A Comparison of Intravenous Propafenone and Flecainide in the Treatment of Tachycardias Associated with the Wolff-Parkinson-White Syndrome

We compared the electrophysiological effects of intravenous propafenone andflecainide on accessory pathway conduction by a randomized crossover study in 16 patients with Wolff-Parkinson-While syndrome. The antegrade refractory period of the pathway increased from 256 ± 18 msec at baseline to 288 ± 13 msec on propafenone (P < 0.05) find to 296 ± 2 7 msec on flecainide (P = 0.075). The minimum preexcited HR interval during atrial fibrillation or incremental atrial pacing was prolonged from 225 ± 37 msec to 262 ± 22 msec by propafenone (P < 0.05) and to 301 ± 31 msec by flecainide (P < 0.005). The prolongation was significantly greater with flecainide than propafenone (P < 0.05). Both drugs increased tachycardia cycle length (TCL) from 310 ± 35 msec to 354 ± 37 msec (propafenone P < 0.005) and to 352 ± 37 msec (flecainide P < 0.01). Both propafenone and flecainide blocked antegrade conduction in the pathway in five patients. Both drugs rendered atrial fibrillation noninducifale in seven patients and orthodromic tachycardia nonindudble in five patients. Conclusions: (1) Fiecainide causes a greater prolongation of minimum preexcited RR interval than propafenone; (2) There is no significant difference between propafenone and flecainide on the inducibility of arrhythmias, TCL, or incidence of antegrade conduction block.     

Linkage of a familial platelet disorder with a propensity to develop myeloid malignancies to human chromosome 21q22.1-22.2

Linkage analysis was performed on a large pedigree with an autosomal dominant platelet disorder and a striking propensity in affected family members to develop hematologic malignancy, predominantly acute myelogenous leukemia. We report the linkage of the autosomal dominant platelet disorder to markers on chromosome 21q22. Four genetic markers completely cosegregate with the trait and yield maximum logarithm of difference scores ranging from 4.9 to 10.5 (theta = .001). Two flanking markers, D21S1265 and D21S167, define a critical region for the disease locus of 15.2 centimorgan. Further analysis of this locus may identify a gene product that affects platelet production and function and contributes to the molecular evolution of hematologic malignancy.     

Splenic lymphoma with villous lymphocytes involves B cells with extensively mutated Ig heavy chain variable region genes

Splenic lymphoma with villous lymphocytes (SLVL) is a recently defined subgroup of chronic B-cell lymphoproliferative diseases. The characteristic morphology of the tumor cells, together with phenotypic and cytogenetic findings, indicate that it is a distinct entity, but the nature of the cell or origin and its relationship to other low- grade lymphomas is unclear. For B-cell tumors, analysis of the variable region heavy chain (VH) genes used to encode the clonal Ig has shown marked differences between histologic categories, both in gene usage and extent of somatic mutation. An investigation of VH genes used in five typical cases of SLVL has shown somatic hypermutation from germline sequences in all cases, indicating that the cell of origin has been exposed to the hypermutation mechanism. However, no clonal heterogeneity was detectable, demonstrating that the tumor cell does not accumulate further mutations. These characteristics are similar to those found in mature postfollicular B cells, such as plasma cells. The distribution of mutations leading to replacement amino acids differed among the cases, with three of five cases showing clear evidence for antigen selection.     

Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency

Homocysteine can be methylated to form methionine by the cobalamin- (Cbl) and folate-dependent enzyme, methionine synthase; serum levels of total homocysteine are elevated in greater than 95% of patients with either Cbl or folate deficiency. Homocysteine can also condense with serine to form cystathionine in a pyridoxal phosphate-dependent reaction catalyzed by cystathionine beta-synthase. Cystathionine is subsequently cleaved to cysteine and alpha-ketobutyrate by the pyridoxal phosphate-dependent enzyme gamma-cystathionase. To assess levels of cystathionine in Cbl and folate deficiency, we developed a new capillary gas chromatographic-mass spectrometric assay and measured cystathionine in the serum of normal subjects and patients with clinically confirmed deficiencies of these vitamins. The normal range for serum cystathionine was 65 to 301 nmol/L (median = 126 nmol/L) for 50 normal blood donors. In 30 patients with clinically confirmed Cbl deficiency, values for cystathionine ranged from 208 nmol/L to 2,920 nmol/L (median = 816 nmol/L) and 26 (87%) had levels above the normal range. In 20 patients with clinically confirmed folate deficiency, cystathionine concentrations ranged from 138 nmol/L to 4,150 nmol/L (median = 1,560 nmol/L) and 19 (95%) had values above the normal range. Five homozygotes for cystathionine beta-synthase deficiency had high values for serum-total homocysteine and low or low-normal values for serum cystathionine that ranged from 30 nmol/L to 114 nmol/L even though they were on treatment with pyridoxine and had partially responded. One patient with a defect in the synthesis of 5-CH3- tetrahydrofolate and five patients with defects in the synthesis of CH3- Cbl had high values for serum-total homocysteine and high values for cystathionine that ranged from 311 nmol/L to 1,500 nmol/L even though they were on treatment with folic acid and Cbl, respectively, and had partially responded. We conclude that levels of cystathionine are evaluated in the serum of most patients with Cbl and folate deficiency and that they are useful in the differential diagnosis of an elevated serum-total homocysteine level.     

First Melody? valve implantations in Africa

Congenital heart lesions involving the right ventricular outflow tract (RVOT) are a common problem in paediatric cardiology. These patients need multiple surgical interventions in the form of valved conduits over a lifetime. Surgical re-valvulation was the standard treatment option until the introduction of percutaneous pulmonary valves over a decade ago. These valves can be used to prolong the lifespan of conduits and reduce the number of re-operations. The Melody® valve (Medtronic, Minneapolis, MN, USA) was introduced as the first dedicated percutaneous pulmonary valve. Percutaneous pulmonary valves can be implanted successfully and have the advantage of short hospitalisations. We describe the first three Melody® valve implantations in Africa.     

Differential expression of CD11b/CD18 (Mo1) and myeloperoxidase genes during myeloid differentiation

During the course of differentiation of early human myeloid cells toward monocytes and granulocytes, cell surface expression of the cell adhesion molecule, CD11b/CD18 (Mo1) increases dramatically and expression of myeloperoxidase (MPO), a bacteriocidal enzyme, decreases markedly. Using the inducible promyelocytic cell line HL-60 as a model, we studied the mRNA expression of these genes. Differentiation of these cells along both a monocytic and a granulocytic pathway demonstrated that the mRNA levels of the two subunits of CD11b/CD18 increased in a pattern temporally and quantitatively similar to the increase in cell surface expression of this heterodimer. In contrast, the expression of MPO mRNA decreased in a temporal and quantitative pattern similar to the known decrease in MPO protein during differentiation, suggesting that regulation of these myeloid-specific proteins may occur at the level of mRNA expression. These findings have important implications with regard to the nature of the block in differentiation in acute nonlymphocytic leukemia and the regulation of myeloid gene expression.     

Double-Pulse Defibrillation Using Pulse Separation Based on the Fibrillation Cycle Length

Double-Pulse Defibrillation Using FCL, Introduction: We investigated a method of defibrillation in which two shocks were delivered to the same electrodes with a separation hazed on the cycle length of the fibrillation event (FCL).
Methods and Results: In pentobarbital anesthetized dogs, a computerized system determined the FCL from the fibrillation event, computed the desired double-pulse (DP) shock separation, and immediately delivered the DP shocks. In group 1, energy for 50% success at defibrillation (E50) was measured using separations from 55% to 95% of the FCL and remeasured after administration of flecainide, clofilium, or vehicle to change the FCL. Both drugs increased 1(1 by = 25%. Plots of E50 versus %FCL aligned before and after drug showed that the optimum pulse separation followed the FCL. In group 2, E50s were measured for 55% to 185% FCL separations in clofilium or vehicle-treated animals. The optimum DP £50 was at 85% FCL and was not significantly different from the single-shock E50. In group 3, no differences were found when comparing the probability of success versus total energy relationships for single and optimum DP shocks. Group 4 compared E50s for single and DP shocks using a single-catheter configuration and three-electrode configurations (catheter-subdermal patch). E50s for single and DP shocks were equal using the single-catheter configuration but DP shocks required = 20% more energy in the three-electrode configurations.
Conclusion: In single-pathway lead configurations, two shocks with 85% FCL separation can be reliably combined to defibrillate using the same total energy as a larger single shock. Since the energy is unchanged but the total duration is doubled, DP shock currents are reduced by 20% to 30%.