Clinical Experience with the Elema Vario Pacemaker

Early problems after implantation of an endocardial electrode for permanent pacing occur in many patients. Difficulties can be anticipated in many of these patients and their management made much easier by a knowledge of the daily endocardial threshold obtained in patients with an implanted Elema Verio pacing unit by a simple non-invasive technique using a magnet and electrocardiogram. Twenty patients are described in whom permanent pacing with an Elema Vario unit was undertaken. The practical advantages of this unit can be readily seen in the patient who developes exit block or in the patient with obstructive airways disease, in whom frequent coughing or right ventricular hypertrophy may make stable electrode placement difficult. The chief advantage of the Elema Vario pacemaker is the extreme simplicity with which knowledge of the endocardial threshold can be obtained.     

Clinical Laboratory Experience with the Improved Enterotube

The reactions elicited in this evaluation of the improved Enterotube indicate the efficacy of using this device for the differentiation of the members of the family Enterobacteriaceae.     

Preclinical and Clinical Experience with Liposome-Encapsulated Mitoxantrone

Abstract

Mitoxantrone (MTO) was encapsulated by different preparation techniques into liposomes of different lipid compositions. MTO complexed to liposomes containing phosphatidic acid (PA, PA/MTO-liposomes) had blood pharmacokinetics which were comparable to the free drug. Accumulation in liver and spleen was significantly higher with PA/MTO-liposomes. Acute toxicity was 2.5 fold lower and the liposomal preparation had better antitumor effects in the L1210 leukemia and in a large cell lung cancer model. In a phase I study in patients with advanced breast cancer the maximal tolerable dose of PA/MTO-liposomes was 18 mg/m². The PA/MTO-liposomes were well tolerated, granulocytopenia was the dose-limiting effect. Clinical responses were seen in soft-tissues, liver and bone metastases. The properties of new liposome formulations with MTO were evaluated MTO-liposomes prepared by the pH-gradient loading method and modified with polyethylene glycol(2000)-diphosphatidylethanolamine (PEG(2000)-DPPE) had pharmacokinetic properties which were significantly superior to the PAJMTO-liposomes. Compared to free MTO and PA/MTO-liposomes, ΔpH MTO-liposomes containing PEG(2000)-DPPE, prepared with a ΔpH of 5 across the liposome membrane produced a 40-fold increase of the area under the curve (AUC). The new MTO-liposome formulations have excellent antitumor activities in the LI210 leukemia model. These results and further preclinical evaluation of the ΔpH MTO-liposomes support the initiation of a phase I study.     

Clinical Experience with the Dalkon Shield Intrauterine Device

Preliminary acceptability and reliability tests of the Dalkon Shield were done in 377 women over 17 months, amounting to 3,028 months of use. There was a 98% follow-up. The pregnancy rate of 4·7 and expulsion rate of 6·3 do not meet the claims described in initial trials by the developers of the device. Nevertheless, the Dalkon Shield seems to be an advance in intrauterine contraception since it has the advantages of a lower expulsion rate than the “first generation” inert intrauterine devices.     

Preclinical and Clinical Experience with a Doxorubicin-Liposome Preparation

Abstract

Entrapment of doxorubicin in liposomes results in increased drug concentrations in liver and spleen and decreased uptake by the heart muscle. these pharmacologic changes can be exploited to reduce the drug's toxicity and increase its therapeutic index in selected neoplastic conditions. We review here our preclinical and phase I clinical data with liposome-associated doxorubicin. these studies, together with preliminary observations on the pharmacokinetics of the liposome-associated drug and on the imaging of radiolabeled vesicles in patients, suggest that the maximal tolerated dosage is significantly increased over that of the free drug and that the reticuloendothelial system is responsible for the rapid and dominant pathway of liposome clearance. the implications of various pharmacologic aspects of liposome behavior in the circulation are also discussed.