ABSENCE OF EPSTEIN–BARR VIRAL ENCODED RNA (EBER) IN PRIMARY CUTANEOUS T-CELL LYMPHOMA

Epstein-Barr virus (EBV) has been associated with various extracutaneous lymphoproliferative diseases and it has been suggested that EBV may have a similar aetiological role in cutaneous T-cell lymphoma. In this study, in situ hybridization was used to investigate the presence of EBV encoded RNAs (EBER-1 and EBER-2) in 37 biopsies from 28 cases of primary cutaneous T-cell lymphoma originating from the U.K. The results showed that EBV had no demonstrable pathogenic role in the lymphomas studied, as EBER was not detected in any case.     

Molecular analysis of HLA DR4-/β1 gene in malaria vaccinees. Typing and subtyping by PCR technique and oligonucleotides

The combination of the PCR technique and the synthetic oligonucleotides has proved to be a useful tool in the molecular analysis of HLA class II genes, allowing recognition of as little as a single nucleotide modification in the sequence of the gene. The molecules encoded by these genes have been associated with genetic control of the immune response and with susceptibility to certain diseases. Studies carried out in our laboratory have shown three patterns of humoral immune response in the human volunteers vaccinated with the synthetic protein SPf 66; high, intermediate and low responders. Approximately 73.3% of the low responders were serologically typed as HLA DR4 and 42% as DQw6. These results moved us to look for a subtype (Dw) correlation between the DR4 positive individuals and the different humoral immune response patterns. Using oligo-typing methods after previous amplification of the DR4 B1 exon, we subtyped 20 DR4 volunteers, classified as high, intermediate and low responders. We did not find any direct association between the HLA DR4 Dw special subtype in the high or low responders immunized with the SPf 66 vaccine.     

New Tools for the Effective Delivery of Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) has been shown to provide symptom relief to many patients who have congestive heart failure (CHF). Still, there are technical concerns with implanting CRT systems, and these range from inadequate venous anatomy to a variety of left ventricular (LV) lead problems. Fortunately, there are several new implant tools to help physicians achieve a stable and adequate LV pacing site. There are a number of guiding catheter shapes to tailor the choice to specific anatomic abnormalities that may be encountered during implants. Key to success was the development of over-the-wire LV leads that are capable of maneuvering within complex venous anatomy. Improvements in LV leads have included increasing lead diameter and bipolar design. In some cases, epicardial LV lead placement may be necessary at surgery. The latest systems have begun to integrate disease management modalities, which hopefully will reduce the need for CHF hospitalizations.     

Wide QRS Complex Arrhythmia with Alternating QRS Morphology: What Is the Mechanism?

A 75‐year‐old man was admitted due to an electrical storm with appropriate recurrent implantable cardioverter defibrillator (ICD) discharges. The patient had had an extensive anterolateral myocardial infarction with associated severe left ventricular dysfunction 10 years earlier (left ventricular ejection fraction, 25%), and an ICD was placed 9 years before admission for primary prevention of sudden cardiac death. A first invasive study induced up to five ventricular tachycardias and an extensive endocardial substrate ablation was performed. Despite intravenous β‐blockers, general anesthesia and procainamide infusion, the patient continued to have recurrent episodes of very slow sustained ventricular tachycardia with a right bundle branch block pattern. In a subsequent invasive study, no mid‐diastolic activity was found despite careful mapping during the induced clinical ventricular tachycardia and ablation attempts inside the apical endocardial scar were unsuccessful. A percutaneous epicardial approach with navigation system support (EnSite Precision^TM Cardiac Mapping System v. 2.0, St. Jude Medical, St. Paul, MN, USA) without antiarrhythmic infusion was planned. A wide QRS complex rhythm with alternating QRS morphology was readily induced by epicardial ventricular pacing trains (Fig. 1, top) that elicited both arrhythmia QRS patterns with very long stimulus QRS intervals (Fig. 1, bottom). What is the possible mechanism of this arrhythmia? Do we need further pacing maneuvers during the arrhythmia to localize critical sites at which ablation pulses can predictably be successful?     

Dissociation of Autoaggression and Self-Superantigen Reactivity

Self-superantigens have been described as products of endogenous retroviruses of the mouse ('minor lymphocyte stimulating loci') that are capable of interacting without prior processing with conserved domains of TCR Vβ chains, causing the activation and deletion of most T cells expressing products of determined Vβ gene families [1–4], The fact that superanti-gens activate a far higher percentage of T cells (1–20%) than conventional, peptidic antigens (< 0.1 %) provides the methodological advantage that the degree of clonal deletion may be measured by the analysis of the TCR repertoire using appropriate anti-Vβ antibodies. Although much information on the spatio-temporal organization of repertoire-purging has been gathered by virtue of self-superantigens, serious doubts exist as to the possibility that such structures serve as pathogenetically relevant autoantigens. Thus, certain inbred mice spontaneously develop autoimmune diseases, although they bear T-cell repertoires that appear to be purged from self-superantigen-reactive Vβ products. In addition, therapeutic interventions targeted to Vβ gene products that are not specific for self-superantigens are successful in preventing disease development. The lack of correlation between superantigen-related Vβ deletions and autoimmune disease development is substantiated in further models of murine autoimmunity. Based on these observations, we formulate the hypothesis that self-superantigen-reactive T cells are not involved in the development of autoimmune diseases.     

The Role of Amniotic Fluid Analysis

Amniocentesis is a practical tool in daily obstetrics. The rapid and relatively safe procedure can enhance the clinician's judgement in important decisions concerning the fetal maturity, Rh iso-immunization, and genetic counseling and, to a lesser degree, in placenta localization and diagnoses of fetal well-being and congenital abnormalities. The indications and technique for amniotic fluid analysis me presented, and possible complications are discussed.