Experience with direct acting anti-viral agents for treating hepatitis C virus infection in renal transplant recipients

In recent past, direct-acting anti-viral drugs (DAAs) have become the standard of care for the treatment of hepatitis C virus (HCV) infection. However, the experience with the use of these drugs in Indian renal transplant recipients is limited. We retrospectively reviewed our experience with DAA-based treatment for HCV infection in such patients. Between April 2015 and December 2016, six adults (median age 41 [range 34–52] years, male 5; GT1 2, GT3 3, and GT4 1; including three with prior failed interferon-based treatment) had received genotype-guided, DAA-based anti-HCV treatment 1 to 158 (median 15) months after renal transplantation. Of them, four completed the planned 24-week treatment without any significant adverse event. One of them had increase in serum creatinine after 16 weeks of treatment with sofosbuvir and daclatasvir, with acute interstitial nephritis on kidney biopsy; his renal function improved on stopping the drugs. The other patient had preexisting mild renal dysfunction, which worsened after 8 weeks of sofosbuvir-ledipasvir treatment; this did not reverse on stopping treatment. All the six patients achieved undetectable HCV RNA after 4 weeks of treatment and also achieved sustained virologic response, i.e. lack of detectable HCV RNA in serum 12 weeks after stopping treatment. Overall, DAA-based treatment was effective in treating HCV infection in our renal transplant recipients; however, caution and monitoring of renal function during such treatment is advisable in patients who have additional factors that predispose to renal injury.     

Double Giant Lambl’s Excrescence of aortic valve causing posterior circulation stroke

Diagnostic evaluation of embolic neurologic events requires the consideration of cardiac causes. Lambl’s Excrescences (LE)are filiform fronds that occur at sites of valvular closure due to “wear and tear” (Lambl Wien Med Wschr 6:244–247, 1856). The complex form of LE is “giant Lambl’s Excrescences” which results from the adherence of multiple adjacent excrescences that grow large. We recently had young male adult who presented with features of posterior circulation stroke (basilar) and detected to have two separate giant Lambl’s Excrescences on the aortic valve and treated successfully.     

Evaluation of beta defensin 2 production by chicken heterophils using direct MALDI mass spectrometry

Beta defensins (BD) are cysteine rich, cationic antimicrobial peptides (AMP) produced mainly by epithelial and myeloid cells such as neutrophils. In birds, the neutrophil equivalent heterophils produce avian beta defensins (AvBD) of which AvBD2 is the major isoform. Heterophils recognize pathogens or their derived products through a series of pattern recognition receptors called toll-like receptors (TLR) leading to their antimicrobial activities. This work is the first report of TLR modulation of AvBD2 expression in chickens. To measure the effect of TLR activation on AvBD2 production, the heterophils were cultured with different TLR agonists for 6 h. Modulation of AvBD2 levels by TLR activation was measured using direct MALDI mass spectrometry without stable isotopic labeling or chromatographic separation. Chemical modification of the conditioned media was performed using reduction/alkylation with dithiothreitol/iodoacetamide to distinguish TLR treated AvBD2 (reduced/alkylated) from controls (non-reduced). Changes in corrected ion intensity ratios were assumed to reflect AvBD2 modulation in heterophils upon activation with different TLR agonists. In general, TLR agonists increased AvBD2 production with LPS showing the greatest induction and CpG-ODN showing little or no effect. These data show that the direct MALDI-MS coupled with reduction/alkylation may provide a rapid relative quantitative approach to the measurement of agonist-induced differential expression of AvBD2.     

Effects of procainamide on strength-interval relations in normal and chronically infarcted canine myocardium

The effects of procainamide on strength-interval relations in normal and chronically infarcted canine myocardium were determined in nine adult mongrel dogs susceptible to sustained ventricular tachyarrhythmias. The dogs were studied at 3 to 30 days after two stage occlusion and reperfusion of the mid left anterior descending coronary artery. Unipolar cathodal stimulation (pulse duration 2 ms, drive cycle length 300 ms) was used to evaluate excitability and refractoriness at a total of 19 normal and 22 infarct sites both before and 15 to 30 minutes after intravenous infusion of procainamide, 20 to 25 mg/kg body weight. The electrophysiologic effects of procainamide were evaluated at the time of the plateau phase of procainamide's antiarrhythmic activity in this model. At normal sites, procainamide had only a minimal effect on the mean diastolic excitability threshold (increased from a mean [± standard deviation]of 0.07 ± 0.02 to 0.08 ± 0.02 mA [probability (p) = not significant (NS)], the mean effective refractory period (increased from 137 ± 10 to 139 ± 11 ms [p = NS]) and the mean ventricular refractory period at twice diastolic threshold (increased from 156 ± 12 to 163 ± 16 ms [p <0.01]). At infarct sites, the mean diastolic excitability threshold was similarly unchanged after procainamide (from 0.57 ± 1.13 to 0.57 ± 1.09 mA [p = NS]), but both the mean effective refractory period (from 142 ± 17 to 159 ± 27 ms [p <0.001]) and the mean ventricular refractory period at twice diastolic threshold (from 166 ± 25 to 187 ± 33 ms [p <0.001]) were moderately prolonged. In addition, dispersion of refractoriness between normal and infarct sites as well as within areas of infarcted myocardium was often either unchanged or increased rather than decreased by procainamide.

Thus, the antiarrhythmic activity of procainamide in this canine model of chronic myocardial infarction was not explained by an effect on the excitability or refractoriness of normal myocardium, by changes in the diastolic excitability of infarcted tissue or by an effect on the dispersion of refractoriness. The most prominent effect of procainamide was to decrease the excitability of abnormal myocardium during the relative refractory period and to prolong the refractoriness of abnormal myocardium.