Optimizing the Geometry of Implantable Leads for Recording the Monophasic Action Potential with Fractally Coated Electrodes

This study investigates the influence of various lead geometry on intracardial signals like the monophasic action potential (MAP) to optimize the geometry of implantable MAP leads. The experimental results were compared with a field theoretical approach to the origin of MAP from the transmembrane potential (TAP). During the experiments several lead geometries (tip surface: 1.3 to 12 mm²; tip-ring distance: 0.8 mm to 25 cm; ring surface: 1.8mm² to 40 mm²) were investigated in endo- and epicardial positions in 12 dogs (17±9 kg). The electrodes were fixed passively (tines) or actively (screws). MAP was recorded during several interventions and correlated with MAP measured using an Ag-AgCl MAP catheter. The experimental results showed that small tips provided high MAP amplitudes with less pressure. No difference was observed using active and passive fixations. A tip-ring distance smaller than 5 mm with a ring surface smaller than the tip (<5 mm²) avoided artifacts in the repolarization course. For the theoretical approach the quasistatic, anisotropic bidomain model was calculated in smalt unity volumes V_i where the TAP φ_m was constant and represented by the current density J. Two solutions for electrode positions at and outside the heart were achieved. By superposition of each solution φ_ei the summed potential at the electrode position was calculated. The theoretical findings show in good correlation with the experimental results that a larger distance than 10 mm leads to distortions in repolarization course by signals proportional to φ_out.     

Dual Chamber Pacing in Hypertrophic Obstructive Cardiomyopathy: Beneficial Effect of Atrioventricular Junction Ablation for Optimal Left Ventricular Capture and Filling

Clinical improvement with dual chamber pacing bas largely been reported in patients suffering from hypertrophic obstructive cardiomyopathy and mainly attributed to the reduction of the subaortic pressure gradient. To be effective, pacing must induce a permanent and complete capture of the LV. In two patients of our collective, symptoms (angina and dyspnea NYHA Class III and/or syncopes) persisted or relapsed despite pacing. This was related to the inability to obtain full LV capture due to a too-short native PR interval. RF ablation of the AV junction was therefore performed in botb patients, resulting in permanent AV block in one and prolonged PR interval up to 310 ms in the second. Pacing was thereafter associated with an immediate and significant clinical improvement related to permanent LV capture, whatever the patient's activity. After RF ablation, the AV delay was set up to induce the best LV filling, as assessed by Doppler analysis of mitral flow. Our observations suggest that RF ablation or modification of the AV junction can be a successful procedure in some patients with residual or recurrent symptoms, when the latter result from a loss of capture or from the inability to program an AV delay tbat does not compromise the active component to LV filling. Doppler echocardiography is a simple and effective mean to assess the hemodynamic effect of AV interval modulation in this setting.     

Intraindividual Reproducibility of Heart Rate Variability

Heart rate variability was determined from three consecutive Holter recordings performed on days 1, 7, and 28 in 17 normal subjects, in 13 patients with angiographically normal coronary arteries, and in 9 patients with remote myocardial infarctions. Group data of several time and frequency domain measures of heart rate variability were highly reproducible (correlation coefficients 0.629–0.894). However, some individuals exhibited considerably larger day-to-day variations in heart rate variability. Single heart rate indices differed by up to 50% between two Holter recordings. Such potential differences must be considered when repeated heart rate variability determinations are used to assess changes in neurocardiac reflex regulation or effects of therapeutic interventions.     

Predicting neurological outcome following cardiac arrest

Because a large number of patients will suffer cardiac arrest each year, physicians must place attention on improving care for patients in the post-resuscitative setting. Part of this effort requires setting realistic goals based on patients' potential for recovery. Recovery from cardiac arrest often depends on the extent of anoxic brain injury, and for this reason primary teams consult neurologists to offer insight into potential for awakening from post-arrest coma. In doing so, neurologists inform a decision with legal, social and ethical implications. Though inapplicable without preparation at the time of cardiac arrest, the four principles of medical ethics have a direct impact on decision making during the post-resuscitative period. A review of the literature reveals that physical examination, electrophysiology, radiology, and biochemical markers can prove useful in estimating a patient's chances for neurological recovery from cardiac arrest. These factors most reliably predict poor outcome, but do so with high specificity. However, the role of the neurology consultant must change to include guidance on strategies of neuroprotection. Aggressive efforts directed towards neuroprotection may change predictions for outcomes after cardiac arrest in the future.     

