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.     

Decreased levels of T-cells and cells with suppressor T-cell phenotype as defined by specific monoclonal antibodies in patients with atopic dermatitis

peripheral blood cells from forty patients with atopic dermatitis and elevated serum IgE levels were studied by indirect immunofluorescence using monoclonal antibodies OKT3, OKT4, OKT8 to, respectively, human T cells, helper-inducer and suppressor-cytotoxic T cell subsets. Decreased T cells with the suppressor-cytotoxic phenotype, with an abnormal balance between helper and suppressor cell subsets, and decreased peripheral blood T cells counts were found as compared to controls. Results were similar in the three age-matches group (4 months–2 years, 2–15 years, 15–50 years) studied. No correlation could be established between serum IgE levels and the elevated helper/suppressor cell ratios.     

Role of Amiodarone in the Era of the Implantable Cardioverter Defibrillator

Amiodarone is one of the most frequently used antiarrhythmic drugs in clinical practice. In patients with atrial fibrillation, in whom rhythm control is judged desirable, amiodarone is the most effective therapy. Amiodarone effectively prevents atrial fibrillation and may improve quality of life, but there is no evidence that it decreases mortality or severe morbidity in atrial fibrillation. In patients at risk for life-threatening ventricular arrhythmias, amiodarone may decrease mortality to a small degree, but the evidence for this benefit is incomplete. Patients with implantable cardioverter defibrillators frequently require antiarrhythmic drug therapy, especially to treat electrical storm. Amiodarone is useful in these patients; however, it may increase defibrillation thresholds in some patients. In patients with out-of-hospital DC shock-resistant VF, amiodarone is the most effective antiarrhythmic drug available to assist in resuscitation. Amiodarone is a complicated drug, and its optimal use requires careful patient surveillance with respect to potential adverse effects. (J Cardiovasc Electrophysiol, Vol. 14, pp. S78-S81, September 2003, Suppl.)     

Molecular detection of t(8;21)/AML1-ETO in AML M1/M2: correlation with cytogenetics, morphology and immunophenotype

The t(8;21) identifies a subgroup of acute myeloid leukaemia (AML) with a relatively good prognosis which may merit different treatment. It is associated predominantly, but not exclusively, with AML M2, and corresponds to rearrangements involving the AML1 and ETO genes. AML1-ETO positive, t(8;21) negative cases are well recognized but their incidence is unknown. In order to determine optimal prospective AML1-ETO RT-PCR screening strategies, we analysed 64 unselected AML M1 and M2 cases and correlated the results with other biological parameters. Molecular screening increased the overall detection rate from 8% to 14%. AML1-ETO was found in 3% (1/32) of AML M1 and 25% (8/32) of M2, including three patients without a classic t(8;21) but with chromosome 8 abnormalities. It was more common in younger patients. Correlation with morphology enabled development of a scoring system which detected all nine AML1-ETO-positive cases with a false positive rate of 7% (4/55). Although certain AML1-ETO-positive cases demonstrated characteristic immunological features (CD19 and CD34 expression, CD33 negativity), each of these markers was insufficiently specific to permit prediction in an individual case. We conclude that initial routine prospective molecular screening for AML1-ETO in all AMLs, combined with standardized morphological and immunological analysis, is desirable in order to produce improved prognostic stratification and to determine whether screening can ultimately be restricted to appropriate subgroups.     

Canadian Registry of ICD Implant Testing Procedures (CREDIT): Current Practice,Risks, and Costs of Intraoperative Defibrillation Testing

Defibrillation Testing at ICD Implantation. Background: There is uncertainty about the proper role of defibrillation testing (DT) at the time of implantable cardioverter defibrillator (ICD) insertion. Methods: A prospective registry was conducted at 13 sites in Canada between January 2006 and October 2007. Objectives: To document the details of DT, the reasons for not conducting DT, and the costs and complications associated with DT. Results: DT was conducted at implantation in 230 of 361 patients (64%). DT was more likely to be conducted for new implants compared with impulse generator replacements (71% vs 32%, P = 0.0001), but was similar for primary and secondary prevention indications (64% vs 63%, P = NS). Among patients not having DT, the reason(s) given were: considered unnecessary (44%); considered unsafe, mainly due to persistent atrial fibrillation (37%); lack of an anesthetist (20%); and, patient or physician preference (6%). When performed, DT consisted of a single successful shock ≥ 10J below maximum device output in 65% of cases. A 10J safety‐margin was met by 97% of patients, requiring system modification in 2.3%. Major perioperative complications occurred in 4.4% of patients having DT versus 6.6% of patients not having DT (P = NS). ICD insertion was $844 more expensive for patients having DT (P = 0.16), largely due to increased costs ($28,017 vs $24,545) among patients having impulse generator replacement (P = 0.02). Conclusions: DT was not performed in a third of ICD implants, usually due to a perceived lack of need or relative contraindication. (J Cardiovasc Electrophysiol, Vol. 21, pp. 177‐182, February 2010)     

