Identification of a new cluster of T-cell receptor delta recombining elements

Within the human T-cell receptor delta (TCRD) gene we have identified a new cluster of seven delta recombining elements (deltaRec2.1-2.7), located 2.6-5.2 kilobases downstream of the Vdelta2 gene segment. The deltaRec2 elements are isolated recombining signal sequences (RSS), which were shown to rearrange with the Ddelta3 and Jdelta1 segments of the TCRD gene as well as with the psiJalpha of the TCRA gene. Rearrangements involving the deltaRec2 elements were found in all peripheral blood (PB) samples from 10 healthy individuals, although their frequency was about 100-fold lower than that of classical deltaRec rearrangements. The total frequency of deltaRec2 rearrangements was lower in PB T lymphocytes, as compared with thymocytes, suggesting that they are deleted during T-cell development. The decrease of the frequency of the deltaRec2-Ddelta3 rearrangements was most prominent: 11 times lower in PB T lymphocytes than in thymocytes. Since the deltaRec2-Jdelta1 rearrangements contained the Ddelta3 segment in the junctional region, we assume that they are derived from the deltaRec2-Ddelta3 rearrangements. In contrast, the majority of deltaRec2-psiJalpha rearrangements did not contain the Ddelta3 segment, indicating that they are single step rearrangements. The deltaRec2-Jdelta1 and deltaRec2-psiJalpha rearrangements seem to be T-lineage specific, but the deltaRec2-Ddelta3 rearrangements were also found at very low frequencies in B lymphocytes and natural killer cells. Our results suggest that deltaRec2 rearrangements are transient steps in the recombinatorial process of the TCRAD locus and are probably deleted by subsequent Valpha-Jalpha rearrangements. We hypothesize, that in a similar manner to the classical deltaRec rearrangements, the deltaRec2 rearrangements might also contribute to T-cell differentiation towards the TCR-alphabeta lineage.     

Vitamin D deficiency in the spontaneously hypertensive heart failure [SHHF] prone rat

Background and aimsVitamin D deficiency has been associated with the etiology and pathogenesis of heart disease including congestive heart failure. We previously observed cardiac hypertrophy in vitamin D deficient rats and vitamin D receptor knockout mice. These studies indicate that the absence of vitamin D-mediated signal transduction and genomic activation results in increased sensitivity of the heart to ionotropic stimuli and cardiomyocyte hypertrophy. This study's aim is to investigate the relationship between vitamin D status and the heart failure phenotype in the rat.Methods and resultsVitamin D status was assessed by measuring 25-hydroxyvitamin D levels and related to heart weight in young, middle-aged and aging spontaneously hypertensive, heart failure (SHHF) prone rats. We also measured the effects of the vitamin D hormone,1,25(OH)₂D₃, on cardiac function in SHHF rats. Cardiac hypertrophy in this model of the failing heart increased with age and related to decreasing vitamin D status. Vitamin D deficiency presented after cardiac hypertrophy was first observed. Additionally, we found that 1,25(OH)₂D₃ treatment between 4.0 and 7.0 months of age prevented cardiac hypertrophy and permits decreased workload for the heart while allowing adequate blood perfusion and pressure, resulting in reduced cardiac index.ConclusionsOur findings suggest that low vitamin D status is associated with the progression and final terminal phase of the heart failure phenotype and not with initial heart hypertrophy. Also, we report that in the vitamin D sufficient SHHF rat, 1,25(OH)₂D₃ treatment provided protection against the progression of the heart failure phenotype.     

In hospital observation of patients with acute coronary syndrome without ST elevation and multivessels coronary artery disease treated with early invasive strategy. Comparison of results of percutaneous coronary intervention and coronary artery by-pass grafting

