Clinical Outcomes Following Percutaneous Coronary Intervention With Drug‐Eluting Stents Versus Bare Metal Stents in Patients on Chronic Hemodialysis

Background

Patients on chronic hemodialysis (HD) are recognized as a high‐risk group for adverse events after percutaneous coronary intervention, and whether drug‐eluting stents (DES) are associated with improved outcomes over bare metal stents (BMS) is still uncertain. The purpose of this study was to assess the efficacy of DES compared with BMS at short‐ and long‐term follow‐up (FU) in an unselected sample of HD patients.

Methods and Results

In the time period 2005–2010, consecutive patients on chronic HD treated with percutaneous coronary intervention (PCI) and stent implantation were retrospectively selected and analyzed. A total of 169 patients were selected, 77 treated exclusively with BMS and 92 exclusively with DES. Baseline clinical characteristics were similar in the 2 groups as well as the number of treated vessels, treated lesions, and the stent per patient ratio. At longest available FU, no difference between the 2 study groups was found in terms of cardiac death (18.2% vs 16.3%, P = 0.83), myocardial infarction (2.5% vs 8.6%, P = 0.09), cerebrovascular accidents (0% vs 1.1%, P = 0.98), and target vessel revascularization (TVR) (9.1% vs 16.3%, P = 0.17). Major adverse cardiac and cerebrovascular events‐free survival at 1,500 days in the BMS and DES groups was 57.6% and 50.9% (P = 0.11), respectively.

Conclusions

PCI in patients on chronic HD treatment is associated with a high incidence of adverse events at FU, mainly represented by death. In our study, the use of DES was not associated with a reduction of target lesion revascularization (TLR) and TVR.

     

Synthesis and biological activity of carboxyl terminally extended dermorphins

Dermorphinoyl(DMR)-glycine, DMR-sarcosine and DMR-glycyl-arginine have been prepared in order to examine the effect of C-terminal extension of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH₂) on opioid activity. On GPI preparation the addition of Gly, Sar, or Gly-Arg to the carboxyl terminus of dermorphinoic acid was detrimental to μ activity: dermorphinoyl-derivatives, in fact, retain only 5–20% of dermorphin potency. Following intracerebroventricular administration (tail-flick test), whereas the analgesic activities of compounds showed the trend dermorphin >DMR-Sar> DMR-Gly-Arg>DMR-Gly>morphine, the nonapeptide displayed highest activity after subcutaneous injection in mice: DMR-Gly-Arg was 2.5 and 10 times more potent than dermorphin and morphine, respectively.     

Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation

Endothelial microparticles (EMP) released from activated or apoptotic endothelial cells (EC) are emerging as useful markers for detection of EC dysfunction. Our recent observation that EMP carry von Willebrand factor (vWf) led us to investigate their interaction with platelets. EMP were incubated with normal washed platelets in the presence or absence of ristocetin, then platelet aggregates were measured by flow cytometry. In the absence of ristocetin, negligible EMP conjugated with platelets (< 5%) but in the presence of ristocetin (1 mg mL(-1)), EMP induced up to 95% of platelets to aggregate. EMP-platelet interaction was 80% blocked by anti-CD42b, or by 0.1 microm filtration to remove EMP. Platelet aggregates induced by normal plasma or high molecular weight vWf (Humate-P) dissociated 50% within 15-25 min following 1:20 dilution. In contrast, aggregates formed with EMP persisted two- to threefold longer with the same treatment, indicating greater stability. A similar degree of prolongation of dissociation was observed using plasma from thrombotic thrombocytopenic purpura (TTP) patients compared with normal plasma. Addition of EMP to plasma from severe von Willebrand disease restored his ristocetin-induced platelet aggregation. Multimer analysis of vWf on EMP showed unusually large vWf (ULvWf). In summary, EMP carries ULvWf multimers, promote platelet aggregates, and increase the stability of the aggregates thus formed.     

Long-term Reproducibility of Response to Noninvasive Programmed Cardiac Stimulation in Spontaneous, Sustained Ventricular Tachycardia Treated with Amiodarone Therapy

A total of 73 noninvasive serial electrophysiological studies were carried out in 12 patients with spontaneous sustained ventricular tachycardia, inducible in spite of chronic treatment with amiodarone, in order to verify the effect of this drug on the long-term reproducibility of the test. A ventricular tachycardia was induced in 72 of 73 times; in 59% of cases, the clinical form was induced. In 8 of 12 patients, two or more types or morphologies of ventricular tachycardia could be induced. The induction modes (driving rate and number of extrastimuli) changed considerably in different studies. During a follow-up of 12 ± 6 months, 5 out of 12 patients had spontaneous relapses. We observed no differences between these patients and the others regarding inducibility, types and morphologies of the induced tachycardias, or induction modes. Therefore, when ventricular tachycardia is inducible in spite of chronic amiodarone therapy, it is always inducible during follow-up, even if a great intrapatient change of type and the morphology of induced tachycardias and induction modes is observed. However, since similar electrophysiological features are present in patients with and without spontaneous recurrence of ventricular tachycardia, serial electrophysiological studies are of little value in predicting the clinical outcome.     

Flow Cytometry and Sizing for Routine Andrological Analysis

Summary: Flow fluorometry and Coulter type sizing analysis of sperm have been applied separately in order to improve human semen analysis. Different methods of sample preparation were evaluated and a protocol involving prestaining pepsin treatment of sperm samples is proposed for fluorometric analysis. The data obtained with fluorometry and sizing analysis result in different kinds of information: Coulter counting allows to automate sperm counting and fluorometry yields more datailled information about normozoospermia and oligozoospermia by determining the proportion of mature spermatozoa and immature germ-cells. These two methods, together with light microscopy, may help to explore the correlation of fertility and pathology of spermatozoa. The aim of these investigations is to yield the preconditions for simultaneous two-parameter analysis of DNA content and cellular size distributions. Zusammenfassung: Durchflußcytophotometrie und Größenmessung für andrologische Routineuntersuchungen von Spermatozoen Durchflußanalyse und Größenanalyse nach dem Coulter-Prinzip wurden angewandt, um die Begutachtung menschlichen Spermas zu verbessern. Unterschiedliche Methoden der Probenaufbereitung wurden ausprobiert, und ein Protokoll mit Pepsinbehandlung der Spermatozoenproben für fluorometrische Analysen wird vorgeschlagen. Die mit der Cytofluorometrie und Größenanalyse erhaltenen Daten ergeben unterschiedliche Informationen: Das Coulter-Prinzip erlaubt die Automatisierung der Spermatozoenzählung, und die Fluorometrie ergibt detailliertere Erkenntnisse über Normozoo-spermie und Oligozoospermie, da die Unterscheidung von reifen Spermatozoen und unreifen Keimzellen ermöglicht wird. Diese beiden Methoden können in Kombination mit der Lichtmikroskopie helfen, die Korrelation zwischen Fertilität und Pathologie von Spermatozoen zu erkunden. Das Ziel dieser Untersuchungen ist es, die Voraussetzungen für gleich-zeitige Zweiparameteranalysen des DNA-Gehaltes und der zellulären Größenverteilungen zu liefern.