A COMPARATIVE STUDY OF T-CELL DEPLETED AND NON-DEPLETED MARROW TRANSPLANTATION FOR HEMATOLOGICAL MALIGNANCY

Sixteen patients with hematological malignancy received cyclophosphamide (120 mg/kg), fractionated total body irradiation (12 Gy), oral cyclosporin, and an HLA-identical sibling marrow transplant depleted of T cells by incubation with the monoclonal antibody anti-HuLy-m1 (CD2) and rabbit complement with (five patients) or without (11 patients) anti-HuLy-m8 (CD8). These 16 patients were compared historically to 84 patients with hematological malignancy receiving cyclophosphamide (120 mg/kg), fractionated total body irradiation (12 or 14 Gy), oral cyclosporin, and unmanipulated HLA-identical sibling marrow, for parameters of engraftment and graft-versus-host disease (GVHD). Graft failure occurred in one of the 16 T-cell depleted recipients and in one of the 84 non-depleted recipients. Engraftment was slightly but significantly slower in the T-cell depleted group and bacterial infections significantly more, frequent and severe than in the unmanipulated group. There was a suggestion that the severity of acute GVHD was reduced in those receiving T depleted marrow. Randomized trials will be necessary to determine if marrow T-cell depletion results in superior long-term leukemia-free survival.     

VJ REARRANGEMENTS OF THE TCRγ LOCUS IN PERIPHERAL T-CELL LYMPHOMAS: ANALYSIS BY POLYMERASE CHAIN REACTION AND DENATURING GRADIENT GEL ELECTROPHORESIS

Using Southern blotting for the diagnosis of clonality in peripheral T-cell lymphomas (PTCLs), analysis of the T-cell receptor (TCR) γ gene rearrangement was shown to be more informative than that of the TCR β gene rearrangement. In order to amplify every VJγ rearrangement, a polymerase chain reaction (PCR) procedure using newly designed GC-clamp primers has been developed. All primers can be mixed in a single multiplex PCR. PCR products are analysed by denaturing gradient gel electrophoresis (DGGE), providing tumour-specific imprints inasmuch as the procedure characterizes N sequence polymorphism at the VJ junctions. In a series of 30 PTCL cases, the PCR procedure demonstrated 27 cases to be clonally rearranged and failed in three cases. PCR was more accurate than Southern blotting, showing 47 rearranged γ alleles, four of which were undetectable on the Southern blot. When lymphomas were studied at different sites and at relapse, the DGGE pattern remained unchanged. In PTCL, the proposed PCR is helpful for the diagnosis and staging of the disease and should improve the follow-up monitoring. The undetectability of clonal rearrangements in a few cases is discussed in the light of concepts of lymphomagenesis and T-cell differentiation.     

Preduodenal portal vein with situs inversus and duodenal atresia

In a 7-day-old infant referred because of bile-stained vomiting, jaundice and lack of meconium, radiological examination revealed the 'double-bubble' sign of duodenal atresia as well as dextrocardia. This infant also had a strawberry haemangioma on the right shoulder. Operation disclosed situs inversus and a preduodenal portal vein as well as duodenal atresia. A side-to-side duodeno-jejunostomy was performed successfully without damage to the anomalous vein. The history of polyhydramnion during gestation, the presence of other anomalies, the rapid onset of bile-stained vomiting and the classic 'double-bubble' sign, together appeared to indicate that the duodenal atresia was intrinsic and not due to the external pressure of the anomalous vein on the duodenum.     

Vagal Paroxysmal Atrial Fibrillation: Prevalence and Ablation Outcome in Patients Without Structural Heart Disease

Prevalence of Vagal Paroxysmal Atrial Fibrillation . Introduction: The prevalence of vagal and adrenergic atrial fibrillation (AF) and the success rate of pulmonary vein isolation (PVI) are not well defined. We investigated the prevalence of vagal and adrenergic AF and the ablation success rate of antral pulmonary vein isolation (APVI) in patients with these triggers compared with patients with random AF. Methods and Results: Two hundred and nine consecutive patients underwent APVI due to symptomatic drug refractory paroxysmal AF. Patients were diagnosed as vagal or adrenergic AF if >90% of AF episodes were related to vagal or adrenergic triggers; otherwise, a diagnosis of random AF was made. Clinical, electrocardiogram (ECG), and Holter follow‐up was every 3 months in the first year and every 6 months afterward and for symptoms. Of 209 patients, 57 (27%) had vagal AF, 14 (7%) adrenergic AF, and 138 (66%) random AF. Vagal triggers were sleep (96.4%), postprandial (96.4%), late post‐exercise (51%), cold stimulus (20%), coughing (7%), and swallowing (2%). At APVI, 94.3% of patients had isolation of all veins. Twenty‐five (12%) patients had a second APVI. At a follow‐up of 21 ± 15 months, the percentage of patients free of AF was 75% in the vagal group, 86% in the adrenergic group, and 82% for random AF (P = 0.51). Conclusion: In patients with PAF and no structural heart disease referred for APVI, vagal AF is present in approximately one quarter. APVI is equally effective in patients with vagal AF as in adrenergic and random AF. (J Cardiovasc Electrophysiol, Vol. 21, pp. 489‐493, May 2010)     

