The Krüppel-associated box (KRAB)-zinc finger protein Kid-1 and the Wilms' tumor protein WT1, two transcriptional repressor proteins, bind to heteroduplex DNA.

Zinc finger proteins of the Cys2His2 class represent a large group of DNA-binding proteins. A major subfamily of those proteins, the Krüppel-associated box (KRAB) domain-containing Cys2His2-zinc finger proteins, have been described as potent transcriptional repressors. So far, however, no DNA-binding sites for KRAB domain-containing zinc finger proteins have been isolated. Using a polymerase chain reaction-based selection strategy with double- and single-stranded DNA, we failed to reveal a binding site for Kid-1, one member of KRAB-zinc finger proteins. Binding of Kid-1 both to single- and homoduplex double-stranded DNA was negligible. We now present evidence that Kid-1 binds to heteroduplex DNA. Similar to Kid-1, the non-KRAB-zinc finger protein WT1 also bound avidly to heteroduplex DNA (both the -KTS and +KTS splice variant of WT1), whereas the POU domain protein Oct-6, the ets domain protein Ets-1 and the RING finger of BRCA-1 did not bind to heteroduplex DNA. Binding of WT1 to heteroduplex DNA was markedly reduced in naturally occurring mutants. The recognition of certain DNA structures by transcriptional repressor proteins may therefore represent a more common phenomenon than previously thought.

Risk of right bundle-branch block and complete heart block during pulmonary artery catheterization.

The need for the prophylactic insertion of a pacemaker before pulmonary artery catheterization in patients with pre-existing left bundle-branch block (LBBB) is controversial. To determine the incidence of new right bundle-branch block (RBBB) and complete heart block during bedside pulmonary artery catheterization, 293 patients undergoing 307 pulmonary artery catheterizations were prospectively studied. Nine patients had pacemaker rhythms and 19 patients had an RBBB on their precatheterization ECGs and therefore were excluded from analysis. In the remaining 279 pulmonary artery catheterizations, eight (3%) were associated with the development of a new RBBB. None of the 14 patients with a pre-existing LBBB developed complete heart block. The incidence of complete heart block during pulmonary artery catheterization of patients with previous LBBB was not higher than the incidence of RBBB in patients without underlying conduction defects. Because of the rare but grave consequences of RBBB in patients with pre-existing LBBB, we recommend the use of standby external pacemakers and equipment for transvenous pacemaker insertion in these patients during pulmonary artery catheterization. We do not recommend prophylactic pacemaker insertion.

The adult respiratory distress syndrome.

The adult respiratory distress syndrome (ARDS) is an extreme form of noncardiogenic pulmonary edema associated with alveolar-capillary damage. Clinical features include acute respiratory distress, dyspnea and tachypnea, severe hypoxemia refractory to oxygen therapy, and diffuse bilateral pulmonary infiltrates. Any number of serious disorders can cause ARDS, but the processes leading to the alveolar permeability defect are not understood. Therefore, therapy remains nonspecific and supportive. Treatment includes positive end-expiratory pressure, careful fluid management, steroid therapy, and adequate nutrition. Unfortunately, even with the most sophisticated intensive care, the mortality of ARDS is still greater than 50%.

Intravenous verapamil for termination of re-entrant supraventricular tachycardias: intracardiac studies correlated with plasma verapamil concentrations.

We evaluated efficacy and mechanisms of the antiarrhythmic action of verapamil in 20 patients with sustained supraventricular tachycardia. Two patients had sinus nodal re-entrant tachycardia, nine atrioventricular (AV) nodal re-entrant tachycardia, and nine AV reciprocating tachycardia associated with the Wolff-Parkinson-White syndrome. The study design comprised a double-blind, randomized, cross-over phase using a 0.075 mg/kg dose of verapamil versus placebo and an open-label phase using a 0.15 mg/kg dose of verapamil. The overall results of both phases showed that 15 of 19 patients converted to sinus rhythm with verapamil while only one of 16 converted to sinus rhythm with placebo. The effective plasma verapamil concentration measured 123 +/- 40 ng/mL (mean +/- SD). Verapamil suppressed sinus nodal and AV nodal re-entry but exerted no selective depression between fast and slow AV nodal pathways. It had no significant effect on accessory AV bypass tract but was effective in terminating AV reciprocating tachycardia by its depressive action on the AV node.