Induced Sustained Ventricular Tachycardia in Nonischemic Dilated Cardiomyopathy: Dependence on Clinical Presentation and Response to Antiarrhythmic Agents

Thirty-one patients with nonischemic dilated cardiomyopathy either idiopathic or due to regurgitant valvular disease were studied in the cardiac electrophysiology lab. The indications for study were sustained ventricular tachycardia (VT) in 26, ventricular fibrillation (VF) in 11, and syncope of unknown etiology in 4. Sustained VT was reproducibly induced in 17 patients, including 12 with a history of sustained VT, 2 with VF and 3 with syncope. Of 15 patients undergoing serial antiarrhythmic drug studies, sustained VT was rendered noninducible or nonsustained in 23. Three had recurrent arrhythmic events while on therapy predicted to be effective. One of 2 patients discharged on a regimen predicted to be ineffective had a recurrence of sustained VT that resulted in cardiac arrest. Of 14 patients in whom sustained VT could not he reproducibly induced, 2 subsequently had spontaneous occurrences of sustained VT, and 2 experienced aborted sudden death. These results suggest the following; (1) the induction of sustained VT in the setting of nonischemic dilated cardiomyopathy is dependent on the clinical presentation; (2) antiarrhythmic drugs frequently render sustained VT noninducible or nonsustained; (3) antiarrhythmic drug suppression of inducible sustained VT predicts long-term prevention of spontaneous recurrences; and (4) noninducibility of sustained VT in the baseline state does not predict freedom from subsequent episodes of VT or sudden death.     

Soluble interleukin-6 receptor (sIL-6R), a new prognostic factor in multiple myeloma

sIL-6R is a 55 kD soluble molecule mediating the interleukin-6 (IL-6) signal through the IL-6 receptor-associated transmembrane signal transducer, gp130. It has recently been suggested that sIL-6R serum levels may reflect disease severity in multiple myeloma (MM). We determined sIL-6R serum levels in 25 normal controls (NC) and in 80 MM patients at diagnosis and during the course of the disease. Measurements were done by ELISA. In NC, sIL-6R levels ranged from 14 to 40 ng/ml (median 28 ng/ml) whereas in MM patients the range was 10–200 ng/ml (median 38 ng/ml) ( P  < 0.01). 61 patients entered remission and 19 were resistant. Median sIL-6R value at diagnosis was 36 ng/ml (10–120) in responding patients, and 82 ng/ml (20–200) in non-responding patients ( P  < 0.001). During a follow-up from 12 to 89 months, sIL-6R values remained more or less stable in most patients. High sIL-6R levels correlated with poor survival.     

Trimethylmethoxyphenyl-retinoic acid (Ro 10–1670) inhibits mitogen-induced DNA-synthesis in peripheral blood lymphocytes in vitro

Trimethylmethoxyphenyl-retinoic acid (TMMP-retinoic acid, Ro 10-1670) is the main metabolite of the aromatic retinoid Ro 10-9359 (Tigason, etretinate), which is now in clinical use. Therefore, we selected this metabolite for our in vitro studies on human lymphocytes. The following findings were obtained: TMMP-retinoic acid is practically insoluble in aqueous solution. It remains partly in solution only if bound to protein. Under these conditions it had no influence on DNA-synthesis of human peripheral blood lymphocytes added in vitro without lectins (5--12.5 ng/ml culture medium). However, if human peripheral blood lymphocytes were cultured in vitro with lectins (ConA, PHA-M, PHA-P and PWM) and in the presence of TMMP-retinoic acid (25 microgram/ml culture medium) no induction of DNA-synthesis was seen. The altered lymphocytic response in presence of TMMP-retinoid in vitro was clearly dose-dependent at these levels. Trypan blue exclusion tests showed no evidence of cytotoxicity. Our studies clearly indicate that TMMP-retinoic acid inhibits the biological response of human blood lymphocytes to lectins in vitro, at dosages close to therapeutic levels in vivo. They confirm that retinoids may exert distinct effects on dermal cells in addition to their influence on keratinocytes, and suggest that the therapeutic action of the drug may be also related to the altered lymphocytic response.     

