Lancet
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Osteogenesis imperfecta is a genetic disorder of increased bone fragility, low bone mass, and other connective-tissue manifestations. The most frequently used classification outlines four clinical types, which we have expanded to seven distinct types. In most patients the disorder is caused by mutations in one of the two genes encoding collagen type 1, but in some individuals no such mutations are detectable. ⋯ However, at present, the best treatment regimen and the long-term outcomes of bisphosphonate therapy are unknown. Although this treatment does not constitute a cure, it is an adjunct to physiotherapy, rehabilitation, and orthopaedic care. Gene-based therapy presently remains in the early stages of preclinical research.
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Experimental data suggest that nitric oxide (NO) generated from neuronal NO synthase (nNOS) modulates the myocardial inotropic state. To assess the contribution of NO, derived from endothelial and neuronal isoforms, to the pathophysiology of congestive heart failure in human beings, we compared expression, localisation, and specific activity of NOS isoforms in myocardium from patients with dilated cardiomyopathy with those in controls who had died from head trauma or intracranial bleeds. ⋯ Our results provide evidence of increased nNOS-derived NO in the failing human heart. Such altered regulation may be important in the pathophysiology of cardiac dysfunction in human congestive heart failure.
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Institutional and health-care system approaches complement bedside strategies to improve care of the critically ill. Focusing on the USA and the UK, we discuss seven approaches: education (especially of non-clinical managers, policy-makers, and the public), organisational guidelines, performance reporting, financial and sociobehavioural incentives to health-care professionals and institutions, regulation, legal requirements, and health-care system reorganisation. No single action is likely to have sustained effect and we recommend a combination of approaches. ⋯ We also recommend more public education and use of organisational guidelines, such as admission criteria and staffing levels in intensive care units. Even if these endeavours are successful, with rising demand for services and continuing pressure to control costs, optimum care of the critically ill will not be realised without a fundamental reorganisation of services. In both the USA and UK, we recommend exploration of regionalised care, akin to US state trauma systems, and greater use of physician-extenders, such as nurse practitioners, to provide enhanced access to specialist care for critical illness.