Inadequate Erythropoietin Response to Anaemia in HIV Patients: Relationship to Serum Levels of Tumour Necrosis Factor-Alpha, Interleukin-6 and Their Soluble receptors

Severe anaemia is a frequent complication in advanced HIV infection. In our study we investigated the interaction between cytokine network, HIV infection and erythropoietin (Epo) response with increasing anaemia levels. No correlations could be established between circulating tumour necrosis factor (TNF)-alpha and any of the examined parameters. However, a negative correlation was found between haemoglobin values and soluble TNF receptor levels (sTNF-R-I: r  = −0.54; P  < 0.001; sTNF-R II: r  = −0.47; P  < 0.001) as well as interleukin-6 levels ( r  = −0.29; P  < 0.001). In contrast, no significant increase in log[Epo], counterbalancing haemoglobin decline and paralleling the rise in sTNF receptors, was found. In patients classified as stage III, according to the Centers for Disease Control (CDC) classification, the erythropoietin response was significantly more impaired than in patients from CDC groups I and II ( P  < 0.001). The results of this study suggest that similar to its action in vitro , activation of the TNF/TNF-R system may impair erythropoietin production in HIV-associated anaemia. Due to the brief half-life of TNF-α, this activation is particularly reflected by elevations of soluble TNF receptor levels.     

Acute Efficacy and Chronic Follow-Up of Patients with Non-Thoracotomy Third Generation Implantahle Defibrillators

Non-thoracotomy implantation of implantable cardioverter defibrillators (ICDs) has simplified the process of device inserfion, promising to decrease associated procedural coniplications while providing sudden death protection at least equal to epicardial systems. This study presents the acute and chronic results of 110 patients who underwent attempted non-thoracotomy ICD impiuntation wiih the Medtronic Transvene lead system and PCD model 7217 or 7219. Of the 110 patients attempted, 100 (91%) had the system successfully implanted without the need for an epicar-dial patch. One patient died 1 week postoperatively of septic shock related to the implantation (0.9% perioperative mortality). During folloiv-up of 16 ± 11 months, 45% of the patients had an event detected as ventricular tachycardia; 26% of these detections were felt clinically to be due to supraventricular rhythms. Of the remainder, 87% were successfully treated with the first VT therapy, and 98% were terminated by the final therapy; 66% of the patients had at least one episode of ventricular fibrillation, of which 5% were felt to be inappropriate detections; 65% of the appropriate episodes were successfully treated with the first VF therapy, and all were converted by the final therapy. Total mortality at 6, 12, and 24 months was 3%, 11%, and 19% respectively. Only one patient had sudden cardiac death, occurring at 13 months postimplant. Overall, the non-thoracotomy lead system for this ICD displayed infrequent implant complications and proved to be reliable ai terminating arrhythmias and maintaining a low rate of sudden cardiac death in this high risk popuiation.     

Embryotoxicity Study of Monomeric 4,4'-Methylenediphenyl Diisocyanate (MDI) Aerosol after Inhalation Exposure in Wistar Rats

One of the uses of MDI is as an alternative to formaldehydein the manufacture of furniture, its main route of exposureto humans being by inhalation. There have been no previous studieson the potential prenatal toxic effects of this compound. Toclose this gap in information, gravid Wistar rats, Crl:(WI)BR,were exposed by whole-body inhalation to clean air (control)and to 1, 3, and 9 mg/m3 MDI, respectively, for 6 hr per dayfrom Days 6 to 15 post conception (p.c). Rats were killed onDay 20 p.c. and the following results were obtained: Treatmentcaused a dose-dependent decrease in food consumption in allsubstance-treated groups during exposure, returning to normalvalues after cessation of treatment. The lung weights in thehigh-dose group were significantly increased compared to thesham-treated control animals. Treatment did not influence anyother maternal and/or fetal parameters investigated (maternalweight gain, number of corpora lutea, implantation sites, pre–and postimplantation loss, fetal and placental weights, grossand visceral anomalies, degree of ossification), although aslight but significant increase in litters with fetuses displayingasymmetric sternebra(e) was observed after treatment with thehighest dose of 9 mg/m³. Although the relevance of an increaseof this minor anomaly in doses which cause toxic effects indams (reduced food consumption, increased lung weights) is limitedand the number observed is within the limits of biological variability,a substance-induced effect in the high-dose group cannot beexcluded with certainty. Consequently, a no embryotoxic effectlevel of 3 mg/m³ was determined.     

A Comparison of Quality-of-Life in Patients with Dual Chamber Pacemakers and Individually Programmed Atrioventricular Delays

Dual chamber pacemakers are increasingly implanted to achieve optimal hemodynamics by AV synchrony, but the effect of AV delay programming on the patient's quality-of-life has been less well studied. The influence of an individually programmed AV delay between 100 and 250 ms on quality-of-life was investigated in a randomized, double-blind crossover study of 13 patients (69 ± 10 years of age) with dual chamber pacemakers implanted because of high degree AV block. During radionuclide ventriculography at rest, the "optimal AV delay" with the maximal left ventricular ejection fraction and the "most unfavorable AV delay" with the least ejection fraction were determined. The ejection fraction at rest with the "optimal AV delay" was 51%± 10%, and with the "most unfavorable AV delay," 44%± 11% (P < 0.0001). The optimal AV delay determined by radionuclide ventriculography correlated well with the optimal AV delay determined by Doppler echocardiography using flow velocity integrals (r = 0.78, P < 0.0016). Each patient was assigned in random order to either AV delay during a 2-week period and then the pacing mode was switched for another 2-week period. At the end of each period, patients were assessed by a functional status questionnaire to assess physical capability and two further questionnaires to quantify cardiovascular symptoms or self-perceived health. There were no differences in the two AV delays regarding the patient's perceived physical capability and specific symptoms. The patient's total judgment was identical to the optimal AV delay (score 36%± 19%) and the most unfavorable AV delay (33%± 21%). Thus, in patients with a dual chamber pacemaker, an individually programmed AV delay affects left ventricular function at rest, but has no influence on quality-of-life. The determination of the flow velocity integral by Doppler echocardiography is a simple and reliable method to optimize the AV delay if necessary.     

Chemotaxis of Gametes: A Diffusion Approximation

Sexual attraction of male gametes toward females of many brownalgae species is induced by diffusible pheromones, which leadto a chemotactic modification of the loop-like 2-dimensionalswimming paths of the males. We propose a stochastic model andanalyse a suitable diffusion approximation in order to calculatequantities as the aggregation factor, the rotational flux component,and the mean mating time.