Inappropriate defibrillator shocks from depolarization--repolarization mismatch in a patient with hypertrophy cardiomyopathy

Despite wide use of dedicated bipolar sensing electrodes in implantable cardioverter-defibrillator (ICD) systems, oversensing occasionally occurs, leading to unwarranted shocks or antitachycardia pacing. This case report highlights an individual with hypertrophic cardiomyopathy (HCM) who experienced inappropriate shocks from oversensing of repolarization electrograms (T-waves). During the implantation procedure, no excessive T-wave amplitudes were detected during sinus rhythm, ventricular pacing, or induced ventricular fibrillation. T-wave oversensing leading to shocks only developed after maturation of the lead-tissue interface. An adequate safety margin for discrimination between ventricular electrograms and T-waves could not be assured. Thus, insertion of a new dedicated pacing-sensing electrode was required. The degree to which intracardiac repolarization signals may be heightened in patients with HCM has not been investigated systematically. However, a relative decrease in the ventricular electrogram amplitude without a concomitant decline of the intracardiac T-wave amplitude appears to have led to the problem in this patient. Special caution in technique and device selection with a particular emphasis on T-wave sensing may be prudent when ICDs are implanted in individuals with HCM. Additional programmable variables may also be beneficial in such cases.     

Fluid balance in pediatric postoperative liver transplant recipients

Background

Positive fluid balance (FB) is associated with poor outcomes in critically ill children but has not been studied in pediatric liver transplant (LT) recipients. Our goal is to investigate the relationship between postoperative FB and outcomes in pediatric LT recipients.

Methods

We performed a retrospective cohort study of first-time pediatric LT recipients at a quaternary care children's hospital. Patients were stratified into three groups based on their FB in the first 72 h postoperatively: <10%, 10–20%, and > 20%. Outcomes were pediatric intensive care unit (PICU) and hospital length of stay, ventilator-free days (VFD) at 28 days, day 3 severe acute kidney injury, and postoperative complications. Multivariate analyses were adjusted for age, preoperative admission status, and Pediatric Risk of Mortality (PRISM)-III score.

Results

We included 129 patients with median PRISM-III score of 9 (interquartile range, IQR 7–15) and calculated Pediatric End-stage Liver Disease score of 15 (IQR 2–23). A total of 37 patients (28.7%) had 10–20% FB, and 26 (20.2%) had >20% FB. Greater than 20% FB was associated with an increased likelihood of an additional PICU day (adjusted incident rate ratio [aIRR] 1.62, 95% CI: 1.18–2.24), an additional hospital day (aIRR 1.39, 95% CI: 1.10–1.77), and lower likelihood of a VFD at 28 days (aIRR 0.85, 95% CI: 0.74–0.97). There were no differences between groups in the likelihood of postoperative complications.

Conclusions

In pediatric LT recipients, >20% FB at 72 h postoperatively is associated with increased morbidities, independent of age and severity of illness. Additional studies are needed to explore the impact of fluid management strategies on outcomes.     

Drugs of abuse as memory modulators: a study of cocaine in rats

Rationale

It has been proposed that drugs of abuse reinforce behavior partly, or wholly, because they facilitate learning by enhancing memory consolidation. Cocaine can clearly serve as a reinforcer, but its effect on learning has not been fully characterized.

Objectives

To explore the effects of different regimens of pre- and post-training cocaine administration on win-stay and object learning.

Methods

Cocaine naïve and cocaine pre-exposed (30 mg/kg/day, ×5 days followed by 7 days drug-free) male Sprague-Dawley rats received cocaine (0, 1, 2.5, 7.5, or 20 mg/kg, i.p.) immediately following training on a win-stay task in a radial maze or following the sample phase of an object learning task. Win-stay performance was also assessed in tests of extinction and after a set shift.

Results

Post-training cocaine did not improve accuracy on the win-stay task and produced performance deficits at 20 mg/kg. These deficits were attenuated by prior cocaine exposure. There was indirect evidence of facilitated learning in extinction and set shift tests, but the effective dosage was different (2.5 and 7.5 mg/kg, respectively). Post-training cocaine produced dose-dependent improvements in object learning.

Conclusion

Post-training cocaine administration can facilitate learning, but this effect is highly dependent on the dose and the type of task employed.     

Etoposide causes illegitimate V(D)J recombination in human lymphoid leukemic cells

Etoposide is one of the most widely used antineoplastics. Unfortunately, the same treatment schedules associated with impressive efficacy are associated with an increased risk of secondary acute myeloid leukemia (AML), which has prompted its withdrawal from some treatment regimens, thereby potentially compromising efficacy against the original tumor. Because etoposide-associated AML is characterized by site-specific illegitimate DNA recombination, we studied whether etoposide could directly cause site-specific deletions of exons 2 and 3 in the hprt gene. Human lymphoid CCRF-CEM cells were treated with etoposide for 4 hours, and DNA was isolated after subculturing. The deletion of exons 2 and 3 from hprt was assayed by a quantitative polymerase chain reaction (PCR) method. In the absence of etoposide treatment, the frequency of deletions of exons 2 and 3 was very low (5.05 x 10(-8)). After exposure to 10 mumol/ L etoposide, the frequency of the exon 2 + 3 deletion was increased immediately after and at 24 hours after etoposide treatment (65 to 89 x 10(-8)) and increased to higher levels (128 to 173 x 10(-8)) after 2 and 6 days of subculture (P < .001 overall). The frequency of the exon 2 + 3 deletion assessed at 6 days of subculture after 4 hours of 0, 0.25, 1, 2.5, 5, and 10 mumol/L etoposide treatment increased with etoposide concentration, ie, 5.05 x 10(-8), 89.2 x 10(-8), 108 x 10(-8), 142 x 10(-8), 163 x 10(-8), and 173 x 10(-8), respectively (P < .0001). Sequencing of a subset of amplified products confirmed the presence of DNA sequences at the breakpoints consistent with V(D)J recombination. By contrast, exon 2 + 3 deletions after etoposide treatment in the myeloid cell lines KG-1A and K562 showed no evidence of V(D)J recombinase in their genesis. We conclude that etoposide can induce the illegitimate site-specific action of V(D)J recombinase on an unnatural DNA substrate after a single treatment in human lymphoid cells.