Structural relationships in the inhibition of [3H]tryptamine binding to rat brain membranes in vitro by phenylalkylamines

The ability of various phenylalkylamines to inhibit the binding of [3H]tryptamine to rat frontal/parietal cortical membranes was examined in vitro. Affinity for [3H]tryptamine binding sites improved as the alkyl side chain was extended to include four carbons or when a methoxy group was added at the para position of the ring. One compound, p-methoxyphenylpropylamine (IC50 = 3.6 nM), was as potent as unlabelled tryptamine as a displacing agent. Based on the unique structure-activity relationship obtained, it appears that [3H]tryptamine binding sites do not mediate the actions of phenethylamines on serotonin uptake or release.     

Fulminant Adenoviral-Induced Hepatitis in Immunosuppressed Patients

Human adenovirus (HAdV) can often lead to fulminant hepatitis in immunocompromised patients, mostly after reactivation of HAdV. Different risk factors, e.g., transplantation and chemotherapy, increase the risk of developing a HAdV hepatitis. We retrospectively analyzed three patients who showed the characteristics of a HAdV hepatitis observed in disseminated disease. In addition to PCR, diagnosis could be proven by pathology, CT scan, and markedly elevated transaminases. All patients had a hemato-oncologic underlying disease. Two had received a stem-cell transplant, and one was under chemotherapy including rituximab. Despite therapy with cidofovir, all patients died. As the incidence of HAdV hepatitis is low, diagnosis may be easily overlooked. No treatment approaches have yet been established. HAdV hepatitis should be considered as a differential diagnosis, especially when risk factors are present. To avoid dissemination, treatment should be initiated as soon as possible.     

Hirschsprung-associated enterocolitis develops independently of NOD2 variants

Backgroud/Purpose

Hirschsprung-associated enterocolitis (HAEC) represents a cause for significant pre- and postoperative morbidity and mortality in Hirschsprung disease (HD). Although multiple studies on HAEC have been performed and several mechanisms have been presumed, the pathogenesis of this condition remains unclear. As changes in colonic mucosal defense are key factors suggested in both Crohn's disease (CD) and HAEC pathogenesis, the aim of the current study was to investigate genetic alterations in the most important susceptibility gene for Crohn's enterocolitis (NOD2) to see whether carriers of polymorphisms within the NOD2 gene are predisposed to the development of HAEC.

Methods

Genotyping for the NOD2 variants in exon 4 (p.Arg702Trp [rs2066844]), exon 8 (p.Gly908Arg [rs2066845]), and exon 11 (p.1007fs [rs2066847]) was performed in 52 white children with HD (41 boys, 11 girls), 152 healthy controls, and 152 children with CD (onset of disease <17 years; mean, 11.8 years). Seventeen patients with HD (32.7%) were carriers of a RET germline mutation, 35 children (67.3%) had short segment disease, and 17 (32.7%) had long segment disease.

Results

Ten children (19.2%) with HD were heterozygous carriers of at least one NOD2 variant vs 17 (11.2%) in the healthy control group and 69 (45.4%) in the CD cohort. Hirschsprung-associated enterocolitis was observed in 7 children (13.5%), with 4 having short segment HD and 3 with long segment HD; but none of them were carriers of NOD2 variants.

Conclusion

Our study shows that NOD2 variants described to be causatively associated with CD do not predispose to the development of HAEC. As data on the molecular basis of HAEC are limited, the distinct mechanisms involved in the pathogenesis of this complication remain unclear.     

Reappraisal of the Traditional Wenckebach Phenomenon with a Modified Ladder Diagram

Understanding of the traditional Wenckebach phenomenon is enhanced by using a modified ladder diagram where AV conduction in any cycle is represented by a slanted line in the AV bar together with similar AV conduction lines of all the preceding cycles. The diagram facilitates calculation of the duration of RR intervals (equal to the basic PP or sinus interval minus the PR or AV increment applied to this particular cycle) and the duration of the pause (equal to 2 × PP or sinus interval minus the sum of all the increments applied to the AV delay). The modified Wenckebach diagram should help students understand the mysterious clustering of QRS complexes or “paradoxical” increase of the ventricular rate that occurs during a Wenckebach sequence. Ann Noninvasive Electrocardiol 2012;17(1):3–7