Complexation of ß-cyclodextrin with dual molecular probes bearing fluorescent and paramagnetic moieties linked by short polyether chains.

Electron paramagnetic resonance (EPR) and fluorescence spectroscopies provide molecular-level insights on the interaction of paramagnetic and fluorescent species with the microenvironment. A series of dual molecular probes bearing fluorescent and paramagnetic moieties linked by flexible short polyether chains have been synthesized. These new molecular probes open the possibility to investigate various multi-component systems such as host-guest systems, polymeric micelles, gels and protein solutions by using EPR and fluorescence spectroscopies concertedly. The EPR and fluorescence spectra of these compounds show that the dependence of the rotational correlation time and fluorescence quantum yield on the chain length of the linker is not linear, due to the flexibility of the polyether linker. The quenching effect of the nitroxide moiety on the fluorescence intensity of the pyrene group varies with the linker length and flexibility. The interaction of these dual molecular probes with ß-cyclodextrin, in solution and in polymeric gels, was evaluated and demonstrated by analysis of EPR and fluorescence spectra.

Initial clinical trial of a closed loop, fully automatic intra-aortic balloon pump.

A new generation, closed loop, fully automatic intraaortic balloon pump (CL-IABP) system continuously optimizes diastolic augmentation by adjusting balloon pump parameters beat by beat without operator intervention. In dogs in sinus rhythm and with experimentally induced arrhythmias, the new CL-IABP system provided safe, effective augmentation. To investigate the system's suitability for clinical use, 10 patients meeting standard indications for IABP were studied. The patients were pumped by the fully automatic IABP system for an average of 20 hr (range, 1-48 hr). At start-up, the system optimized pumping parameters within 7-20 sec. Evaluation of 186 recordings made at hourly intervals showed that inflation began within 20 msec of the dicrotic notch 99% of the time. In 100% of the recordings, deflation straddled the first half of ventricular ejection. Peak pressure across the balloon membrane averaged 55 mmHg and, in no case, exceeded 100 mmHg. Examination of the data showed that as soon as the system was actuated it provided consistently beneficial diastolic augmentation without any further operator intervention. Eight patients improved and two died (one of irreversible cardiogenic shock and one of ischemic cardiomyopathy). No complications were attributable to the investigational aspects of the system. A fully automated IABP is feasible in the clinical setting, and it may have advantages relative to current generation IABP systems.

Mexiletine. Long-term efficacy and side effects in patients with chronic drug-resistant potentially lethal ventricular arrhythmias.

The antiarrhythmic efficacy of mexiletine hydrochloride (Mexitil) was evaluated in 100 patients with potentially lethal and drug-resistant ventricular arrhythmia. The efficacy of arrhythmia suppression was assessed by Holter monitoring. The overall arrhythmia suppression of ventricular premature contractions of 70% and greater was low and seen in only 22% of patients, with an additional 16% responding to a combination of mexiletine and an additional antiarrhythmic drug. The suppression of high-grade forms, couplets of 90% and greater, and complete abolition of nonsustained runs of ventricular tachycardia was achieved in 22% of patients, with 9% responding to the addition of another antiarrhythmic agent. Ventricular premature contractions, couplets, and nonsustained ventricular tachycardia were suppressed in only 16% of the cohort. The drug was poorly tolerated, with intolerable side effects developing in 49% of patients receiving mexiletine alone and in 57% of patients receiving a combination of antiarrhythmic agents. Tolerable adverse effects were relatively common but transient and dose related.

Long-term efficacy, safety and survival of patients with potentially lethal ventricular arrhythmias treated with low-dose amiodarone.

The effect of low-dose amiodarone was prospectively evaluated in 110 patients with potentially lethal ventricular arrhythmias and structural heart disease. The patient population had frequent and high-grade ventricular premature complexes (VPCs) (greater than or equal to 39/h) (multifocal, couplets, nonsustained ventricular tachycardia) refractory to conventional antiarrhythmic drugs. All patients had structural heart disease (coronary artery disease in 61%) and also a decreased left ventricular ejection fraction (LVEF) (43 +/- 16%). Patients were treated with low-dose amiodarone (maintenance dose of 275 +/- 102 mg/day.) During follow-up over a period of 15 +/- 11.5 months, 24 patients died of cardiac cause and, of these, 13 died of sudden death. Ventricular arrhythmia suppression at 1, 2, 3, and 4 years was 69%, 80%, 78%, 92% for VPCs, respectively; 96%, 90%, 92%, and 98% for couplets, respectively, and 57%, 57%, 97%, and 91% for nonsustained VTs (NVTs), respectively. Intolerable, reversible side effects requiring withdrawal were encountered in 24 patients (22%) (neurologic 10%, gastrointestinal 6.5%, skin 3.7%, proarrhythmic 0.9%, and cardiac 0.9%). Except for keratopathy (less than or equal to grade II) seen in all patients, the tolerable side effects were transient with dose adjustment. The study population was divided into two groups according to LVEF: Group A (LVEF greater than or equal to 40%, mean 54.4 +/- 9.7) and Group B (LVEF less than 40% mean, 27.7 +/- 7.2). The patients were further classified into responders (suppression of at least 70% of VPCs, 90% of couplets, and 100% of NVTs) and nonresponders. The difference in survival between responders and nonresponders in groups A and B was not statistically significant. Cumulative survival at 1, 2, 3, and 4 years was 90%, 85%, 85%, and 85%, respectively. In conclusion, low-dose amiodarone treatment: 1) Is effective in controlling VPCs and its complex forms and maintains long-term arrhythmia suppression. 2) The side effect profile compares favorably with conventional antiarrhythmics; severe side effects associated with high dosages (pulmonary, hepatic, neurologic, etc.) were rare or absent. 3) Amiodarone improves survival of patients with potentially lethal ventricular arrhythmias.

[Presence of C-reactive protein in the development of acute mumps infection. Preliminary report]. / Observations sur la présence de la protéine C réactive durant l'évolution de l'infection ourlienne aiguë. Rapport préliminaire.

Investigations conducted on subjects with epidemic parotitis serologically confirmed (hemagglutination inhibition) allowed the detection of amounts of C reactive protein (Crp) higher than the normal level in 34% of the serum samples collected during the first twelve days of illness. After that, the Crp gradually decreased. The results showed that Crp is present in more than 40% of the subjects with uncomplicated mumps and in 55 to 75% of the cases with such complications as meningitis or orchitis. In most of the subjects, the Crp was found only in the first sample, but not in the second. Nevertheless, high amounts were found later, simultaneously with anti-mumps antibodies.

[Clinical pathology of the Waterhouse-Friderichsen syndrome (author's transl)]. / Zur klinischen Pathologie des Waterhouse-Friderichsen-Syndroms

24 patients (among 35 clinical cases) with meningococcal Waterhouse-Friderichsen syndrome were submitted to pathologic anatomical examinations (including 18 microscopic investigations). Two aspects were found: 12 cases of mild suprarenal hemorrhage (histological evidence only), but associated with massive degeneration of the adrenocortical cells, leptomeningitis, distinct thymic hypertrophy with microthrombi in various organs. The other 12 cases presented massive bilateral suprarenal hemorrhage with medium status thymo-lymphaticus and distinct capillary thromboses in all organs investigated (consumptive coagulopathy).