Time Dependent Changes in Duration of Ventricular Repolarization After AV Node Ablation: Insights into the Possible Mechanism of Postprocedural Sudden Death

DIZON, J., et al. : Time Dependent Changes in Duration of Ventricular Repolarization After AV Node Ablation: Insights into the Possible Mechanism of Postprocedural Sudden Death. Although effective, there is a disturbing incidence of sudden death after AV node ablation. The mechanism may be related to proarrhythmia associated with prolongation in ventricular repolarization from the sudden decrease in heart rate. To examine this issue, we studied 15 patients undergoing complete radiofrequency ablation of the AV node for rapid atrial arrhythmias. Twelve‐lead ECGs of paced rhythms at rates of 60, 80, 100, and 120 beats/min were recorded at time points of 30 minutes, 24 hours, 1 week, and 1 month after ablation. The QT interval was measured in the limb and precordial leads with the best T wave offset. The change in the QT interval (ΔQT) relative to the measurement at 30‐minute postablation was calculated. For comparison, a similar procedure was performed on patients receiving pacemakers for primary bradycardia (n = 5 ). The mean QT interval at 60 beats/min, 30‐minutes postablation was significantly longer than at time points thereafter (482 ± 39 vs 446 ± 28 ms at 1 month, limb leads, for example, P < 0.05 ). Analysis of ΔQT revealed a significant shortening of the QT interval at nearly every paced rate at every time point relative to the value at 30‐minute postablation. The QT intervals shortened and stabilized after 24 hours. Neither the QT interval nor ΔQT changed significantly in patients paced for primary bradycardia. We conclude that there is a relative increase in the duration of ventricular repolarization after AV node ablation, which then decreases and stabilizes after 24 hours. Such changes are not seen in patients being paced for primary bradycardia. This data is consistent with the hypothesis that sudden death after AV node ablation may be related to proarrhythmia from prolonged ventricular repolarization.     

Review article: Luminex technology for HLA antibody detection in organ transplantation

Since its inception in the early 1960s, the serologically based complement-dependent cytotoxicity (CDC) assay has been the cornerstone technique for the detection of human leucocyte antigen (HLA) antibodies, not only in pre-transplant renal patients, but also in other forms of organ transplantation. Recently, solid phase assays have been developed and introduced for this purpose, and in particular the Flow-based bead assays such as the Luminex system. This latter assay has proved to be far more sensitive than the CDC assay and has revealed pre-sensitization in potential transplant recipients not detected by other methods of HLA antibody detection. However, the clinical implications of this increased sensitivity have not been convincingly demonstrated until recently. This technology for HLA antibody detection permits the evaluation of the clinical importance of antibodies directed at, for example, HLA-DPB1 and HLA-DQA1, which has not been possible to date. There are Luminex issues, however, requiring resolution such as the ability to distinguish between complement fixing and non-complement fixing antibodies and determination of their relative clinical significance. Luminex technology will permit a re-evaluation of the role of HLA antibodies in both early and late antibody-mediated rejection.     

A FEASIBILITY STUDY OF GENE GUN MEDIATED IMMUNOTHERAPY FOR RENAL CELL CARCINOMA

PURPOSE: Gene modified autologous tumor cell vaccines have demonstrated a protective and therapeutic effect in murine tumor model systems. The majority of trials to date have used viral methods of gene transfer for vaccine construction. An alternative approach to transfer genes into tumor cells is to use the gene gun, which is a physical method of gene transfection that produces high levels of gene expression without viral agents. We establish the feasibility of generating cytokine secreting autologous renal tumor cell vaccines for use in gene therapy for metastatic renal cell carcinoma. MATERIALS AND METHODS: We obtained 1 cm3 tumor tissue from 12 patients undergoing resection of primary or metastatic renal cell carcinoma. The tumor was disaggregated and placed in culture. The phenotype of the primary renal cell lines was established by microscopy and immunohistochemistry. The 1x10(7) lethally irradiated tumor cells were transfected with plasmid deoxyribonucleic acid containing the human (h) granulocyte-macrophage colony-stimulating factor (GM-CSF) gene under control of a cytomegalovirus promoter using the gene gun. The hGM-CSF production was assayed by enzyme-linked immunosorbent assay in the cell culture media 24 hours after transfection. RESULTS: Of 12 tumor samples 8 grew rapidly to produce a mean of 1.8x10(8) cells after 4 to 5 passages in culture, which was sufficient to produce between 24 and 32 vaccines. Immunocytochemistry confirmed that all cultures were almost exclusively renal tumor cells. Gene gun mediated transfection of lethally irradiated tumor cells resulted in high levels of hGM-CSF production (mean 330 ng./10(6) cells per 24 hours). CONCLUSIONS: We have demonstrated the feasibility of producing cytokine secreting tumor cell vaccines from primary and metastatic human renal tumors, and plan to use this approach in phase I clinical trials of gene therapy for metastatic renal cell carcinoma.     

