Relatively benign clinical course in asymptomatic patients with brugada-type electrocardiogram without family history of sudden death

INTRODUCTION: The incidence of sudden death or ventricular fibrillation (VF) in asymptomatic Brugada syndrome patients with a family history of sudden death is reported to be very high. However, there are few reports on the prognosis of asymptomatic Brugada syndrome patients without a family history of sudden death. METHODS AND RESULTS: Eleven patients (all male; mean age 40.5 +/- 9.6 years, range 26 to 56) with asymptomatic Brugada-type ECG who had no family history of sudden death were evaluated. The degrees of ST segment elevation and conduction delay on signal-averaged ECG (SAECG) before and after pilsicainide were evaluated in all 11 patients. VF inducibility by ventricular electrical stimulation also was evaluated in 8 of 11 patients. Patients were followed for a period of 9 to 84 months (mean 42.5 +/- 21.6). The J point level was increased (V1: 0.19 +/- 0.09 mV to 0.36 +/- 0.23 mV; V2: 0.31 +/- 0.12 mV to 0.67 +/- 0.35 mV) by pilsicainide. Conduction delay was increased (total QRS: 112.2 +/- 6.3 msec to 131.7 +/- 6.3 msec; under 40 microV: 42.0 +/- 8.5 msec to 52.7 +/- 12.7 msec; last 40 msec: 17.4 +/- 5.9 microV to 10.4 +/- 6.1 microV) on SAECG by pilsicainide. VF was induced in only 1 of 8 patients. None of the patients had syncope or sudden death during a mean follow-up of 42.5 +/- 21.6 months. CONCLUSION: This study suggests that asymptomatic patients with Brugada-type ECG who have no family history of sudden death have a relatively benign clinical course.     

Coronary angioplasty using an over-the-wire balloon catheter through a new 6 French guiding catheter.

A new 6 French (F) guiding catheter with a large, teflon-coated internal lumen (4.2F) was developed, permitting use of the standard ultralow profile (less than 3F) over-the-wire system. This small coronary angioplasty system (6F-PTCA) was evaluated in 48 lesions in 45 of 137 patients (33%) who underwent coronary angioplasty between September 1990 and January 1991. The mean age was 64 years (range 49 to 82); 37 (82%) were male. The procedure was via the brachial artery in 28 patients (62%). The overall primary success rate was 96%. It was 100% via the brachial artery and 90% via the femoral artery. There were no major complications. The puncture compression time with the 6F-PTCA via the brachial artery and via the femoral and with 8F-PTCA via the femoral was 3.8, 9.6, and 16.9 hr, respectively (P less than 0.001), although the procedure time of the 6F-PTCA via brachial and via femoral and of the 8F-PTCA was not significantly different. The mean hospital stay was 3.1, 4.5, and 5.5 days, respectively (P less than 0.01). A small hematoma occurred in 2 patients (4.4%) after the 6F-PTCA and in 3 (3.3%) after 8F-PTCA, and a large hematoma (greater than 5 cm) was noted in 7 patients (7.6%) after 8F-PTCA. These results indicate that coronary angioplasty using the over-the-wire system through the new 6F guiding catheter is technically feasible. Moreover, this approach, especially when advanced via the brachial artery, could shorten the hemostasis time and facilitate early ambulation.     

Demonstration of nucleolar organizer regions in intrahepatic bile duct carcinoma by the silver-staining technique.

