Localization of the Origin of Arrhythmias for Ablation: From Electrocardiography to Advanced Endocardial Mapping Systems

Radiofrequency catheter ablation techniques have had a dramatic impact on the treatment of a variety of cardiac arrhythmias. However, catheter ablation of complex arrhythmias, such as intra-atrial reentry, ventricular tachycardias, and atrial fibrillation, continues to pose a major challenge. This stems from limitations of fluoroscopy and conventional catheter-based mapping techniques that limit the accurate anatomic localization of complex arrhythmogenic substrates. In this article, ECG features of complex arrhythmias are reviewed, which may facilitate the planning of an ablation procedure. The physical principles of the newly available catheter-based endocardial mapping techniques and their clinical applicability for treatment of complex arrhythmias are discussed. The role of intracardiac echocardiography to facilitate mapping and ablation is reviewed.     

Src family kinases are essential for primary aggregation by Gi‐coupled receptors

Summary. Introduction and Background: Adrenaline stimulates biphasic aggregation in plasma through the G_i‐coupled α_2A‐adrenoreceptor. In the present study, we demonstrate that both primary and secondary wave aggregation induced by adrenaline in plasma is blocked by two structurally distinct inhibitors of Src family kinases, dasatinib and PD0173952. Methods and Results: In contrast, primary aggregation is partially inhibited or unaffected in the presence of inhibitors of cyclo‐oxygenase, phosphoinositide (PI) 3‐kinases, and P2Y₁ and P2Y₁₂ ADP receptors, although secondary aggregation is abolished. The ability of adrenaline to inhibit adenylyl cyclase and to synergize with platelet agonists in mediating platelet activation in plasma is retained in the presence of Src family kinase inhibition. Moreover, adrenaline does not activate Src family kinases, as determined by western blotting of their regulatory tyrosines, suggesting that constitutive signaling from Src family kinases may underlie their role in activation. Adrenaline is widely used in clinical laboratories for investigation of patients with suspected bleeding disorders. In a group of 90 unrelated patients with a clinically diagnosed platelet bleeding disorder, we identified four who did not exhibit primary wave aggregation in response to adrenaline, although the catecholamine potentiated the response to other agonists, and five who failed to undergo secondary wave aggregation. In contrast, adrenaline stimulated biphasic aggregation in 60 controls. All of the patients with a defective response to adrenaline had impaired ADP‐induced platelet activation. Conclusions: The present results indicate a previously unappreciated role for Src family kinases in mediating G_i signaling in plasma, and demonstrate heterogeneity in response to adrenaline in patients with a clinically diagnosed platelet disorder.     

Recurrent miscarriage and antiphospholipid antibodies: prognosis of subsequent pregnancy

Summary. Background: Although women with antiphospholipid antibodies (APLAs) are at increased risk of recurrent miscarriage, the outcome of a subsequent pregnancy is not clearly elucidated. Objectives: To assess the pregnancy outcome of a subsequent pregnancy in women with APLAs and compare this outcome with women with unexplained recurrent miscarriage. Methods: We performed a cohort study among all women who attended the Miscarriage Clinic at Liverpool Women’s Hospital between 1987 and 2006 after being referred due to recurrent miscarriage (≥ 2 consecutive pregnancy losses). All women underwent a standardized investigation sequence. Women with other reasons for recurrent miscarriage were excluded. Results: A total of 693 women fulfilled the selection criteria, of whom 176 (25%) had APLAs. One hundred and twenty‐two (69%) women with APLAs had a subsequent live birth compared with 324 (63%) women with unexplained recurrent miscarriage (OR 1.3, 95% CI 0.9–1.9). No differences were found for birth weight, gestational age, and intra‐uterine growth restriction. When treatment was analyzed, 53/67 (79%) of women with APLAs who had received aspirin and heparin during their pregnancy had a live birth, compared with 64/104 (62%) of women with APLAs who received aspirin only (adjusted OR 2.7, 95% CI 1.3–5.8). In unexplained recurrent miscarriage, stratification for treatment showed no differences in outcome. Conclusion: The prognosis of a subsequent pregnancy in women with APLAs is good. Although this was not a randomized clinical trial, combined treatment of aspirin and heparin seemed associated with a better outcome in women with APLAs, but not in women with unexplained recurrent miscarriage.     

The combined use of betamethasone valerate and sodium cromoglycate in the treatment of asthma

A double-blind comparison of betamethasone valerate, sodium cromoglycate and the combination of these two treatments was carried out in twenty-two adult patients with asthma. Regular fortnightly assessments were made in the clinic throughout the study and adrenal function was monitored and found to be normal. All patients measured their peak expiratory flow rates in the morning and evening and monitored their symptoms daily on a record card as well as recording bronchodilator usage. Assessment using these parameters indicated that treatment with betamethasone valerate compared with sodium cromoglycate resulted in an improvement in the patients’ asthma which was statistically significant (P<0.001). Overall the combined treatment produced a better response than sodium cromoglycate (P<0.02) but a poorer response compared with the steroid aerosol given alone (P>0.05). In only two patients was the response to the combined therapy significantly greater than to either drug given alone.     

A surgical approch to the obturation of apically flared root canals with thermoplasticized gutta-percha

Two cases are presented in which apically flared root canals have been successfully obturated with thermoplasticized gutta-percha, following the failure of existing root fillings.