Management of acute bleeding in a patient with congenital afibrinogenaemia

Congenital afibrinogenaemia is a rare bleeding disorder characterized by absence of fibrinogen and varying bleeding tendency. Treatment with fibrinogen concentrates is considered to be the best choice for afibrinogenaemic patients who experience bleeding. We report the case of a 22-year-old Greek patient who presented with large muscular haematomas and was treated with fibrinogen concentrates. The efficacy of this treatment and the problems that arose during his hospitalization are being discussed.     

NMR and quenched molecular dynamics studies of superpotent linear and cyclic α-melanotropins

Conformational searching, computer simulations, synthesis and NMR are used on a variety of α melanocyte-stimulating hormone (α-MSH) analogues to understand the physical characteristics required for biological potency. Peptides I (AC-[Nle⁴,Asp⁵,d -Phe⁷,Lys¹⁰]α-MSH(4-10)-NH₂), II (Ac-c[Nle⁴,Asp⁵,d -Phe⁷,Lys¹⁰]α-MSH(4-10)-NH₂) and III (Ac-[Nle⁴,Asp⁵,d -Phe⁷,Dap¹⁰]α-MSH(4-10)-NH₂ all show very similar conformational properties (backbone and side-chain torsional angles), and all display high biological potencies. The modeling results for these compounds are supported by the NMR data. Peptide IV (Ac-c[Nle⁴,Asp⁵,d -Phe⁷,Dap¹⁰]α-MSH(4-10)-NH₂) appears to have a markedly different conformation and has decreased biological potency.     

NONSEGMENTAL VITILIGO: DECREASE OF THE CD45RA+ T-CELL SUBSET AND EVIDENCE EOR PERIPHERAL T-CELL ACTIVATION

Peripheral T-lymphocytes from 16 randomly selected patients with nonsegmental vitiligo were labeled with monoclonal antibodies recognizing T-cell receptor (TCR) alpha/beta, TCR gamma/delta, CD3, CD4, CD8, CD45RA, CD45RO, CD11b, CD11c, CD16, CD56, CD25, CD54, and HLA-DR antigens. In comparison with matched controls, a significant decrease of the CD45RA+ subset (P less than 0.03) together with significant increase of the circulating HLA-DR+ cells (P less than 0.02) was found. No other alterations were detected. These findings may point to some autoimmune phenomena involved in the pathogenesis of the disease. The increased HLA-DR expression indicates the presence of activated peripheral T-cells. Thus, our data provide new and further evidence for T-cell dysregulation in nonsegmental vitiligo.     

Can Simple Doppler Measurements Estimate Interatrial Conduction Time?

COZMA, D., et al.: Can Simple Doppler Measurements Estimate Interatrial Conduction Time? Prolongation of the interatrial conduction time (ia-CT) is considered an important factor in the pathophysiology of atrial fibrillation (AF) and as a criterion to perform multisite atrial pacing. Measurement of ia-CT requires an electrophysiologic study. The aim of this study was to compare echocardiographic with electrophysiologic measurements to determine if they are correlated. Methods and Results: The study included 32 consecutive patients who underwent electrophysiologic studies. We measured ia-CT between the high right atrium and the distal coronary sinus. In all patients we measured P wave duration, left atrial diameter and area, and ia-CT by Doppler echocardiography was measured as the difference in time intervals between the QRS onset and the tricuspid A wave, and the QRS onset and the mitral A wave (DT). Ia-CT was statistically correlated with DT  (r = 0.79, P < 0.0001)  , but not with P wave duration or left atrial dimensions. Conclusions: Measurement DT may be reliable to estimate ia-CT without invasive procedure. Accordingly, DT could be used as a simple selection criterion when considering patients for atrial resynchronization therapy. (PACE 2003; 26[Pt. II]:436–439)