A silver colloid technique to identify argyrophilic nucleolar organizer region associated protein (AgNOR) was applied to 43 cases of intrahepatic bile duct carcinoma (cholangiocarcinoma, CC), 2 with bile duct adenoma (BDA), 5 with focal duct epithelial hyperplasia (FEH) associated with hepatolithiasis, 15 with posthepatitic ductular proliferation (PHDP) associated with massive or submassive hepatic necrosis and 20 of normal liver. In the present study, only discrete, easily counted black dots within nuclei and silver-stained nucleolus were counted under a magnification of x 400 without oil-immersion objectives. The mean AgNOR count of CC was significantly higher than those of BDA, FEH, PHDP and normal controls (P less than 0.05, P less than 0.001, P less than 0.01, and P less than 0.001, respectively). Among CCs the mean AgNOR numbers of papillary adenocarcinoma (pap), moderately (tub2) and poorly differentiated (por) adenocarcinoma, and adenosquamous carcinoma (as) were significantly higher than that of normal controls (P less than 0.01, P less than 0.001, P less than 0.001 and P less than 0.001, respectively), and those of tub2, por and as were also significantly higher than those of BDA, FEH and PHDP, whereas that of well differentiated tubular adenocarcinoma (tub1) was not different from those of BDA, FEH, PHDP and normal controls, and that of pap was not different from those of BDA, FEH and PHDP. The mean numbers of AgNORs of BDA and FEH were not different from that of normal controls, whereas that of PHDP was significantly higher than that of normal controls (P less than 0.01). Interestingly, the mean AgNOR counts of tubular adenocarcinoma were increased with histologic tumor grades.(ABSTRACT TRUNCATED AT 250 WORDS)     

Limited resection based on reclassification of segment 8 of the liver

Liver vein patterns which differ from those previously described are occasionally encountered during surgery. Therefore, we reclassified the anterosuperior segment (S8) into S8v (ventral area) and S8d (dorsal area), and the right paramedian sector into the ventral segment (S8v+S5) and the dorsal segment (S8d) based on portal and hepatic vein patterns. Using this new classification, we performed three types of limited resection of S8 in six patients with neither major nor minor procedural complications including biliary leaks, and no blood transfusion. This new classification allows development of surgical procedures where resection is limited to the portal unit and tumor.     

Site-specific arrhythmogenesis in patients with Brugada syndrome

INTRODUCTION: It has been believed that electrophysiologic abnormality of the epicardial region of the right ventricular free wall may play an important role in arrhythmogenesis of phase 2 reentry in Brugada syndrome, but clinical evidence of the occurrence of ventricular arrhythmias at the right ventricular free wall has not been evaluated. In this study, we evaluated the site-specific inducibility of ventricular fibrillation (VF) and the origin of spontaneous premature ventricular contractions (PVCs) in patients with Brugada syndrome. METHODS AND RESULTS: Forty-five patients with Brugada-type ECG were enrolled in this study. Spontaneous PVCs were recorded in 9 patients. Programmed electrical stimulation (PES) was performed at the right ventricular apex (RVA), the free wall and septal region of the right ventricular outflow tract (RVOT), and the left ventricle (LV). The inducibility of PVT/VF was evaluated at each ventricular site, and the origin of PVC was determined by pace mapping. Sustained VF was induced in 17 patients. VF was induced in all 17 patients by PES at RVOT. Although PES at the septal region of the RVOT induced VF in only 5 patients (29%), PES at the free-wall region of the RVOT induced PVT/VF in 13 patients (76%). PES at RVA induced VF in only 2 patients (12%), and PES at LV failed to induce any arrhythmic events. Ventricular pace mapping showed that 64% of PVCs occurred at the free-wall region of the RVOT, 18% at the septal region of the RVOT, 9% at RVA, and 9% at LV. CONCLUSION: VF in patients with Brugada syndrome frequently is induced at the free-wall region of the RVOT area. The origin of PVC appears to be related to the site of PVT/VF induction by PES.     

Isolation and characterization of the human AKT1 gene, identification of 13 single nucleotide polymorphisms (SNPs), and their lack of association with Type II diabetes

