Synthesis and Purine P2X Receptor Antagonist Activity of Thiazole Derivatives

The ability of 12 new thiazole derivatives to influence the muscle contractility mediated by purine P2X receptors has been studied in vitro using isolated tissues of rats and guinea pigs. Most of the synthesized compounds did not cause significant effects, but two compounds exhibited pronounced antagonism with respect to P2X-mediated contractility response. These compounds offer a good starting point for the synthesis of new effective antagonists of P2 receptors. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 6, pp. 22 – 25, June, 2005.     

Okulokutane Hypopigmentierung und thrombozytäre Gerinnungsstörung

Ohne Zusammenfassung     

Pharmacotherapy of ventricular fibrillation. A prospective study in an emergency medical service

This prospective study investigated the effects of standard pharmacotherapy in out-of-hospital ventricular fibrillation (VF) after i.v. or endobronchial (e.b.) administration of epinephrine and lidocaine. METHODS. Only patients presenting with out-of-hospital VF were included in this study, whereby VF of noncardiac origin was excluded. Cardiopulmonary resuscitation (CPR) was performed according to the guidelines of the American Heart Association. Basic life support was initiated by Emergency Medical Service (EMS) technicians. The first step of advanced life support was immediate defibrillation by the EMS physician. Epinephrine was given in doses of 2.5 mg e.b. or 1.0 mg i.v. If indicated, patients received 200-500 mg lidocaine e.b. or 100 mg i.v. The course of CPR was tape-recorded and 2-3 blood samples were taken from each patient for drug monitoring. Plasma levels of epinephrine and lidocaine were measured by high-pressure liquid and gas chromatography, respectively, and then correlated to the course of CPR. RESULTS. Forty-seven patients presented VF on arrival of the EMS physician. Restoration of spontaneous circulation was achieved in 64% (Table 3), and 30% of the patients were discharged from hospital without major neurologic deficits. Immediate defibrillation before initiation of pharmacotherapy produced a success rate of 15.8%, whereas defibrillation after drug therapy was successful in 61.5% of cases. Following e.b. instillation of 2.5 mg epinephrine (Fig. 1), median peak concentrations of epinephrine (40.2, range 4.0-79.8 ng/ml) were reached after 3-4 min and plasma levels greater than or equal to 10 ng/ml were seen for 20 min. After i.v. injection of 1.0 mg epinephrine (Fig. 2) maximum concentrations (71.6, range 4.7-104.2 ng/ml) were measured after 1-2 min and plasma levels decreased below 10 ng/ml after 10 min. Following e.b. instillation of 400-500 mg lidocaine mean lidocaine concentrations within the therapeutic range (2-5 micrograms/ml) were reached after 4-5 min and remained within these limits for 20-30 min. Peak concentrations were obtained after 12 min. Doses of 200-320 mg lidocaine e.b. failed to achieve therapeutic plasma levels (Fig. 3). Regarding the pharmacodynamic aspects of drug therapy, 22.5% of the initial survivors were resuscitated from VF without therapeutic epinephrine, presenting with mean endogenous epinephrine concentrations of 7.1 ng/ml, 51.6% of patients were resuscitated after epinephrine therapy with plasma concentrations greater than 20 ng/ml. In only 1 case could a relationship be demonstrated between the administration of lidocaine and resuscitation success. CONCLUSION. In CPR, the e.b. administration of epinephrine and lidocaine is a reliable alternative to the i.v. injection route of these drugs. Recommended doses are 2.5 mg for epinephrine and 400-500 mg for lidocaine. Resuscitation from VF requires immediate epinephrine therapy if initial defibrillation is not successful. Lidocaine has no effect on resuscitation from VF and therefore should be used specifically for antiarrhythmic therapy after restoration of spontaneous circulation.     

Phase II study of iproplatin in metastatic breast carcinoma

Thirty patients with progressive metastatic breast cancer and one prior chemotherapy regimen were treated with iproplatin at a starting dose of 300 mg/m2 iv every 3 weeks. After the first 11 patients, the starting dose was decreased to 270 mg/m2. There were one complete remission, three partial remissions, and two minor responses. Responses were observed in soft tissue and osseous and visceral areas. Grade 3 nausea and vomiting were observed in 38% of patients, and grade 3 diarrhea occurred in 31%. The dose-limiting toxicity was thrombocytopenia, which required dose de-escalation in 15 patients. No nephrotoxicity, neurotoxicity, or ototoxicity was observed. Iproplatin has modest antitumor activity in this group of previously treated patients with metastatic breast cancer.     

Intra-articular arteriovenous malformation of the knee

Two young men with longstanding suprapatellar masses are presented. The initial clinical diagnosis was of a synovial or soft tissue tumour. Magnetic resonance imaging showed the features of an arteriovenous malformation (AVM). Surgical exploration and biopsy confirmed the diagnosis. AVMs, although rare, should be considered as a possible diagnosis of a peri-articular swelling of the knee.     

Effect of dithranol therapy on membrane, basement membrane and nuclear markers in psoriasis lesions

We investigated the effects of anti-psoriatic therapy with dithranol (1/20-1%) in salicylic acid (0.5%) in white petrolatum on lesional skin. FITC-labeled lectins and pemphigus vulgaris antibodies (PV) served as analytical means to study the glycocalyx. Antibodies of bullous pemphigoid (BP) were used as basal membrane markers. Nuclear antigens were recorded according to the binding of speckled, anti-nuclear antibodies (ANA) as well as antibodies to dsDNA. With some lectins, dithranol therapy resulted in pronounced fluorescence of the lower parts of the basal cells. ConA was fixed by the basal cell layer. To a lesser degree, ANA were fixed by nuclei of keratinocytes. PV antibodies were not fixed at all.     

Liver operations in Sweden in 1987-99.

BACKGROUND AND AIMS: Liver surgery is developing with new techniques and treatment modalities. The aim of this study is to describe liver surgery over a long period of time in a country with a public health care system. PATIENTS AND METHOD: A register study including adult patients admitted for liver resection in Sweden (population 8.8 million) selected from the Inpatient Register 1987-99. Additional data were collected from the Swedish Cancer Register and the Cause of Death Register. Analyses of the patients, indications, mortality and causes of death are presented. RESULTS: 2,405 operations were performed (21 per million per year). The most frequent indication was colorectal metastases (27%). The 5-year survival after an operation for primary liver cancer and colorectal liver metastases was 27% and 26%, respectively. CONCLUSIONS: Few patients were admitted for liver operations compared to expected figures. The survival rates are in conformity with those previously published. With an increasing awareness of the relatively favourable prognosis and the introduction of new methods, the volume of liver operations will probably increase in Sweden.