Annals of medicine
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Subcutaneous insulin has been used to treat diabetes since the 1920s; however, despite a number of different formulations, intensive insulin therapy with multiple daily injections has not gained widespread clinical acceptance. Attempts to find effective, well-tolerated, nonenteral routes for delivering insulin began in the 1920s, and, over the years, have included ocular, buccal, rectal, vaginal, oral, nasal and uterine delivery systems. Until recently, many researchers believed that insulin delivered noninvasively was associated with too low a bioavailability to offer a realistic clinical approach. ⋯ Critically, inhaled insulin shows a more physiological insulin profile than that seen with conventional insulin. Further studies are needed to confirm long-term efficacy and pulmonary safety, to compare the different approaches, and to characterize better their relative places in practice. As a result of the recognition of the importance of tighter control of glycaemia and the growing number of patients with type 2 diabetes who receive insulin, inhaled insulin could become an increasingly integral part of managing diabetes.
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Exercise intolerance is a common presentation of metabolic myopathies, especially of congenital errors of glycogen and lipid metabolism. Recently, however, exercise intolerance has been associated with specific defects in protein-coding genes of mitochondrial DNA (mtDNA), including mutations in genes for complex I, complex III, and complex IV. Contrary to the general rules of mitochondrial genetics, all patients were sporadic cases and all mutations were restricted to skeletal muscle, suggesting that they were somatic mutations not affecting the germ line.
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Established in 1987, the EuroQol Group initially comprised a network of international, multilingual and multidisciplinary researchers from seven centres in Finland, the Netherlands, Norway, Sweden and the UK. Nowadays, the Group comprises researchers from Canada, Denmark, Germany, Greece, Japan, New Zealand, Slovenia, Spain, the USA and Zimbabwe. The process of shared development and local experimentation resulted in EQ-5D, a generic measure of health status that provides a simple descriptive profile and a single index value that can be used in the clinical and economic evaluation of health care and in population health surveys. ⋯ EQ-5D is also being used by eight out of the first 10 of the top 50 pharmaceutical companies listed in the annual report of Pharma Business (November/December 1999). Furthermore, EQ-5D is one of the handful of measures recommended for use in cost-effectiveness analyses by the Washington Panel on Cost Effectiveness in Health and Medicine. EQ-5D has now been translated into most major languages with the EuroQol Group closely monitoring the process.
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In the United States, between 40 and 90 million hospital days are lost per year as a result of trauma and surgical procedures which result in the loss of functional tissue. This is estimated to cost the economy and healthcare providers in excess of US$ 500 billion, a figure that is increasing because of extending population lifespan. ⋯ Over the last decade, numerous proteins have been identified that are able to direct the synthesis of new tissue. Such proteins include growth factors, cytokines and, more recently, transcription factors.
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Lithium is a potent prophylactic medication and mood stabilizer in bipolar disorder. However, clinical outcome is variable, and its therapeutic effect manifests after a period of chronic treatment, implying a progressive and complex biological response process. Signal transduction systems known to be perturbed by lithium involve phosphoinositide (PI) turnover, activation of the Wnt pathway via inhibition of glycogen synthase kinase-3beta (GSK-3beta), and a growth factor-induced, Akt-mediated signalling that promotes cell survival. ⋯ Lithium-perturbed genes, particularly those that map to susceptibility regions, could be candidate risk-conferring factors for mood disorders. Transcript and protein profiling in patients could reveal a lithium fingerprint for responsiveness or nonresponsiveness, and a signature motif that may be diagnostic of a specific phenotype. Similarly, lithium-sensitive gene products could provide a new generation of pharmacological targets.