Ritanserin in the treatment of alcohol dependence – a multi-center clinical trial

Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT₂ receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint, there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related prolongation of subjects’ QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important role for ritanserin in the treatment of alcohol dependence. Received: 30 April 1996/Final version: 3 July 1996     

Studies on Propafenone-type Modulators of Multidrug-Resistance IV: Synthesis and Pharmacological Activity of 5-Hydroxy and 5-Benzyloxy Derivatives

A series of 5-hydroxy and 5-benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR-modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol 3 . Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds 5a–d . Subsequent cleavage of the benzyl group gave the 5-hydroxy analogs 6a–d . Structure activity relationship studies showed, that the 5-hydroxy derivates 6a–d fit the log P/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5-benzyloxy analogs 5a–d showed almost identical EC₅₀ values, independent of their log P value.     

Recurrent dislocation of the patella and the Goldthwait operation

In this study 17 patients with recurrent dislocation of the patella were followed up 10 years after their Goldthwait operation. The subjective and clinical findings were excellent or good in 70%. X-radiographs indicated osteoarthritis of the femoropatellar joint in 60%. Concerning the aetiopathological factors, we found an increased external torsion of the afflicted extremity (measured by computed tomography).     

A Comparison Between Recipients Receiving Matched Kidney and Those Receiving Mismatched Kidney from the Same Cadaver Donor

The optimal allocation of cadaveric kidneys for transplantation with reference to human leukocyte antigen (HLA) match and sharing these organs to a distant center remains controversial. The current analysis was performed using the United Network for Organ Sharing (UNOS) database for cadaveric kidney transplants (Tx) between 1988 and 1997. The graft survivals of zero-mismatch (matched) kidneys with the mate (mismatched) kidneys were compared. There were 2385 donors and 4770 Tx. Significant differences in recipient demographics between matched and mismatched Tx were: fewer African-American race (AA) in the matched group (9.0% vs. 21.9%), higher number of previous Tx (25.5% vs. 14.8%) and elevated mean cold ischemia time (24.0 vs. 22.2 h). Post-Tx dialysis requirements were similar (22.8% vs. 24.1%, p = 0.62) and matched kidneys had to travel more distance (920 vs. 232 miles). Using a Cox model, the matched group had a decreased relative hazard of graft failure of 23.0% (p = 0.0002) or 35% (p < 0.0001) with and without censoring for death. There was significantly better graft survival in the matched recipients in all pairs except AA (matched) and non-AA (mismatched). For older donors (> or = 50 years, n = 1508), the matched grafts survival was marginally significant (p =0.05). Matched kidneys have improved survival compared with the mismatched kidneys despite the longer distance traveled. The benefit of mismatched transplants was predominantly seen in non-AA.     

Additional myocardial salvage by coadministration of the epoprostenol analog taprostene to recombinant single-chain urokinase-type plasminogen activator in a canine coronary thrombosis model

In open chest dogs myocardial ischemia was induced by formation of an occlusive thrombus in the left anterior circumflex artery (LCX). Reperfusion of the LCX was achieved by infusion of the fibrin specific recombinant single-chain urokinase-type plasminogen activator (r-scu-PA). The myocardial salvage by r-scu-PA alone and in combination with the epoprostenol (prostacyclin) analog taprostene (CG 4203) was compared. There were four experimental groups: group 1 (n = 4) did not receive any treatment after LCX thrombosis; in group 2 (n = 9) at 100 min after LCX thrombosis r-scu-PA (20 micrograms.kg-1.min-1 i.v. for 30 min) was infused; in groups 3 and 4 treatment with taprostene started concomitantly with r-scu-PA infusion. The taprostene infusions lasted for 120 min and the doses were 0.1 microgram.kg-1.min-1 in group 3 (n = 6) and 0.215 microgram.kg-1.min-1 in group 4 (n = 6). Time to r-scu-PA-induced recanalisation ranged from 18-22 min with no significant difference between groups 2-4. Percent of left ventricle at risk did not differ between the groups. Infarct size as percent of the risk zone was 48.3 +/- 7.7 in group 1, 25.3 +/- 3.7 in group 2, 21.3 +/- 6.5 in group 3 and 17.1 +/- 3.5 in group 4 (p less than 0.05 groups 2-4 vs group 1). Incidence of ectopic beats increased after r-scu-PA-induced reperfusion in groups 2-4, but was significantly reduced by taprostene.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitative immunocytology as a marker for indications and follow-up of recurrence prevention of superficial urinary bladder cancers

In 1985, we initiated a prospective clinical trial to evaluate the risk of recurrence for superficial bladder cancer. Up to now, 41 patients subjected to TUR have subsequently been monitored by immunocytology with a monoclonal antibody (mab 486 p) recently developed in our laboratory. Of these patients, 15 (36.6%) remained marker-negative and received no prophylactic therapy. There was only one recurrence (6.7%) in this subset of patients, whereas 10 out of 26 (38.5%) marker-positive patients have so far developed recurrent malignancies. In all cases, the conversion of immunocytological characteristics preceded visible recurrence by 2-5 months. These preliminary results indicate that immunocytology might make it possible to identify patients at low risk of recurrence more accurately than has so far been feasible with standard cytology or flow-cytometry.     

Distance learning in a school nurse credential program.

Distance learning, which encompasses many methodologies, is becoming a more readily available educational alternative. Because there are a limited number of school nurse credential programs and the demand for school nurses is increasing, distance learning may be a viable method of instruction. This article describes the authors' experiences organizing and presenting distance learning courses to five remote sites for students in a university school nurse credential program. After numerous inquiries, potential students from several areas were surveyed, and arrangements were made with universities in those areas to receive two-way audio and video transmissions of two seminar courses; later, two clinically oriented courses in the school nurse program. Students were able to complete their program requirements by taking equivalent course work at their local universities. Perceptions of students and the instructor, course evaluation, and practical suggestions are shared. Guidelines for potential students about selecting quality distance education programs are also noted.     

Prophylactic nasal continuous positive airway pressure after major vascular surgery: results of a prospective randomized trial

BACKGROUND: The efficacy of nasal continuous positive airway pressure (nCPAP) as a prophylactic method for preventing cardiopulmonary complications after major vascular surgery has not been investigated. PATIENTS/METHODS: In a prospective randomized trial, 204 patients undergoing elective midline laparotomy for vascular surgery were randomized to receive standard therapy ( n=105) or additional prophylactic nCPAP ( n=99) for the first postoperative night. Postoperative oxygenation, incidence of severe cardiac, and pulmonary complications, length of intensive care surveillance and length of total postoperative hospital stay (LOS) were compared. RESULTS: Prophylactic nCPAP significantly reduced the number of patients with severe oxygenation disturbances defined as paO(2) < 70 mmHg with FiO(2) > or = 0.7 (5 versus 17, P=.01). There were no differences with respect to death, cardiac and pulmonary complications, length of intensive care surveillance or LOS. CONCLUSION: Prophylactic 12 h nCPAP significantly reduces the occurrence of postoperative oxygenation disturbances but has no effect on cardiac or pulmonary complications, need for intensive care, LOS or mortality after major vascular surgery.