Annals of medicine
-
Meta Analysis
Effects of thyroid hormone suppression therapy on adverse clinical outcomes in thyroid cancer.
Long-term thyroid hormone (TH) therapy aiming at the suppression of serum thyrotropin (TSH) has been traditionally used in the management of well differentiated thyroid cancer (ThyrCa). However, formal validation of the effects of thyroid hormone suppression therapy (THST) through randomized controlled trials is lacking. Additionally, the role - if any - of TSH effect at low ambient concentrations upon human thyroid tumorigenesis remains unclear. ⋯ THST appears justified in ThyrCa patients following initial therapy. As most primary studies were imperfect, future research will better define the effect of THST upon ThyrCa clinical outcomes.
-
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.
-
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.
-
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.
-
Randomized Controlled Trial Clinical Trial
Brain natriuretic peptide-guided therapy for heart failure.
The drug treatment of heart failure, once simple, has become complex. Apart from a loop diuretic and digoxin, most patients should now be receiving an angiotensin-converting enzyme inhibitor (or angiotensin II receptor blocker), a beta-blocker and spironolactone. Newer drugs, such as endothelin-receptor antagonists and combined blockers of converting-enzyme and neutral endopeptidase, might soon become available. ⋯ In a pilot study, 69 patients were randomized to drug treatment based on clinical criteria, or based on plasma levels of N-BNP. After a median follow-up of 9.6 months, those in the N-BNP group had fewer clinical end-points than those in the group managed by clinical criteria alone (19 vs 54; P= 0.02). These preliminary data encourage the concept that the increasingly complex pharmacotherapy for heart failure, both chronic (as in this trial) and acute, might best be guided by an objective measure such as plasma levels of BNP or N-BNP.