Intracoronary Radiation Post PTCA Prevents Late Arterial Constriction

Vascular constriction post PTCA is a major component in the mechanism of restenosis following intervention. Ionizing radiation demonstrated reduction of neointima formation after injury in animal models and lowered the restenosis rates in pilot clinical studies. To determine the effect of intracoronary radiation therapy on vascular remodeling, angiograms from two radiation trials were analyzed by QCA methods. Patients in these trials had de novo lesions and were treated with balloon angioplasty followed by either beta or gamma radiation. All patients were studied angiographically at 6 months; patients with total occlusion at the treated artery were excluded from the analysis. In the gamma trial, 192-Iridium was utilized in 14 patients (15 lesions) with doses between 20-25 Gy. In the beta trial, 90-Sr/Y was utilized in 17 patients (17 lesions) with doses between 12-16 Gy. The QCA analysis from these studies demonstrated negative late loss and late loss index at six months for patients from the beta (-0.02 ± 0.3) and the gamma (-0.19 ± 0. 3) study. The effect of positive remodeling was maintained at 24 months, -0.16 ± 0.4 in the gamma group. Larger MLD at follow-up compared to the immediate post MLD were demonstrated in 50% of the patients from both studies. Thus, intracoronary radiation resulted in lower late loss and late loss index rates than previously reported following balloon angioplasty alone suggesting a positive vascular remodeling effect of intracoronary radiation.     

RELATIONSHIP BETWEEN ETHANOL-RELATED DISEASES AND NUTRITIONAL STATUS IN CHRONICALLY ALCOHOLIC MEN

Two-hundred and fifty chronically alcoholic men (mean age, 41± 11 years) entering an alcoholism treatment programwere studied. Detailed clinical history, nutritional assessmentand measurement of muscle strength by electronic myometer wereperformed in each case. In addition, hepatic ultrasonographyand liver biopsy, echocardiography and radionuclide cardiacscanning, and electrophysiological testing of peripheral nerveswere performed when there was clinical evidence of liver disease,cardiomyopathy or neuropathy, respectively. Alcoholic cirrhosiswas diagnosed in 20 cases, skeletal myopathy in 117, dilatedcardiomyopathy in 20 and peripheral neuropathy in 41 cases.No patients with chronic myopathy or cardiomyopathy showed eitherclinical or laboratory evidence of malnutrition. Patients withcirrhosis showed a significantly lower lean body mass than controls(P = 0.03) and significantly lower nutritional protein levelsthan those alcoholics without cirrhosis. Alcoholics with peripheralneuropathy had significantly lower anthropometric parametersand nutrition protein levels than their counter parts (P <0.001). However, in the multivariate analysis, the only independentfactor for developing these complications of alcoholism wasthe total lifetime dose of ethanol (P < 0.001). We concludethat alcohol-related diseases are common in asymptomatic alcoholicmen and these diseases appear to be due to an accumulative toxiceffect of ethanol. Age and nutritional status do not seem toplay a part in the development of such diseases.     

Protein Losing Enteropathy as a Manifestation of Henoch-Schönlein Purpura

ABSTRACT. Gastrointestinal manifestations of Henoch-Schönlein purpura (HSP) commonly include abdominal pain and gastrointestinal bleeding. Hypoproteinemia and edema could be related to renal involvement. We report a 14-year-old boy with classical features of HSP manifestated with edema due to severe intestinal protein loss, measured by elevated fecal alpha 1 antitrypsin secretion. The protein losing enteropathy subsided with corticosteroid therapy.     

