explained by the interaction of a small number of key genes with environmental, particularly nutritional, factors.      

Costs of neonatal care for low-birthweight babies in English hospitals

Aim:  To estimate mean costs of neonatal care for babies with birthweights ≤1800 g in a regional Level 3 unit and three Level 2 units providing short-term intensive care.
Method:  Babies ≤1800 g admitted to units in four hospitals in England over 15 months in 2001–2002 were audited until discharge. Unit costs (2005–2006 prices) were attributed to their resource items, including neonatal cot occupancy, pharmaceuticals, blood products and ambulance transfers. Bootstrapped mean costs were derived for the Level 3 unit and the Level 2 units combined.
Results:  The mean gestation period for 199 Level 3 babies was 29.5 weeks compared with 30.4 weeks for 192 Level 2 babies (p = 0.003). Mean costs excluding ambulance journeys were £17  861 per Level 3 baby and £12  344 per Level 2 baby. Level 3 babies <1000 g averaged £26  815, whereas Level 2 babies <1000 g were generally less costly than babies 1000–1499 g. Ambulances transported 76 Level 3 babies and 62 Level 2 babies; their adjusted mean costs were £18  495 and £12  881, respectively.
Conclusion:  By comprehensively costing resource components, the magnitude of total costs for low-birthweight babies has been revealed, thus demonstrating the importance of budgets for neonatal units being realistically determined by commissioners of neonatal services.     

Vitamin K status in cystic fibrosis

Appearance of PIVKA-II (protein induced by vitamin K absence-II) in serum is a biochemical sign of insufficient vitamin K-dependent carboxylation of prothrombin. Plasma concentrations of PIVKA-II and vitamin K1 were determined in 24 children with cystic fibrosis. Eight were supplemented with vitamin K1. The purpose of the study was to determine the occurrence of vitamin K deficiency in cystic fibrosis and to evaluate the effect of vitamin K supplementation. PIVKA-II was detectable in only one unsupplemented child. In this patient, the concentration of vitamin K1 was below the limit of detection of 60 ng/l. Vitamin K1 levels in the other unsupplemented children were normal (mean 476 ng/l = 1 mmol/l). The supplemented patients showed extremely high levels of vitamin K1 (mean 22445 ng/l = 50 nmol/l). In conclusion, vitamin K deficiency occurs infrequently in cystic fibrosis. Checking the coagulation system is advised, but routine vitamin K supplementation is not recommended. If additional vitamin K is needed, the starting dose should not exceed 1 mg daily.     

Physical activity and coronary heart disease in older adults. A systematic review of epidemiological studies

BACKGROUND: While there is good evidence to suggest an inverse relation of physical activity and cardiorespiratory fitness with coronary heart disease (CHD) in middle-aged men and women, much less is known about this association in older adults. The purpose of this paper was to explore the relation of physical activity and cardiorespiratory fitness with CHD in older adults by reviewing relevant studies. METHODS: Publications were identified in two ways: i) conducting a PUBMED search from its inception in 1966 until January 2001; and ii) scrutinizing the reference sections of identified papers. RESULTS: Ten studies relating physical activity and two relating cardiorespiratory fitness in older people to CHD met the inclusion criteria. With one exception, the studies were observational in nature and the majority of these were of prospective cohort design. Most studies featured men only. Of the eleven studies that presented data on older men, eight reported an inverse relation between physical activity or cardiorespiratory fitness and CHD, and statistical significance was seen in five of these. There were too few data on older women to draw clear conclusions regarding the association in this group. CONCLUSIONS: This review suggests that, in older adult men, physical activity and cardiorespiratory fitness are inversely related to CHD risk. This association is unlikely to be attributable to reverse causality or confounding. Except where such advice is contraindicated, older adult men may benefit from physical activity in terms of reduced CHD risk.     

Sexual precocity: sex incidence and aetiology

The aetiology of 197 girls and 16 boys presenting with sexual precocity was reviewed. Ninety one girls and four boys had central precocious puberty (M:F 23:1); a cause was identified in all the boys but in only six girls. All boys with precocious puberty need detailed investigation; in girls investigation should be based on clinical findings, particularly the consonance of puberty.