Wiener klinische Wochenschrift
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Wien. Klin. Wochenschr. · Apr 2004
Review Comparative Study[Future targets in the treatment of type 2 diabetes].
Prevention and treatment of type 2 diabetes mellitus (T2DM) and the metabolic syndrome represent a major clinical challenge, because effective strategies such as fat restriction and exercise are difficult to implement into diabetes treatment. Based on the increasing knowledge on the pathogenesis of T2DM, new therapeutic approaches are currently under investigation. Potential targets of new therapeutic approaches include: (i) Inhibition of hepatic glucose production, (ii) stimulation of glucose-dependent insulin secretion, (iii) enhancement of insulin signal transduction, and (iv) reduction of body fat mass. ⋯ The glucose-lowering effect of current modulators of lipid oxidation is not pronounced and their use could be limited by side effects. In addition to clinically approved thiazolidendiones, new agonists of the peroxisome proliferator activator receptor gamma (PPAR gamma) as well as combined PPAR alpha/gamma agonists are developed at present. The direct modulation of insulin signal transduction is still limited to experimental studies.
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Adequate volume replacement therapy is a mainstay of managing the critically ill. The ideal kind of volume replacement in this situation still remains a challenge. In spite of an immense number of contributions to this problem there is still no definite answer. ⋯ The different physico-chemical properties of the available HES solutions, however, should be taken into account. Anphylactoid reactions as well as negative effects on coagulation, kidney/liver function and on the immune system are frequently used arguments against the administration of HES, but they can virtually be neglected when using modern HES preparations to correct hypovolemia. There are, however, still open questions concerning the use of HES in children, pregnant patients, patients with altered kidney function and in burn patients.
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Acute liver failure is a rare and life-threatening clinical syndrome following severe hepatic injury. Depending on the rapidity of its development, two distinct complications contribute to a high mortality: in hyperacute liver failure, rapid development of massive hepatic necrosis and apoptosis gives rise to severe hyperammonemia, hepatic encephalopathy and life-threatening cerebral edema. The high risk of cerebral herniation requires early listing for emergency liver transplantation. ⋯ Experimental treatment methods including detoxification by artificial or bioartificial liver support or by stimulating hepatic regeneration are currently evaluated. Recognition of ammonia toxicity has stimulated the search for early ammonia-lowering strategies and strongly renewed the interest in dialytic therapies. Anti-apoptotic interventions are among the most promising pharmacological options for the near future.
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Levosimendan (LS) is a new calcium sensitizer that exerts positive inotropic effects without increasing intracellular cAMP or Ca2+ at therapeutic doses and therefore may avoid major limitations of beta-adrenergic agents. LS also causes arteriolar and venous dilation by opening potassium channels on vascular smooth muscle cells. In addition, LS does not increase myocardial oxygen demand and may exert anti-stunning effects. ⋯ LS has a favourable side effect profile and is approved for 24-hour use in congestive heart failure. It may cause hypotension due to vasodilation, and this effect may be aggravated by inadequate preload conditions. Further morbidity and mortality studies are required to confirm the encouraging data from the LIDO and RUSSLAN trial but already the existing data support LS as the inotropic agent of choice in patients with worsening heart failure and a systolic arterial blood pressure beyond 90 mmHg.
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Wheezing in infants and toddlers is a common symptom, and these patients are difficult to approach--both diagnostically and therapeutically. Congenital conditions causing wheezing disorders should not be missed and--not all wheezy bronchitis is or will become asthma. Results from longitudinal studies indicate that the term "asthma" includes different phenotypes: so-called transient early wheezing, non atopic wheezing and atopic wheezing (asthma). ⋯ Only asthma seems to be a progressive disease; and there is evidence from long-term studies that if anti-inflammatory interventions are started late, it might be too late to alter the natural course of the disease with its decline in pulmonary function. On the other hand, there is no evidence that small children with non-atopic wheezy bronchitis would benefit from long-term therapy with anti-inflammatory treatment; in this group a therapeutic trial with bronchodilators is sufficient. The diagnostic and therapeutic challenges of diagnosing asthma in this age group are considerable and require a comprehensive approach.