Latent atriofascicular pathway participating in a wide complex tachycardia: differentiation from ventricular tachycardia

Accessory pathways with anterograde decremental conduction properties usually are characterized by presence of antegrade preexcitation during atrial pacing. We report a 38-year-old man with frequent episodes of palpitation. No evidence of ventricular preexcitation was seen during sinus rhythm or atrial pacing. All electrophysiologic maneuvers were compatible with an antidromic tachycardia using atriofascicular pathway as the antegrade limb and the atrioventricular nodal pathway as retrograde limb. Radiofrequency ablation at recording site of accessory pathway potential resulted in cure of tachycardia with no recurrence during 3-month follow-up. This report indicated that atriofascicular pathway-mediated tachycardia should be considered in differential diagnosis of all cases of wide complex tachycardia with left bundle branch morphology and left axis.     

Treatment of experimental nephrotic syndrome with artesunate

The present study was designed to test the therapeutic effect of a new antimalarial drug, artesunate in experimental model of nephrotic syndrome. To induce this experimental model, Adriamycin was given once by a single intravenous injection (7.5 mg/kg) through the tail vein. Six days after injection of Adriamycin, therapeutic protocol was developed by intraperitoneally (IP) administration of 5 mg/kg artesunate (ARS). Total of IP injections were 14, of which 5 injections were made every day and 9 injections were carried out at regular 48-h intervals. Therapeutic protocol was terminated on day 28 and animals were killed on day 49. The results showed that treatment with ARS caused a significant reduction in the level of proteinuria, urine urea and urine sodium compared with nontreated controls. In addition, decrease in serum triglyceride and increase in the level of serum albumin was significant in treated group with ARS compared with nontreated controls. Moreover, treatment with ARS significantly reduced glomerular polymorphonuclear (PMN) and mononuclear cells infiltration, hypercellularity, karyorrhexis, wire loops, and hydropic change in capillary network within the renal cortex, as well as decreased hyalin casts. On the other hand, healthy controls receiving ARS showed a significant decrease in amounts of serum triglyceride, urine urea, and urine sodium and potassium compared with normal group. These data suggest that artesunate therapy can ameliorate proteinuria, and suppress the progression of glomerular lesions in experimental model of nephrotic syndrome; it may also be recommended as a lipid-lowering drug.     

Neuroprotective effects of bilobalide, a component of Ginkgo biloba extract (EGb 761) in global brain ischemia and in excitotoxicity-induced neuronal death

In this study, we compared the protective effect of bilobalide, a purified terpene lactone component of ginkgo biloba extract EGb 761, (definition see editorial) and EGb 761 against ischemic injury and against glutamate-induced excitotoxic neuronal death. In ischemic injury, we measured neuronal loss and the levels of mitochondrial DNA (mtDNA)-encoded cytochrome oxidase (COX) subunit III mRNA in vulnerable hippocampal regions of gerbils. At 7 days of reperfusion after 5 min of transient global ischemia, a significant increase in neuronal death and a significant decrease in COX III mRNA were observed in the hippocampal CA1 neurons. Oral administration of EGb 761 at 25, 50 and 100 mg/kg/day and bilobalide at 3 and 6 mg/kg/day for 7 days before ischemia progressively protected CA1 neurons from death and from ischemia-induced reductions in COX III mRNA. In rat cerebellar neuronal cultures, addition of bilobalide or EGb 761 protected in a dose-dependent manner against glutamate-induced excitotoxic neuronal death (effective concentration [EC (50)] = 5 microg/ml (12 microM) for bilobalide and 100 microg/ml for EGb 761. These results suggest that both EGb 761 and bilobalide are protective against ischemia-induced neuronal death in vivo and glutamate-induced neuronal death in vitro by synergistic mechanisms involving anti-excitotoxicity, inhibition of free radical generation, scavenging of reactive oxygen species, and regulation of mitochondrial gene expression.     

Patterns of drug use among young adults

The present study assessed patterns of multiple drug use among a sample of university employees and students who had been identified as having moderately high drug use habits. Use of eleven categories of legal and illegal drugs was tested and subjects reported how much of each drug they currently and habitually used. Factor analysis yielded three factors of drug use. Four of the items in the first factor (hallucinogens, cocaine, marijuana, alcohol) exhibited moderately strong and positive intercorrelations, suggesting that this particular pattern of drug use was the most common and/or reliable among young adult drug users. Sedatives and opiates were the highest loading items on the second factor, suggesting a pattern of drug use motivated by the desire for relaxation and stress avoidance. The third factor identified a pattern of legal stimulant use involving two of the three food-like categories of items employed in the present study (i.e., caffeinated cola beverages and chocolate, but not coffee). The results provided only mixed support for the hypothesis that categories of drugs with similar pharmacological properties define patterns of multiple drug use.     

Delayed cardiac perforation by one small body diameter defibrillator lead

We report a 37-year-old man who presented with continuous chest pain 6 weeks after implantable cardioverter-defibrillator implantation. Implantable cardioverter-defibrillator interrogation indicated complete loss of capture even with maximum output. Chest radiography and echocardiography confirmed extracardiac location of lead tip. After lead repositioning in electrophysiology laboratory, acceptable pacing threshold was obtained with no complication. This report demonstrates a case of delayed cardiac perforation after implantation of the St Jude Medical Durata implantable cardioverter-defibrillator lead.     

Genetic factors in lipoprotein metabolism. Analysis of a genetic cross between inbred mouse strains NZB/BINJ and SM/J using a complete linkage map approach.

