QT dispersion (QTD) on 12-lead ECGs has been proposed as a marker of malignant ventricular tachyarrhythmias, and increased QTD has been reported in long QT syndrome (LQTS). On the other hand, it has been demonstrated that transmural dispersion is associated with ventricular tachyarrhythmias in an experimental model. However, the precise type of QTD or transmural dispersion that contributes most to ventricular tachyarrhythmias in patients with LQTS remains unclear. We evaluated 27 patients with acquired LQTS. These patients were divided into two groups: group A (n =12), patients with polymorphic ventricular tachycardia [torsades de pointes (TdP)], and group B (n =15), patients without TdP. The QT intervals were corrected using Bazett's formula. QTD was measured as the difference between the maximum and the minimum QT intervals, and T wave peak-to-end interval divided by the QT interval (Tpe) in the V5 lead was measured as a new index. Both the corrected QTD (QTDc) and Tpe were significantly larger in group A than in group B. Logistic regression analysis revealed that a reliable predictor for TdP in the QT variables in these patients was not QTDc but Tpe. Cumulative frequency distributions revealed that a Tpe of 0.28 is a good cut-off point for TdP. Tpe did not correlate with the corrected maximum QT interval, whereas the QTDc did correlate with this parameter. In conclusion, Tpe may be the best predictor for TdP in patients with acquired LQTS.

SummaryBackground: Patients with hypertrophic cardiomyopathy (HCM) associated with a deletion of lysine 183 (K183del) in the cardiac troponin I (cTnI) gene suffer sudden cardiac death at all ages. However, the correlation between QT variables and sudden cardiac death in these patients remains uncertain.Hypothesis: We evaluated the correlation between QT variables and sudden cardiac death and/or ventricular tachyarrhythmia (SCD/VT) in patients with HCM associated with the cTnI mutation.Methods: We analyzed 10 probands with HCM associated with the cTnI gene K183del and their family members. The subjects were divided into three groups: Group A (n = 7), mutation carriers with SCD/VT; Group B (n = 16), mutation carriers without SCD/VT; Group C (n = 24), no mutation carriers. QT intervals were corrected using Bazett's formula.Results: Maximum QTc and corrected QT dispersion were significantly longer in Groups A and B than in Group C. However, there were no differences in either parameter be-

Although many effects of leptin are mediated through the central nervous system, leptin can regulate metabolism through a direct action on peripheral tissues, such as fat and liver. We show here that leptin, at physiological concentrations, acts through an intracellular signaling pathway similar to that activated by insulin in isolated primary rat hepatocytes. This pathway involves stimulation of phosphatidylinositol 3-kinase (PI3K) binding to insulin receptor substrate-1 and insulin receptor substrate-2, activation of PI3K and protein kinase B (AKT), and PI3K-dependent activation of cyclic nucleotide phosphodiesterase 3B, a cAMP-degrading enzyme. One important function of this signaling pathway is to reduce levels of cAMP, because leptin-mediated activation of both protein kinase B and phosphodiesterase 3B is most marked following elevation of cAMP by glucagon, and because leptin suppresses glucagon-induced cAMP elevation in a PI3K-dependent manner. There is little or no expression of the long form leptin receptor in primary rat hepatocytes, and these signaling events are probably mediated through the short forms of the leptin receptor. Thus, leptin, like insulin, induces an intracellular signaling pathway in hepatocytes that culminates in cAMP degradation and an antagonism of the actions of glucagon. Leptin (OB)1 is a 16-kDa protein secreted primarily from adipocytes (1-3). Rodents that are defective in leptin synthesis, the ob/ob mice, or leptin receptor function, the db/db mice, Zucker fa/fa rats, and Koletsky rats, are obese and develop hyperinsulinemia and insulin resistance similar to the metabolic abnormalities associated with type 2 diabetes. Leptin suppresses food intake (4 -7) and increases thermogenesis (8) and metabolic rate (9). These responses appear to be mediated mainly through the central nervous system, because they can be achieved by intracerebroventricular injections of leptin (10, 11). Leptin has also been shown to have a wide repertoire of peripheral effects, some of which are mediated through the central nervous system, and others that are induced through a direct action on target tissues. The latter include direct inhibition of insulin secretion and gene expression in pancreatic ␤-cells, stimulation of fatty acid oxidation in adipocytes, and stimulation of angiogenesis and T-cell proliferation (12-16).Molecular cloning of the leptin receptors (OB-R) has revealed that they are single membrane-spanning receptors with homology to members of the cytokine receptor superfamily (10, 17). The different leptin receptors arise from alternative splicing, and although the extracellular domains of these splice variants are identical, differences are apparent in the intracellular signaling domain. The splice variants containing transmembrane domains can be divided into two groups: one group that has short 32-97 amino acid residue intracellular domains (OB-Ra, -Rc, -Rd, -Rf, and a unique form expressed in hematopoietic cells, termed Rg here) and another group (OB-Rb) that has a long 302-residue intrace...

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Aims: To investigate collagen remodelling in the interstitium of the heart in patients with diabetes. Methods: Immunohistochemical study of the biopsied myocardium using type specific anticollagen antibodies (I, III, IV, V, VI) was performed in 12 patients with non-insulin dependent diabetes mellitus and six non-diabetic patients. There was no history of hypertension or coronary artery stenosis in any of the patients. Results: Noticeable accumulations of collagen types I, III, andVI in the myocardial interstitium were recognised in both groups, but little accumulation of types IV or V was found. Types I and III mainly stained in the perimysium and perivascular region, while type VI predominantly stained in the endomysium. There was no disease specific accumulation of collagen in diabetes mellitus. The percentage of total interstitial fibrosis in the myocardium was significantly higher in the diabetic group than in the control group (p < 0.05). Although the percentages of coliagen types I and VI did not differ between the two groups, the percentage type of III was significantly higher in the diabetic group than in the controls (p < 0-01). Conclusions: Collagen remodelling mainly as a result of an increase in collagen type III in the perimysium and perivascular region, occurs in the hearts of patients with diabetes.