Acute coronary syndromes (ACS) without persistent ST-segment elevation are the main cause of hospitalization, morbidity and mortality. The objective of this study was to compare clinical and angiographic parameters as well as in-hospital results of treating 307 consecutive patients with ACS without persistent ST-segment elevation with either PCI or CABG. Inclusion criteria were: rest angina within the last 24 hours, ST-segment depression (> 0.5 mm), T-wave inversion (> 1 mm) in at least two leads, positive serum cardiac markers. PCI was performed in 75.9% of patients and 24.1% of patients underwent CABG. Both groups did not differ as to age, sex, history of diabetes, arterial hypertension, heart failure, smoking and ejection fraction. Positive troponin was significantly more frequent in the PCI group. 51% of PCI patients and 80% of CABG patients had complete revascularization (p = 0.00001). Independent predictors of in-hospital death in the CABG group were: inability to determine culprit vessel during coronary angiography due to lesions' severity (OR 13.65; 95% CI 9.40-15.20; p = 0.007) and heart failure (OR 15.58; 95% CI 12.29-18.01; p = 0.003). In the PCI group these independent predictors were: Braunwald's IIIC unstable angina (OR 5.48; 95% CI 3.10-7.17; p = 0.04) and diabetes (OR 2.22; 95% CI 1.07-3.90; p = 0.003). In-hospital mortality rate was significantly higher in the CABG group (8.1% vs 1.7% p < 0.01). Patients with multivessel coronary artery disease and ACS without ST-segment elevation treated with PCI have better in-hospital outcome than patients assigned to CABG, but the rate of complete revascularization is lower.     

A case report of a patient with dermatomyositis as a prodromal sign of lung cancer

Dermatomyositis (DM) is a connective tissue disease characterized by specific inflammatory lesions in muscle biopsy. It is caused by vasculitis determined by humoral factors with subsequent inflammatory cell accumulation, mainly T CD4+ and B cells, which infiltrate myocytes leading to its vacuolization and degeneration (mainly in the skeletal muscles, rarely in the smooth muscles). The incidence of DM is estimated at 1-10 per million in adults and at 1-3.2 per million in children. The autoimmune mechanism of disease induction is not fully recognized. Several lines of evidence showed the link between DM and neoplastic disease. The first report of dermatomyositis associated with stomach cancer, by Stertz, comes from 1916. In the same time, Kankeleit reported DM associated with breast cancer. Presumably, it is the result of immune reaction against antigens common for muscle and neoplastic cells or some paraneoplastic syndrome underlying mechanism. The report presents the case of a 52-year-old woman with DM (diagnosed according to the Bohan and Peter criteria) and with coexistent squamous lung cancer in situ. The left upper lobectomy was performed. No complications in postoperative period were observed. During more than 2 years of follow-up after the surgery, the patient remained in good condition, without DM symptoms, or cancer relapse. Considering that DM may be associated with lung cancer; extensive diagnostic work-up to exclude neoplastic lesions should be performed. Patients aged 40 years or more should be particularly screened.     

Molecular characterization of illegitimate TCRδ gene rearrangements in acute myeloid leukaemia

SUMMARY. Recently, we and others have shown the occurrence of TCRδ gene rearrangements in acute myeloid leukaemia (AML). In this study we describe the molecular characteristics of these rearrangements by the polymerase chain reaction (PCR) and the direct sequencing of PCR products. 11 rearrangements were characterized in blast cell samples from six patients. We found a heterogenous pattern of TCRδ gene rearrangements with involvement of Vδ1-5 regions. These findings differ from observations in T-ALL and B-cell precursor ALL, where predominantly usage of Vδ1 and Vδ2 regions has been described. Furthermore, extensive diversity of junctional sites was observed, including addition of up to 37 N nucleotides, nucleotide deletions at junction sites of Vδ and Jδ segments and usage of up to three Dδ segments. The Dδ3 fragment was the most frequently used diversity element and was found in 10 rearrangements. Nine of the 11 rearrangements were non-functional, either incomplete or out of the reading frame. Therefore a functional TCRδ cannot be expressed in these myeloid blast cells.     

Risk of thromboembolic complications in patients with permanent atrial fibrillation undergoing cardioverter-defibrillator implantation

