Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182     

Hemodynamic responses to alfentanil in halothane-anesthetized dogs

Alfentanil is an opioid that has been used both as a sole anesthetic and in conjunction with other inhalation anesthetics. However, its effects on myocardial performance and regional blood flow are not clearly known. Using sonomicrometry and radioactive microsphere techniques, we examined the hemodynamic responses to alfentanil when given as a loading dose (45 micrograms/kg) followed by continuous infusion (3 micrograms X kg-1 X min-1) in dogs anesthetized with halothane. Similar plasma levels of alfentanil were observed after the loading and infusion doses, and both techniques of administration produced a significant reduction in arterial pressure without change in global or regional function of the left ventricle. Although cardiac output and left ventricular end-diastolic pressure remained unchanged, heart rate and systemic vascular resistance decreased significantly after the loading dose and recovered slightly when alfentanil was infused continuously. Despite the systemic hypotension, alfentanil did not alter perfusion to the heart, brain, muscle, and skin; however, blood flow to the renal cortex and the arterial supply to the liver decreased by 25 and 60%, respectively. Reduction in blood flow to the kidneys and the liver suggests that alfentanil should be used with caution when normal function of these organs is in question.     

Usher syndrome: clinical findings and gene localization studies

The issue of genetic heterogeneity is a critical problem in the localization of the gene(s) for Usher syndrome. Based on the data obtained on families studied to date, the differences between type I and type II Usher syndrome appear quite distinct with regard to auditory and vestibular function. Although the majority of families can be confidently diagnosed as typical type I or type II, clinical investigations revealed four families with findings that did not fit into either of the two more common subtypes. These findings emphasize the critical importance of an in-depth clinical analysis concomitant with the linkage investigation to assure accurate subtyping of Usher syndrome. Based on an analysis of only those families with definite type I or type II Usher syndrome, approximately 17% of the genome can be excluded as a potential site of the gene for type I, and 14% can be excluded as the site for the type II gene. This study will continue until the Usher gene(s) is successfully localized.     

Digital imaging with a photostimulable phosphor in the chest of newborns

To evaluate use of a digital photostimulable phosphor imaging system in the neonatal nursery, 150 newborns were divided into three groups of 50. In the first two groups, screen-film and computed radiographs of the chest were obtained at the same radiation exposure; in the third group, computed radiographs were obtained with a 50% dose reduction (half-exposure computed radiographs). All images were blindly evaluated by three readers who scored the quality of visualization of the mediastinum, lung, bone, soft tissues, and endotracheal and nasogastric tubes, and also image density. No statistical differences in visualization of tubes existed among the three groups. Visualization of the mediastinum, lung, bones, and soft tissues was statistically significantly better on computed radiographs than on half-exposure computed radiographs; visualization of the lungs, bones, and soft tissues was statistically significantly better on screen-film radiographs than half-exposure computed radiographs. Image density was statistically better on computed and half-exposure computed radiographs than on screen-film radiographs.     

Applications of biological control in resistant host-pathogen systems.

Insect pest species can have devastating effects on crops. Control of these insect pests is usually achieved by using chemical insecticides. However, there has been much cause for concern with their overuse. Consequently, research has been carried out into alternative forms of control, in particular biological control methods. Recent laboratory studies have indicated that these natural forms of control can induce resistant strains of insect pest. In this paper we present a discrete-time host-pathogen model to describe the interaction between a host (insect species) that can develop a resistant strain and a pathogen (biological control) that can be externally applied to the system. For this model we use a single-state variable for the host population. We show that the proportion of resistance in the population impacts on the viability of the host population. Moreover, when the host population does persist, we explore the interaction between host susceptibility and host population levels. The different scenarios which arise are explained ecologically in terms of trade-offs in intrinsic growth rates, disease susceptibility and intraspecific host competition for the resistant subclass.