A genetic cross was constructed from two parental inbred strains of mice, NZB/BINJ and SM/J, which differ markedly in their plasma lipoprotein levels. Plasma lipid and apolipoprotein values were measured in 184 F2 progeny on a normal chow diet and on an atherogenic diet. Genetic markers were typed at 126 loci spanning all chromosomes except the Y. Statistical analysis revealed significant linkage or suggestive linkage of lipoprotein levels with markers on a number of chromosomes. Chromosome 1 markers were linked to levels of total cholesterol (lod 5.9) and high density lipoprotein (HDL) cholesterol (lod 8.1), chromosome 5 markers were linked to levels of total cholesterol (lod 6.7) and HDL cholesterol (lod 5.6), and chromosome 7 markers were linked to levels of total plasma triglycerides (lod 5.1) and free fatty acids (lod 5.6). Plasma apoAII levels were linked to the apoAII gene (lod score 19.6) and were highly correlated with plasma HDL cholesterol levels (r = 0.63, P = 0.0001), indicating that apoAII expression influences HDL cholesterol levels. Molecular studies suggested that structural differences in the apoAII polypeptide of the two strains may contribute to differences in clearance of the protein.     

The frequency of spinocerebellar ataxia type 23 in a UK population

Spinocerebellar ataxias (SCA) are a genetically heterogeneous group of neurodegenerative diseases characterised by progressive cerebellar ataxia, dysarthria and oculomotor abnormalities. Recently the prodynorphin (PDYN) gene was identified as the cause of SCA23 in four Dutch families displaying progressive gait and limb ataxia. In this study we aimed to assess the frequency of PDYN gene defects and extend the phenotype of SCA23 patients in a UK ataxia series and also in patients from Greece, Egypt and India. We sequenced the coding and flanking intronic regions of the PDYN gene in a total of 852 ataxia patients, of which 356 were sporadic with no family history, 320 had a positive family history, and 176 probands had a positive family history and at least one family member had also been investigated. We also analysed 190 patients with multiple-system atrophy with cerebellar features (MSA-C), a phenocopy of SCA23. We identified a novel putative pathogenic heterozygous missense variant in the PDYN gene in an early onset SCA patient with an unknown family history. This variant was not present in 570 matched British controls. This is the first study to screen for SCA23 in UK patients and confirms that PDYN mutations are a very rare cause of spinocerebellar ataxia, accounting for ~ 0.1 % of ataxia cases but perhaps with a higher frequency in pure cerebellar ataxia. Given the rarity of PDYN mutations, front-line diagnostic evaluation of UK familial and early onset pure spinocerebellar ataxia patients should focus on other known ataxia genes.     

Electrical Storm in Patients with Implantable Cardioverter-Defibrillators: Can It Be Forecast?

The aim of this retrospective study was to determine the prevalence and predictors of electrical storm in 227 patients who had received implantable cardioverter-defibrillators (ICDs) and had been monitored for 31.7 ± 15.6 months. Of these, 174 (77%) were men. The mean age was 55.8 ± 15.5 years (range, 20–85 yr), and the mean left ventricular ejection fraction (LVEF) was 0.30 ± 0.14. One hundred forty-six of the patients (64%) had underlying coronary artery disease. Cardioverter-defibrillators were implanted for secondary (80%) and primary (20%) prevention.Of the 227 patients, 117 (52%) experienced events that required ICD therapy. Thirty patients (mean age, 57.26 ± 14.3 yr) had ≥3 episodes requiring ICD therapy in a 24-hour period and were considered to have electrical storm. The mean number of events was 12.75 ± 15 per patient. Arrhythmia-clustering occurred an average of 6.1 ± 6.7 months after ICD implantation. Clinical variables with the most significant association with electrical storm were low LVEF (P = 0.04; hazard ratio of 0.261, and 95% confidence interval of 0.08–0.86) and higher use of class IA antiarrhythmic drugs (P = 0.018, hazard ratio of 3.84, and 95% confidence interval of 1.47–10.05). Amiodarone treatment and use of β-blockers were not significant predictors when subjected to multivariate analysis.We conclude that electrical storm is most likely to occur in patients with lower LVEF and that the use of Class IA antiarrhythmic drugs is a risk factor.Key words: Antiarrhythmia agents, arrhythmias, cardiac/prevention & control, cardiac pacing, artificial, defibrillators, implantable, electric countershock, electrical storm, heart failure, tachycardia, ventricular/therapy, ventricular dysfunction, leftImplantable cardioverter-defibrillators (ICDs) have become the main therapeutic tool for use in patients with life-threatening ventricular arrhythmias.^1–3 Studies have shown that 50% to 70% of ICD patients receive appropriate device therapy within 2 years of implantation.^4,5 In most patients, the total number of delivered discharges remains low. However, some patients receive multiple appropriate shocks during a short period of time consequent to recurrent or incessant ventricular tachycardia (VT) or ventricular fibrillation (VF); either of these conditions is termed an arrhythmic or electrical storm. The delivery of multiple appropriate ICD discharges for termination of recurrent ventricular tachyarrhythmias has been reported to occur in 10% to 20% of patients, depending on the duration of the observational study period.^5–7 The prognostic implication of electrical storm is unclear: some early studies did not show increased mortality rates, but more recent trials have shown a highly significant association between electrical storm and subsequent fatal events.^6,8There are few data concerning electrical storm in ICD patients. Only a few studies have reported the incidence and clinical characteristics of electrical storm in these patients.^5–7,9,10 Consequently, the impact of antiarrhythmic therapy on subsequent events (including electrical storm) is not well understood. The aim of this study was to determine the prevalence and predictors of electrical storm in ICD patients.