Annals of medicine
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This paper concentrates on the genetic aspects of pulmonary arterial hypertension (PAH), a diagnostically based subclass of pulmonary hypertension that includes primary pulmonary hypertension (PPH). During the past year, patients with familial and sporadic PPH were found to have germline heterozygous missense, nonsense and frameshift mutations in bone morphogenetic protein receptor II (BMPR2). Mutations in BMPR2, a member of the transforming growth factor-beta (TGF-beta) receptor superfamily, are predicted to interrupt the bone morphogenetic protein (BMP) signalling pathway, resulting in proliferation, rather than apoptosis of cells within small arterioles. ⋯ The failure to find BMPR2 mutations in all families with familial PPH and in all patients with sporadic PPH suggests that other genes remain to be identified. Mutations in ALK1, a TGF-beta type 1 receptor, previously known to cause type 2 hereditary haemorrhagic telangiectasia (HHT), have also been reported in a few HHT families with clinical and histological features of PPH. The clinical development of PPH, as in neoplasia, appears to require 'two hits' The two hits can be provided either by genetic or environmental factors.
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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.