Annals of medicine
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Concern is often expressed that, in the future, screening for genetic risk will become too widespread. Haemoglobin disorders (the thalassaemias and sickle cell disorders) offer an excellent model for genetic screening, because they are common and severe. They are recessively inherited. ⋯ Carrier-screening programmes have been in place in several countries for over 20 years and now offer extensive practical experience of the problems of delivering the service equitably to entire populations. This experience suggests that the main risk is of too little rather than too much genetic screening, and of doing it badly, and demonstrates the need for a discipline of 'community genetics'. Here I propose that modern information technology has a central role in providing communities with adequate access to correct genetic information.
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Sudden arrhythmic death is the most common mode of death in Western countries. An increased understanding of the pathophysiology and trigger mechanisms of life-threatening ventricular tachyarrhythmias in patients with structural heart disease can provide a logical basis for improved therapeutic strategies in the prevention of sudden death. Analysis of heart rate variability (HRV) from ambulatory electrocadiographic recordings can identify the patients at increased risk for arrhythmic death after an acute myocardial infarction. ⋯ Recently, quantitative analysis of Poincaré plots of successive R-R intervals has shown that reduced long-term R-R interval variability, associated with episodes of beat-to-beat sinus alternans, is a specific sign of a propensity for spontaneous onset of ventricular tachycardia. These studies suggest that abnormal heart rate behaviour reflects an electrical instability favoring the onset of life-threatening arrhythmia and provide evidence that altered neurohumoral or autonomic regulation is an important trigger mechanism for the spontaneous onset of life-threatening arrhythmia. Future research in larger patient populations will reveal whether analysis of dynamic behaviour of cardiac electrical signals will give new insights into the mechanisms of life-threatening arrhythmias and help in the development of new therapeutic options for the prevention of sudden arrhythmic death.
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The term fibromyalgia describes a complex syndrome characterized by pain amplification, musculoskeletal discomfort, and systemic symptoms. Although its existence has been controversial, nearly all rheumatologists now accept fibromyalgia as a distinct diagnostic entity. In fact, in the United States it is the third or fourth most common reason for rheumatology referral. Exciting new insights into the aetiology, pathogenesis, diagnosis and treatment of fibromyalgia will be reviewed.
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Receptors for many of the cytokines functioning in the haematopoietic system belong to the class I cytokine receptor family. In most cases these receptors share common signal transducing receptor components in the same family, which explains the functional redundancy of haematopoietic cytokines. Interleukin-6 and related cytokines, interleukin-11, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and cardiotrophin-1, are all pleiotrophic, from the haematopoietic to the nervous system, and exhibit overlapping biological activities. ⋯ In these receptor complexes, gp130 and ligand-specific chains possess no intrinsic tyrosine kinase domain but are associated with cytoplasmic tyrosine kinases. Ligand stimulation triggers homo- or heterodimerization of gp130, leading to activation of the associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors. This paper reviews the recent progress in the study of gp130 and the background information from biomedical and biochemical viewpoints.
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The recent identification of mutations in the RET proto-oncogene that are associated with multiple endocrine neoplasia type 2 (MEN 2) syndromes has allowed therapeutic intervention in affected individuals on the basis of direct genetic testing. The principal endocrine neoplasm that occurs in patients with the MEN 2 syndromes is medullary thyroid carcinoma. This thyroid neoplasm is the only consistently malignant feature of the MEN 2 syndromes and it is the most common cause of death in affected patients. ⋯ Those with a positive test can be treated by early thyroidectomy and cured when the disease is microscopic and localized to the thyroid gland. Total thyroidectomy is performed as early as 5 years of age and is associated with minimal morbidity and virtually no mortality. Residual or persistent medullary thyroid carcinoma following thyroidectomy can best be determined by detecting increased levels of calcitonin following the administration of intravenous calcium gluconate and pentagastrin.