Mucosal pharmacokinetics and pilot study of short course of parenteral imipenem in the eradication of Helicobacter pylori

Abstract Eradication of Helicobacter pylori infection is known to reduce the incidence of duodenal ulcer recurrence. The most commonly used regimen for H. pylori infection is triple antimicrobial therapy for 1-2 weeks. This treatment is associated with frequent side effects and hence unsatisfactory compliance. As in vitro data showed that H. pylori is sensitive to imipenem, the pharmacokinetics of this drug in the gastric milieu, and the clinical efficacy of imipenem with omeprazole in eradicating H. pylori infection were studied. Imipenem/cilastatin levels in serum, gastric secretion and gastric mucosa were assayed in four patients after intravenous injection of a bolus dose of 500 mg. The serum and gastric secretion levels of imipenem achieved were more than 10 times the minimum inhibitory concentration of the drug for H. pylori. Gastric mucosal levels of imipenem vary considerably with time, which probably indicates rapid elimination of the drug into the gastric lumen. In the second part of this study, imipenem/cilastatin was given intravenously for the first 2 days after diagnosis of H. pylori infection in patients with endoscopically confirmed duodenal ulcers. The patients were also treated with 4 weeks of omeprazole. Clearance of H. pylori was initially achieved at the end of 2 days in 20 out of 22 (91%) patients. However, when the biopsies were repeated at 8 weeks, recurrence of H. pylori infection was evident in 19 cases (86.3%) indicating a failure of eradication. It was concluded that imipenem/cilastatin in combination with omeprazole failed to eradicate H. pylori infection.     

Diagnosis and Ablation of Multiform Fascicular Tachycardia

Ablation Multiform Fascicular Tachycardia . Introduction: Fascicular tachycardia (FT) is an uncommon cause of monomorphic sustained ventricular tachycardia (VT). We describe 6 cases of FT with multiform QRS morphologies. Methods and Results : Six of 823 consecutive VT cases were retrospectively analyzed and found attributable to FT with multiform QRS patterns, with 3 cases exhibiting narrow QRS VT as well. All underwent electrophysiology study including fascicular potential mapping, entrainment pacing, and electroanatomic mapping. The first 3 cases describe similar multiform VT patterns with successful ablation in the upper mid septum. Initially, a right bundle branch block (RBBB) VT with superior axis was induced. Radiofrequency catheter ablation (RFCA) targeting the left posterior fascicle (LPF) resulted in a second VT with RBBB inferior axis. RFCA in the upper septum just apical to the LBB potential abolished VT in all cases. Cases 4 and 5 showed RBBB VT with alternating fascicular block compatible with upper septal dependent VT, resulting in bundle branch reentrant VT (BBRT) after ablation of LPF and left anterior fascicle (LAF). Finally, Cases 5 and 6 demonstrated spontaneous shift in QRS morphology during VT, implicating participation of a third fascicle. In Case 6, successful ablation was achieved over the proximal LAF, likely representing insertion of the auxiliary fascicle near the proximal LAF. Conclusions : Multiform FTs show a reentrant mechanism using multiple fascicular branches. We hypothesize that retrograde conduction over the septal fascicle produces alternate fascicular patterns as well as narrow VT forms. Ablation of the respective fascicle was successful in abolishing FT but does not preclude development of BBRT unless septal fascicle is targeted and ablated. (J Cardiovasc Electrophysiol, Vol. 24, pp. 297‐304, March 2013)     

Assessing the knowledge and skill needs of community-based health promoters

Community-based health promoters require a range of complexskills. As part of its ongoing support to five community-basedhealth promotion programs, the Health Promotion Branch of theOntario (Canada) Ministry of Health, commissioned a study toidentify knowledge and skills needs in these programs and assesswhether resources were available to meet these needs. A NeedsAnalysis Questionnaire was developed and administered to coordinators,staff board members, and volunteers at 23 health promotion sites.Key informant interviews with site coordinators and focus groupinterviews of site staff board members and volunteers were carriedout. The needs analysis process is presented, as are illustrativefindings. Potential applications of the needs analysis proceduresare considered.     

Adolescent resilience: The potential impact of personal development in schools

Abstract The challenges and stresses faced by adolescents include entry into secondary school, the development of adolescent sexuality, family conflicts, parental mental illness, socio-cultural factors, substance use and abuse, work and career abuse, social and antisocial behaviour, and the carry-over of problems from childhood. The ways in which programmes through schools can address these issues, enhance resilience and promote adolescent mental health are discussed. The potential of personal development programmes could be utilized to this end, with targeted educational and group initiatives and evaluation of outcomes.