BACKGROUND: Cardioversion of atrial fibrillation (AF) carries the risk of thromboembolic complications and, therefore, anticoagulation therapy is routinely administered before and after this procedure. In patients with permanent AF who undergo implantation of cardioverter-defibrillator (ICD), anticoagulants are usually withdrawn during the perioperative period. However, in some patients sinus rhythm may be restored during defibrillation threshold (DFT) testing which potentially may increase the risk of thromboembolic complications. AIM: To assess the frequency of sinus rhythm restoration during ICD implantation in patients with permanent AF and the rate of both thromboembolic events and local bleeding complications which may occur due to temporary withdrawal of anticoagulation therapy and its re-initiation early after the procedure. METHODS: Permanent AF was present in 23 (12%) of 193 patients selected for ICD implantation. All patients received prolonged oral anticoagulation according to the generally accepted standards. Anticoagulation therapy was stopped few days before the procedure and replaced by low molecular weight heparin which was administered up to 24 hours before ICD implantation and re-initiated 12-24 hours afterwards. RESULTS: During DFT testing sinus rhythm was restored in 5 (21.7%) patients with AF. Clinical and DFT characteristics were similar in those who were converted to sinus rhythm and those who remained in AF. No thromboembolic events were noted in either group. Local haematoma at the site of ICD implantation occurred in two (8%) patients. CONCLUSIONS: Sinus rhythm was restored in 21.7% of patients with permanent AF who underwent ICD implantation. Temporary withdrawal of anticoagulation therapy did not increase the risk of thromboembolic complications, however, its early re-initiation after implantation resulted in an increase in local bleeding complication rate.     

Clinical efficacy of amiodarone as an antiarrhythmic agent

Amiodarone, administered orally in doses of 200 to 600 mg/day, was remarkably effective in the treatment and prevention of a wide variety of atrial and ventricular arrhythmias. Total suppression and control was provided in 98 (92.4 percent) of 106 patients with supraventricular arrhythmias and in 119 (82 percent) of 145 patients with ventricular arrhythmias. The rates of total control of the arrhythmia were: 96.6 percent in 30 patients with recurrent atrial flutter or fibrillation, 96.6 percent in 59 patients with repetitive supraventricular tachycardia, 100 percent in 27 patients with Wolff-Parkinson-White syndrome and 77.2 percent in 44 patients with recurrent ventricular tachycardia unsuccessfully treated with other drugs. Excellent results were obtained in 6 of 8 patients with repetitive ventricular tachycardia and ventricular fibrillation related to postinfarction ventricular aneurysm and in 12 of 14 patients with ventricular extrasystoles and ventricular tachycardia related to Chagasic myocarditis. Amiodarone proved safe in patients with severe congestive heart failure and severe myocardial damage. Its clinical efficacy was related to its electrophysiologic properties and to two unique properties: its wide safety margin and its cumulative effect. The latter liberates patients from a rigid hourly schedule and provides for continuous antiarrhythmic control, days and even weeks after treatment is discontinued.     

Existence of automaticity in anomalous bundle of Wolff-Parkinson-White syndrome.

Escape beats probably arising from the anomalous bundle were documented in 2 patients with the Wolff-Parkinson-White (WPW) syndrome. A third patient, in whom complete AV block developed both in the anomalous bundle and the normal pathway, showed the occurrence of escape beats (an escape-bigeminy pattern), as well as a regular idioventricular rhythm arising from the anomalous bundle. Phase 4 block in the anomalous bundle occurred in 7 other patients, in 4 of them spontaneously and in 3 only after the administration of ajmaline or amiodarone. Only 4 of 14 fully investigated patients (out of a total number of 23) showed absence of both escape beats and phase 4 block. The escape beats were considered as direct evidence, and the phase 4 block as indirect evidence, for the existence of automaticity in the anomalous bundle. Such evidence supports the view that the anomalous bundle, like the His bundle-branch system, may be composed of specialised tissue endowed with the property of automaticity.     

Successful RF ablation of permanent VT in a patient with acute coronary syndrome treated by complex angioplasty and stent implantation

We describe a case of a 59-year-old male with permanent VT in the course of an acute coronary syndrome. Coronary angiography revealed acute occlusion of the right coronary artery. Although the underlying condition was treated by implantation of 4 stents with excellent haemodynamic effect (TIMI 3), the tachycardia continued, being refractory to drugs (amiodarone). The attempts to restore sinus rhythm by DC electrical cardioversion or transvenous pacing were unsuccessful. The patient was referred to the EP lab. A critical isthmus localised at the paraseptal region of the LV and parallel to the mitral annulus was identified. The isthmus was closed by linear RF application, resulting in VT termination. Due to impaired LV ejection fraction (<30%) the patient was scheduled for ICD implantation. During 6-week follow-up the patient remained free of arrhythmia.