Elimination of Ventricular Arrhythmia in Catecholaminergic Polymorphic Ventricular Tachycardia by Targeting “Catecholamine‐Sensitive Area”: A Dominant‐Subordinate Relationship between Origin Sites of Bidirectional Ventricular Premature Contractions

We report on a patient diagnosed with catechoaminergic polymorphic ventricular tachycardia (CPVT) who underwent catheter ablation of ventricular premature contractions (VPCs) induced by epinephrine. VPCs were classified roughly into three types. Type 1 and Type 2 VPCs (right bundle branch block [RBBB] configuration and inferior axis) were eliminated by radiofrequency applications at the left aortic sinus of Valsalva and the anterolateral papillary muscle (APM), respectively. Although no spontaneous VPCs were seen after the elimination of Type 1 and 2 VPCs, pacing resulting in capture at the APM induced Type 3 VPC (RBBB configuration and superior axis) reproducibly. The electrophysiological findings observed in our representative case have important implications both for understanding the pathophysiology of CPVT and for considering therapeutic strategies.     

Prevalence and Characteristics of Left Atrial Tachycardia Following Left Atrial Catheter Ablation

Background: Left atrial tachycardia (AT) is a complication of left atrial catheter ablation (LACA) of atrial fibrillation (AF). However, its prevalence and characteristics have not been sufficiently clarified.
Methods: We divided 121 patients who underwent LACA into 2 groups based on the results of AT occurrence after LACA (follow-up period; 12 ± 7 months): an AT+ group and AT– group.
Results: New-onset left AT occurred in 30 patients (25%) 31 ± 51 days after LACA. Among the 26 patients with an early onset of AT, 4 underwent a second ablation for AT, and 21 became free of AT within 6 months without a repeat ablation procedure. Among the 4 patients with a late onset of AT (>2 months after the LACA), the tachycardia remitted without a repeat ablation procedure in a single patient within 6 months. Among 71 patients who underwent LACA with additional ablation lines, 22 (31%) developed new-onset left AT. Among 50 patients who underwent LACA alone, 8 (16%) developed new-onset left AT (P = 0.02).
Conclusions: New-onset left AT is a frequent complication of LACA for AF, especially in men and in patients with a low left ventricular ejection fraction. Early (<2 months) onset AT does not require a repeat ablation because it often represents a transient phenomenon and disappears spontaneously.     

Septic pulmonary embolism due to periodontal disease

Background and objective: Septic pulmonary embolism due to periodontal disease (SPE‐PD) is rarely reported and little is known about its clinical features. The purpose of this study was to evaluate the clinical and radiological features, as well as outcome, in SPE‐PD. Methods: Patients' records were retrospectively reviewed and 12 patients with SPE‐PD were identified (10 men, mean age 60.5 years). The patients' demographic features, laboratory data, physical and radiological findings, and clinical outcomes were evaluated. Results: All but one patient were smokers. Eight of the 12 patients had comorbidities including hypertension (58%) and/or diabetes mellitus (17%). Prevalent symptoms were fever (67%) and chest pain (58%). Only two patients fulfilled the criteria of systemic inflammatory response syndrome; most of the subjects were not clinically severely ill. Blood cultures were negative in all cases. Contrast‐enhanced chest computed tomography (CT) showed multiple peripheral nodules in all 12 patients, wedge‐shaped peripheral lesions abutting on the pleura in 10 (83%) and a feeding‐vessel sign in 9 (75%). All patients recovered from their illness after antimicrobial therapy concomitant with tooth extraction or periodontal care. The median duration of antibiotic administration was 51 days. Conclusions: Most patients with SPE‐PD were not seriously ill. Contrast‐enhanced chest CT appeared to be useful to diagnose SPE‐PD.     

Skin pigmentation associated with minocycline therapy

A patient on long-term minocycline therapy developed blue-black discoloration on the legs. Skin biopsy specimens from the pigmented areas were examined by light and electron microscopy and energy-dispersive X-ray microanalysis. Pigmented granules were present at all levels of the dermis and subcutaneous fat tissues. Ultrastructural examination showed electron-dense granular material within the cytoplasm of dermal macrophages and energy-dispersive X-ray microanalysis indicated that the granules contained iron. Thyroid tissue obtained by aspiration biopsy showed the presence of fine brown granules within the cytoplasm of the follicular epithelial cells. An extract of skin from the pigmented areas was subjected to high performance liquid chromatography and minocycline was detected.     

