Congenital mesoblastic nephroma and trisomy 11.

Cytogenetic analysis of a congenital mesoblastic nephroma (CMN) in a 1-month-old boy showed a 48,XY, +10, +11 karyotype. In this particular tumor type, chromosomal changes are found in almost all cases. Among the numerical changes, trisomy 11 stands out, whereas involvement of the long arm of chromosome 15 may be a nonrandomly occurring structural change.

Distribution of varicella zoster virus and herpes simplex virus in disseminated fatal infections.

AIMS: To study the cutaneous and visceral distribution of herpes simplex virus (HSV) and varicella zoster virus (VZV) in fatal infections. METHODS: Standard histology, immunohistochemistry (monoclonal antibodies VL8 and VL2 and polyclonal antibody IE63 directed against VZV; monoclonal antibodies IBD4 and HH2 and polyclonal antibodies directed against HSVI and HSVII) and in situ hybridisation (anti-HSV and anti-VZV probes) were applied to formalin fixed, paraffin wax sections. RESULTS: On histological examination, Herpesviridae infection was evident in various organs including the lungs, liver and skin. In addition, immunohistochemistry and in situ hybridisation revealed the presence of HSV and VZV antigens and nucleic acids in several cell types and tissues showing no cytopathological alterations suggestive of Herpesviridae infection. The organs with histological evidence of infection also contained VZV or HSV antigens and their genes. CONCLUSIONS: These findings suggest that organ failure in disseminated VZV and HSV infections is primarily caused by HSV or VZV induced cell damage and lysis. They also indicate that immunohistochemistry and in situ hybridisation can provide an accurate, type-specific diagnosis on formalin fixed, paraffin wax embedded tissue even when classic histological and cytological characteristics are lacking.

Reproducible induction of early afterdepolarizations and torsade de pointes arrhythmias by d-sotalol and pacing in dogs with chronic atrioventricular block.

It has been well established that antiarrhythmic drugs can also have proarrhythmic effects such as torsade de pointes (TdP) arrhythmias. It was the purpose of this study to create an animal model with a high incidence of reproducible TdP that occurs under clinically relevant circumstances. Experiments were performed in anesthetized dogs that had been in chronic atrioventricular block for 9 +/- 6 weeks. TdP inducibility was attempted using different pacing modes before and after the administration of 2 mg/kg d-sotalol. In some experiments, endocardial monophasic action potentials were recorded. d-Sotalol increased the cycle length of the idioventricular rhythm (1475 +/- 460 to 1730 +/- 570 ms, P < .01) and the QT time (390 +/- 65 to 480 +/- 85 ms, P < .01). In 10% of the experiments, spontaneous TdP occurred after d-sotalol. The incidence of pacing-dependent TdP was 52% (P < .01). In the inducible group, the cycle length of idioventricular rhythm and QT time were significantly longer despite equal percentage increases in these parameters after d-sotalol in both groups. The pacing modes consisting of more than one frequency change had a higher TdP induction rate (P < .05). Reproducibility of TdP induction (three times or more using the same pacing train) remained present for approximately 60 minutes after d-sotalol and was greater than 90% within the same animal over weeks. TdP induction was related to the presence of early afterdepolarizations on the monophasic action potential recordings: five of six in the inducible group versus two of six in the nonresponders. Inducibility could be further increased to 89% when a second bolus of d-sotalol was administered to noninducible dogs. On the other hand, decreasing QT time by faster basic pacing or administration of isoproterenol, or MgSO4 prevented TdP induction. This effect of MgSO4 coincided with the disappearance of early afterdepolarizations. Our animal model shows a high incidence of reproducible acquired TdP arrhythmias, allowing study of the mechanism and treatment of TdP. TdP induction was related to the combination of a slow ventricular rate, the prolongation of QT time, a sudden induced rate change that often required two or more cycle length changes, and the presence of early afterdepolarizations.

Mechanism-specific antiarrhythmic effects of the potassium channel activator levcromakalim against repolarization-dependent tachycardias.

INTRODUCTION: The hypothesis that levcromakalim, a potassium channel (IK-ATP) activator with antihypertensive properties, has a mechanism-specific antiarrhythmic action against repolarization-dependent ventricular tachycardias (VTs) was tested in dogs. METHODS AND RESULTS: A low dose of levcromakalim (0.01 mg/kg) was selected, which decreased blood pressure by 25% but had almost no electrophysiologic effect on AV nodal or ventricular conduction or effective refractory period. In dogs with chronic AV block, the antiarrhythmic action of this dose of levcromakalim was evaluated in three models of abnormal impulse formation: (1) d-sotalol (2 mg/kg) induced torsades de pointes VT, initiated by early afterdepolarizations (EADs), (2) sustained ouabain-induced VTs, which are dependent on delayed afterdepolarizations (DADs), and (3) VT occurring 24 hours after left anterior descending coronary artery occlusion, which are likely based on abnormal automaticity. Levcromakalim abolished d-sotalol induced U waves, ventricular ectopic beats, and self-terminating bouts of torsades de pointes. Induction of torsades de pointes by pacing was also completely prevented. The cycle length of the idioventricular rhythm, which was lengthened after d-sotalol from 1490 +/- 515 to 1700 +/- 610 msec (P < 0.05), remained similar after levcromakalim (1655 +/- 580 msec). The QT(U) duration, which was increased after d-sotalol from 410 +/- 55 to 550 +/- 40 msec (P < 0.05), normalized to 405 +/- 70 msec (P < 0.05). Levcromakalim did not suppress but rather enhanced ouabain-induced VT by decreasing the cycle length slightly from 315 +/- 35 to 290 +/- 35 msec (P < 0.05). Pretreatment with a beta blocker prevented this acceleration in rate. Finally, levcromakalim had no effect on VT 24 hours after infarction. CONCLUSION: A low dose of levcromakalim has specific antiarrhythmic properties against repolarization-dependent arrhythmias, but it does not affect VTs based on other mechanisms of abnormal impulse formation.

Identification of patients at high risk for recurrence of sustained ventricular tachycardia after healing of acute myocardial infarction.

A prognostic index for nonfatal recurrences of ventricular tachycardia (VT) was developed using a retrospective analysis of a group of 206 patients with sustained monomorphic VT or ventricular fibrillation (VF) after healing of acute myocardial infarction. 74 patients (36%) (64 with VT and 10 with VF) had recurrences of sustained monomorphic VT during 3.4 +/- 9 years of follow-up. Three clinical variables were selected and weighted by stepwise logistic discriminant analysis of the study group. They were coded as follows: interval of myocardial infarction to arrhythmia (less than 2 months = 1; 2 to 6 months = 2; greater than 6 months = 3), drug therapy with or without sotalol (with = 1, without = 2), and VT or VF as the presenting arrhythmia (VT = 1, VF = 2). The prognostic index was: 3.41 - (0.56 x interval) - (1.94 x therapy) + (0.86 x arrhythmia). This index was validated prospectively in a test group of 158 consecutive patients with VT or VF after healing of acute myocardial infarction. Patients were allocated into different classes with decreasing prognostic index values associated with increasing risk for recurrences of VT. In the test group, 27 of 158 (17%) patients (22 with VT and 5 with VF) had recurrences of VT (follow-up of 2 +/- 2 years). Two risk classes of patients were identified: high risk for recurrences of VT (61%) corresponding to patients with a negative index; and low risk (4%) consisting of those with a positive index. Thus, using O as the cutoff point, the sensitivity, specificity, and positive and negative predictive values were 81, 89, 62 and 96%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)