INVERSE CORRELATION BETWEEN EXPRESSION OF HLA-B AND c-myc IN UVEAL MELANOMA

HLA class I is expressed in 75–85 per cent of uveal melanoma and cytoplasmic c- myc expression has been reported in 78 per cent of uveal melanoma. In skin melanoma, an inverse relationship has been observed between HLA class I expression and c- myc . The purpose of this study was to determine whether a similar correlation occurred between high expression of c- myc and low expression of HLA class I in uveal melanoma. The expression of c- myc , HLA-A, and HLA-B was determined by immunohistochemistry on formalin-fixed and paraffin-embedded sections of 30 uveal melanomas. Cell cultures from four primary uveal melanomas (lines 92-1, MEL 202, OCM-1, and EOM-3) and one uveal melanoma metastasis (line OMM-1) were tested for mRNA levels of c- myc and HLA-A and HLA-B in Northern blot assays. The high level of expression of cytoplasmic c- myc was significantly correlated with low expression of HLA-B ( P =0·03) and vice versa. High expression of HLA-B was significantly correlated with the presence of epithelioid cells ( P =0·004). The inverse correlation observed between c- myc and HLA-B expression is similar to previous observations in cutaneous melanoma. By downregulating HLA-B expression, c- myc may influence the immune response in uveal melanoma. Tumours containing epithelioid cells showed a significantly higher expression of HLA-B than tumours of the spindle cell type. © 1997 by John Wiley & Sons, Ltd.     

Angiographic Anatomy of the Coronary Sinus and Its Tributaries

Permanent left ventricular pacing has been shown to imporve the hemodynamic and clinical status of patients with severe heart failure. To pace the left ventricle, the electrode is implanted in tributaries of the coronary sinus (CS). However, the anatomy of cardiac veins with this purpose in mind has not been described in detail. Methods: One hundred consecutive patients admitted for coronary angiography had a simultaneous coronary venography performed after the injection of 8 to 10 mL of contrast material into the left coronary artery. Cardiac veins were analyzed in antero-posterior, left anterior oblique 60±, and right anterior oblique 30± views by three different observers. The number, dimension, angulation, and position of the coronary sinus and of its tributaries were studied. Results: Two veins are consistently present: the middle cardiac vein (mean diameter 2.62 ± 1.26 mm) and the great cardiac vein (mean diameter 3.55 ± 1.24 mm). The left posterior vein(s) (LPV) (mean diameter 2.25 ± 1.2 mm) is (are) variable in number (ranging from 0 to 3), size, and angulation. The absence of LPV limits the ability to pace the left ventricle endovenously. The diameter of the vein (< 2 mm) and its angulation may also complicate the insertion of the lead. Conclusion: Angiographic analysis of dimensions, tortuosity, number, and angulation of venous tributaries of the CS seems to allow the insertion of commercially available pacing leads in approximately 85% of cases. An increase in this percentage hinges on the development of new, dedicated leads.     

A population survey of bowel habits in urban Swiss men

The aim of this study was to determine the prevalence of symptomsrelated to constipation in urban Swiss men and to identify associatedsociodemographic factors and health habits. A sample of 773men aged between 35 and 74 years randomly selected from theGeneva population answered a questionnaire on bowel habits duringa personal interview in a mobile epidemiological unit. ‘Constipation’was reported by more than 6% of subjects, difficulties in stoolevacuation by approximately 5% and less than three stools perweek by approximately 2%. These symptoms appeared less prevalentin subjects with post-baccalaureate education (the excess prevalenceof self-reported constipation, difficulty in stool evacuationand frequent daily defecation was greater than 5%). Smokerswere more likely to have a frequency of 3–7 stools perweek and were less affected by frequent daily defecation. Self-reportedconstipation was more prevalent in subjects with a higher dietaryfibre intake. No statistically significant effects of age, nationality,dietary fat or physical activity were observed. These resultsare consistent with national surveys in US populations. Factorsrelated to socioeconomic status or education may be a causeof constipation in men, but they still need to be elucidated.