Ventriculoatrial Conduction Time During Bundle Branch Reentrant Beat Initiating Orthodromic Tachycardia: A Simple and Reliable Method for Localization of Accessory Pathways

VA Interval Via Accessory Pathway During Bundle Branch Reentry. Bundle branch reentrant (BBR) complex is commonly induced during programmed ventricular stimulation with single ex-trastimulus. In patients with atrioventricular accessory pathway, BBR beat frequently triggers orthodromic tachycardia. This study was designed to determine whether evaluation of the ventriculoatrial conduction time during BBR (VA_BBR) induced with right ventricular extrastimulation (i.e., left bundle branch block morphology) can separate left free-wall (LFW) accessory pathways from left posteroseptal (LPS) or right-sided pathways. Thirty-eight patients with single atrioventricular accessory pathways were included. There were 28 men and 10 women with a mean age of 26 years. The accessory pathway was localized in LFW in 23 patients (group I) and LPS in seven (group ID. Eight patients (group III) had pathways located in the right side. In each patient, VA_BBR was determined and compared with the following: (1) V₂A₂ interval exclusively via accessory pathway; and (2) ventriculoatrial conduction time during orthodromic tachycardia with narrow QRS complex (VA_NQ), left bundle branch block plus normal axis (VA_LB-NA) or left axis (VA_LB-LA). In group I, VA_BBR values (170–245 msec, mean 196.1 ± 20.5 msec) were 0–25 msec longer than V₂A₂ (170–245 msec, mean 191.3 ± 19.1 msec) and 45–125 msec greater than VA_NQ (100–155 msec, mean 125.6 ± 14.1 msec). VA_BBR was identical to VA_LB-LA but 25–55 msec greater than VA,_LB-NA (140–205 msec, mean 160.9 ± 20.8 msec). In group II, VA_BBR values (100–140 msec, mean 118.6 ± 14.3 msec) were 15–30 msec shorter than V₂A₂ (125–165 msec, mean 140.7 ± 14.3 msec) and 15–25 msec longer than VA_NQ (85–120 msec, mean 100.7 ± 12.0 msec). Comparing VA_BBR with VA_LB-NA or VA_LB-LA did not show any statistically significant difference. In group III, VA_BBR values were consistently shorter than V₂A₂ and identical to VA_NQ. Thus, assessment of VA_BBR is a simple and useful method that can be reliably utilized to differentiate LFW pathways from LPS or right-sided pathways. Furthermore, these data provide new insights into the electrophysiological characteristics of bundle branch reentry. (J Cardiovasc Electrophysiol, Vol. 1, pp. 121–131, April 1990)     

Trisomy 3 in marginal zone B-cell lymphoma: a study based on cytogenetic analysis and fluorescence in situ hybridization

Trisomy 3 represents the most frequent and consistent chromosomal abnormality characterizing the recently defined entity marginal zone B-cell lymphoma (MZBCL). By cytogenetic analysis and/or fluorescence in situ hybridization (FISH) on interphase nuclei we found an increased copy number of chromosome 3 in 22/36 (61%) successfully analysed cases, including 8/12 cases with extranodal MZBCL, 8/13 cases with nodal MZBCL, and 6/11 patients with splenic MZBCL. Sensitivity of interphase cytogenetics was somewhat higher than that of conventional cytogenetic investigation. Structural chromosomal changes involving at least one chromosome 3 were seen in 11/20 cases with an increased copy number of chromosome 3: +del(3)(p13) was demonstrated in three cases, and was the sole chromosomal abnormality in one of them; +i(3)(q10) was seen in two other patients; and rearrangements involving various breakpoints on the long arm of chromosome 3 were found in the remaining cases. FISH on metaphase spreads confirmed these structural abnormalities and additionally showed two unexpected translocations involving chromosome 3. We conclude that: (1) trisomy 3 occurs in a high proportion of extranodal, nodal and splenic MZBCL; (2) FISH on interphase nuclei is an additional and sensitive tool in detecting an increased copy number of chromosome 3 in MZBCL; (3) additional structural abnormalities involving the long arm of chromosome 3 are frequent but non-recurrent and are perhaps secondary changes; and (4) abnormalities such as +del(3)(p13) and +i(3)(q10) suggest that genes located on the long arm of chromosome 3 are of particular importance in the pathogenesis of MZBCL.