Clinical experience with a new detection algorithm for differentiation of supraventricular from ventricular tachycardia in a dual-chamber defibrillator

INTRODUCTION: Inadequate therapy for supraventricular tachyarrhythmias (SVT) is a frequent problem of implantable cardioverter defibrillators (ICD). Dual-chamber ICDs have been developed to improve discrimination of SVT from ventricular tachycardia (VT). We investigated the positive predictivity, sensitivity, and specificity of a new algorithm, the SMART detection trade mark algorithm, incorporated in the Phylax AV (Biotronik) dual-chamber ICD. METHODS AND RESULTS: Two hundred nine patients (185 men, age 64 +/- 11 years) received a Phylax AV ICD with SMART detection trade mark activated. In 138 of these patients, 1,245 sustained tachycardia episodes with a detailed electrogram were stored in the device during a follow-up period of 10 +/- 6 months. Episodes were correctly classified as ventricular fibrillation (VF, n = 178) in 52 patients, VT (n = 641) in 98 patients, and SVT (n = 385) in 48 patients by the algorithm. Forty-one true SVT episodes (3.3%) were misclassified as VT: atrial fibrillation (n = 7) and flutter (n = 1), sinus tachycardia (n = 12), and other SVT (n = 21). The positive predictivity for VF/VT was 94.5% (95% CI 92.7-95.8) uncorrected and 94.5% (95% CI 92.9-95.8%) corrected with the generalized equation estimation (GEE) method. The positive predictivity for SVT was 100%. The specificity was 88.9% (95% CI 85.6-91.6%) uncorrected and 89.0% (95% CI 85.6-91.6%) corrected with the GEE method with a sensitivity of 100%. CONCLUSION: The SMART detection trade mark algorithm was safe and reliable for the detection of all ventricular tachycardias. Although its specificity was high, it should be improved with regard to SVT to avoid inappropriate ICD therapies.     

Synergistic action of calcium ionophore A23187 and phorbol ester TPA on B-chronic lymphocytic leukemia cells

The peripheral blood mononuclear cells from 16 patients with B-chronic lymphocytic leukemia (B-CLL, n = 13), B-prolymphocytic leukemia (B-PLL, n = 2) or hairy cell leukemia (n = 1) were incubated in the presence of the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore A23187. A synergy between these inducers was found with respect to morphological changes and B cell proliferation and differentiation. A23187 used alone did not activate the cells. B-CLL cells treated with the double stimulus acquired a plasmacytoid morphology, showed significantly higher incorporation of 3H-thymidine and 3H-uridine, and produced significantly higher amounts of monoclonal immunoglobulin compared with the same cells exposed to either of the inducers alone. These results indicate that phorbol ester and calcium ionophore act synergistically on B-CLL cells to induce proliferation and differentiation. B-PLL cells responded more vigorously to the signals provided by TPA and A23187. Previous studies showed that TPA and A23187 can mimic the two physiological second messengers diacylglycerol and inositol trisphosphate in the transduction of signals leading to cell activation, proliferation, and differentiation in normal B cells. The present findings suggest that the capacity of B- CLL and B-PLL cells to differentiate in response to signals of the second messenger pathway is intact.     

The natural history of factor VIII:C inhibitors in patients with hemophilia A: a national cooperative study. II. Observations on the initial development of factor VIII:C inhibitors

During a 4-year multicenter cooperative study of acquired factor VIII inhibitors in persons with hemophilia A, new inhibitors were detected in 31 of 1,306 patients who entered the study without an inhibitor or the history of an inhibitor. The incidence of new inhibitors was eight per 1,000 patient-years of observation. The factor VIII:C level before inhibitor development was less than or equal to 0.03 U/mL in 29 individuals and 0.06 U/mL and 0.07 U/mL in the remaining two. Factor VIII:Ag levels were measured in 27 individuals and were less than 0.03 U/mL in 23 and 0.05 to 0.11 U/mL in the remaining four. Maximum inhibitor levels ranged from 1.0 to 9,044 Bethesda U/mL. In seven patients under the age of 20, relatively weak inhibitors (none higher than 4.3 Bethesda U/mL) were detected on only a single occasion despite continued factor VIII challenge. In the other 24 patients with inhibitors detected on multiple occasions, 50% had appeared by age 20 and 71% by age 30. Seventeen of the 31 inhibitors, including 12 of 15 with maximum values greater than 10 Bethesda U/mL, developed within 75 exposure days to factor VIII.     

Recombinant vaccinia viruses for the characterization of Plasmodium falciparum-specific cytotoxic T lymphocytes: recognition of processed antigen despite limited re-stimulation efficacy

Cytotoxic T lymphocytes (CTL) have been implicated in immunity to Plasmodium falciparum infection and disease. We have previously described the use of peptides to define malaria-specific CTL epitopes. To determine whether these peptide epitopes are processed intracellularly from the whole antigen we have developed recombinant vaccinia viruses (rVV) expressing three malaria antigens: thrombospondin-related adhesive protein (TRAP), Pfs16 and the C- terminal half of liver-stage antigen (LSA)-1. Target cells infected with recombinant viruses were lysed by malaria-specific CTL from semi- immune African donors. We also tested the ability of cells infected with these recombinant vaccinia viruses to re-stimulate malaria- specific CTL in peripheral blood lymphocytes from malaria immune adults. Two other pox virus recombinants, NYVAC, an attenuated vaccinia virus, and ALVAC, a canarypox virus, both expressing malaria antigens were also evaluated for their ability to stimulate malaria-specific CTL in contrast to peptide, none of these viruses successfully re- stimulated CTL from the peripheral blood lymphocytes of semi-immune donors. The ability of human CTL from naturally exposed individuals to recognize processed antigen supports the relevance of these cells in protective immunity to malaria.      

Percutaneous dilation of benign biliary strictures

Percutaneous balloon dilation of benign biliary strictures was successful in 15 of 18 patients in whom the procedure was attempted. Successful dilation was achieved in nine of 11 patients who had biliary enteric strictures, with follow-up of 22-55 months (mean, 35.4 months) after catheter removal in seven patients. Five of six strictures in the biliary tree that developed after surgery were successfully dilated, with long-term follow-up available in two patients (58 and 42 months). A patient with an inflammatory common bile duct stricture that was successfully dilated was followed up for 18 months. Percutaneous dilation of biliary tract strictures is a promising technique with good long-term results and may be the initial treatment of choice in biliary stricture management.