Aims/hypothesis. AKT1, a serine/threonine protein kinase, is an important downstream target of the insulin-signalling pathway, with both anti-apoptotic and peripheral metabolic effects. Because impaired insulin signalling is a major hallmark of Type II (non-insulin-dependent) diabetes mellitus, we considered whether the AKT1 gene could be a candidate gene involved in susceptibility of this condition. To test this possibility, we isolated and characterized the human AKT1 gene. We also looked for single nucleotide polymorphisms in the gene and examined their association with Type II diabetes mellitus in the Ashkenazi Jewish population. Methods. Human BAC/P1 genomic libraries were screened to isolate the AKT1 gene. To obtain structural information and the sequences of the exon-intron boundaries, BAC/P1 clones were directly sequenced. Identification of single nucleotide polymorphisms was done by polymerase chain reaction of each exon, followed by denaturing high performance liquid chromatography. Six single nucleotide polymorphisms were genotyped in Ashkenazi Jewish patients with Type II diabetes mellitus and in control subjects. Results. The human AKT1 gene was at least 24.6 kb in length and comprised 14 exons. Altogether 13 putative intragenic single nucleotide polymorphisms, with minor-allele frequencies ranging from 0.011 to 0.354, were identified. The allelic and the genotypic frequencies of 6 single nucleotide polymorphisms were the same in diabetic patients and in control subjects. Conclusion/interpretation. The results of our studies show that the AKT1 gene is not a major contributor to susceptibility to Type II diabetes mellitus in Ashkenazi Jews. [Diabetologia (2001) 44: 910–913] Received: 18 January 2001 and in revised form: 2 April 2001     

Gait analysis in an osteoarthritis patient with restoration of the hip joint space following contralateral total hip arthroplasty: a case report

We present the case of a patient who, after undergoing unilateral total hip arthroplasty (THA), achieved pain reduction in the contralateral hip accompanied by restoration of the radiographic joint space. We conducted gait analysis to clarify the dynamic factors affecting the natural course of osteoarthritis (OA). Our findings revealed that the patient walked with exaggerated adduction of the hip following the contralateral THA, causing substantial regeneration of joint loading.     

FISH detected 11q23 microdeletion and translocation at the long arm of chromosome 11 in a child with normal karyotypic acute lymphoblastic leukemia

We report on a 6-year-old girl with acute lymphoblastic leukemia (ALL) with 11q23 microdeletion and translocation at the long arm of chromosome 11, which were detected by fluorescence in situ hybridization (FISH) but not by conventional cytogenetics. She was hospitalized because of fever and generalized bone pain. Results of peripheral blood examination included a WBC of 5,400/microliter with 12% lymphoblasts. Bone marrow studies showed 75% of early pre-B lineage lymphoblasts with L1 morphology. G-banding chromosome analysis demonstrated a normal karyotype. However, FISH using mixed lineage leukemia (MLL) and 11q subtelomere probes demonstrated 11q23 microdeletion and translocation at the long arm of chromosome 11 to an undefined chromosome. MLL rearrangement was not detected by Southern blotting analysis. The patient achieved complete remission 15 days after receiving high-risk group chemotherapy of the Kyoto University Pediatric Hematology/Oncology Study Group and has remained in complete remission for more than 30 months. Since MLL/11q23 abnormalities confer a poor prognosis in childhood ALL, the accurate detection of such abnormalities is of paramount significance in assigning individual cases to risk categories. The findings from the present case and recent literature indicate that the FISH-based approach is complementary to conventional cytogenetics, and should be systematically used in childhood ALL at diagnosis.     

Multiple initiation sites of DNA replication flanking the origin region of lambda dv genome.

Early replicative intermediates of lambda dv plasmid were prepared by an in vitro replication system in the presence of 2',3'-dideoxycytidine 5'-triphosphate, an inhibitor of DNA chain elongation. Short-chain DNAs produced from regions near the replication origin were purified from the intermediates. A fraction of the DNAs was covalently linked to primer RNA. The transition sites from primer RNA to DNA synthesis were mapped along the nucleotide sequence of the genome, by eliminating the RNA by alkaline hydrolysis and labeling the freshly exposed 5' ends of DNA with 32P. The transition sites were found to be located on both sides of the ori region, which includes four 19-base-pair repeats where one of the lambda specific initiator proteins, O, binds. No transition arose within the ori region. The transition sites are multiple on both sides of the ori region and are clustered in one of the two strands in such a way that DNA syntheses from the two sides converge. The frequency of the "leftward" DNA synthesis is several times higher than that of "rightward" synthesis, reflecting the asymmetric bidirectional replication of lambda dv DNA.