Growth-inhibitory effects of 1,25-dihydroxyvitamin D3 on normal and psoriatic keratinocytes

The effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the growth and DNA synthesis of cultured human keratinocytes obtained from involved and uninvolved psoriatic epidermis and normal epidermis were studied. Treatment with 10(-8) M and 10(-7) M of 1,25(OH)2D3 inhibited cell growth as follows: 58.5 +/- 19.3% and 21.3 +/- 13.6% in normal keratinocytes (n = 6); 43.8 +/- 22.8% and 17.8 +/- 12.3% in psoriatic uninvolved keratinocytes (n = 4); 51.7 +/- 18.2% and 13.2 +/- 6.4% in psoriatic involved keratinocytes (n = 6). Inhibition was virtually complete at 10(-6) M. DNA synthesis was also inhibited by 10(-8) M, 10(-7) M and 10(-6) M of 1,25(OH)2D3 as follows: 70.0 +/- 8.3%, 59.0 +/- 6.8% and 16.7 +/- 4.0%, respectively, in normal keratinocytes (n = 3); 78.5 +/- 13.5%, 51.5 +/- 25.5% and 24.5 +/- 21.5%, respectively, in psoriatic uninvolved keratinocytes (n = 2); and 69.3 +/- 14.5%, 41.3 +/- 19.1% and 14.8 +/- 11.2%, respectively, in psoriatic involved keratinocytes (n = 4). These results indicate that 1,25(OH)2D3 functions as a growth inhibitor for cultured human keratinocytes derived from both normal and psoriatic skin.     

Periventricular leukomalacia associated with hypocarbia

We here report a case of periventricular leukomalacia (PVL) associated with hypocarbia which remained even after extubation. The patient had no risk factors affecting PVL development other than hypocarbia. We consider that the irregular tachypnea which remained after extubation might be attributable to overdriving of ventilation of central neurogenic origin. Our patient's clinical course suggests that sodium bicarbonate drip infusion is a very effective way to alter the set point of respiratory neuronal drive of the patient with central neurogenic hyperventilation.     

Effect of Application Volume and Area on the Absorption of Phenol Red,as a Model Drug,from the Liver Surface in Rats

To determine the influence of the method of administration of a pharmaceutical formulation we have examined the importance of application volume and area in the absorption of phenol red, as a model drug, from the rat-liver surface. When 1 mg phenol red was applied to the rat-liver surface, in-vivo, in three volumes (0.1, 0.2 or 0.334 mL) using a cylindrical glass cell (i.d. 9 mm), the shape of the plasma concentration profile differed greatly, particularly the maximum concentration. These patterns were well fitted by a two-compartment model with first-order absorption, and the absorption-rate constant K_a obtained was inversely proportional to the application volume. The absorption ratio and biliary recovery of phenol red after 6 h increased with glass cell area (i.d. 6, 9 or 14 mm; area 0.28, 0.64 or 1.54 cm²). Furthermore, the permeability coefficient P_app derived from K_a did not depend on application area, indicating no difference in the absorption characteristics of the liver surface. This also implies transport of the drug by passive diffusion from the liver surface. After intraperitoneal administration to the rat-liver surface for clinical application, increasing the application volume resulted in the delayed disappearance of phenol red from the plasma. However, the difference was not as marked as that obtained by use of the glass cell. The assumption that the effective area relating to the absorption changed with the application volume enabled us to estimate P_app. Consequently, we speculate that absorbability can be estimated precisely by consideration of application volume and area.     

Evidence for a Single Nucleotide Polymorphism in the KCNQ1 Potassium Channel that Underlies Susceptibility to Life-Threatening Arrhythmias

INTRODUCTION: Congenital long QT syndrome (LQTS) is a genetically heterogeneous arrhythmogenic disorder caused by mutations in at least five different genes encoding cardiac ion channels. It was suggested recently that common polymorphisms of LQTS-associated genes might modify arrhythmia susceptibility in potential gene carriers. METHODS AND RESULTS: We examined the known LQTS genes in 95 patients with definitive or suspected LQTS. Exon-specific polymerase chain reaction single-strand conformation polymorphism and direct sequence analyses identified six patients who carried only a single nucleotide polymorphism in KCNQ1 that is found in approximately 11% of the Japanese population. This 1727G>A substitution that changes the sense of its coding sequence from glycine to serine at position 643 (G643S) was mostly associated with a milder phenotype, often precipitated by hypokalemia and bradyarrhythmias. When heterologously examined by voltage-clamp experiments, the in vitro cellular phenotype caused by the single nucleotide polymorphism revealed that G643S-KCNQ1 forms functional homomultimeric channels, producing a significantly smaller current than that of the wild-type (WT) channels. Coexpression of WT-KCNQ1 and G643S-KCNQ1 with KCNE1 resulted in approximately 30% reduction in the slow delayed rectifier K+ current I(Ks) without much alteration in the kinetic properties except its deactivation process, suggesting that the G643S substitution had a weaker dominant-negative effect on the heteromultimeric channel complexes. CONCLUSION: We demonstrate that a common polymorphism in the KCNQ1 potassium channel could be a molecular basis for mild I(Ks) dysfunction that, in the presence of appropriate precipitating factors, might predispose potential gene carriers to life-threatening arrhythmias in a specific population.