The metabolite 1 alpha,25-dihydroxyvitamin D3 enhances lymphokine- mediated activation of the oxidative metabolism of the U937 cell line and phosphorylation of a 48-kD respiratory burst-associated protein

U937 cells respond to a variety of stimuli with increased differentiation as manifested by reduced growth, increased adherence, increased expression of several surface receptors, and increased capacity for phagocytosis and formation of reactive oxygen intermediates. In the present study the effects of lymphocyte conditioned media, recombinant interferon-gamma (IFN-gamma), and 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the ability to form reactive oxygen intermediates by U937 cells were measured by using the luminol-dependent luminescence (LDL) assay. Neither 1,25(OH)2D3 alone nor IFN-gamma alone enhanced competence for phorbol myristate acetate- stimulated LDL. Cells were capable of moderate LDL after exposure to lymphocyte conditioned media, and this was enhanced by 1,25(OH)2D3 (10(- 8) mol/L) and other vitamin D metabolites at higher concentrations. This effect was not secondary to accelerated production of myeloperoxidase, which is important in the LDL assay. Enhanced phorbol myristate acetate-stimulated phosphorylation of a 48-kd substrate was observed in 32P-labeled intact cells treated with 1,25(OH)2D3 alone or in combination with IFN-gamma. Treatment of cells with IFN-gamma or lymphocyte conditioned media did not alter phosphorylation. These results support the concept that 1,25(OH)2D3 plays a role in phagocyte differentiation and activation beyond the effects of lymphokines. Protein kinase C-mediated phosphorylation reactions may be necessary for the ability of U937 cells to reduce O2 and required for maximal activity under some conditions of incubation.     

The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy

BACKGROUND: The administration of blood components from donors who subsequently develop Creutzfeldt-Jakob disease has raised the issue of blood as a possible vehicle for iatrogenic disease. STUDY DESIGN AND METHODS: We examined infectivity in blood components and Cohn plasma fractions in normal human blood that had been "spiked" with trypsinized cells from a scrapie-infected hamster brain, and in blood of clinically ill mice that had been inoculated with a mouse-adapted strain of human transmissible spongiform encephalopathy. Infectivity was assayed by intracerebral inoculation of the blood specimens into healthy animals. RESULTS: Most of the infectivity in spiked human blood was associated with cellular blood components; the smaller amount present in plasma, when fractionated, was found mainly in cryoprecipitate (the source of factor VIII) and fraction I+II+III (the source of fibrinogen and immunoglobulin); almost none was recovered in fraction IV (the source of vitamin-K-dependent proteins) and fraction V (the source of albumin). Mice infected with the human strain of spongiform encephalopathy had very low levels of endogenous infectivity in buffy coat, plasma, cryoprecipitate, and fraction I+II+III, and no detectable infectivity in fractions IV or V. CONCLUSION: Convergent results from exogenous spiking and endogenous infectivity experiments, in which decreasing levels of infectivity occurred in cellular blood components, plasma, and plasma fractions, suggest a potential but minimal risk of acquiring Creutzfeldt-Jakob disease from the administration of human plasma protein concentrates.     

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.     

Mycobacterial Infections After Renal Transplantation

Mycobacterial infections occurred in 11 of 633 (1.7 per cent)recipients of successful renal transplants. There were no casesof tuberculosis in patients receiving chemoprophylaxis, butamongst those who did not receive prophylaxis disease occurredin six of the 27 (22 per cent) high-risk patients. The majorcause of morbidity during treatment was renal allograft rejection,largely due to reduction in immunosuppressive drug therapy.