Clinical phase I study of T-2588

A clinical phase I study for T-2588 was carried out in 25 healthy male volunteers. Each volunteer received T-2588 in one of the following doses: 100 mg capsule or tablet as a single oral administration in fasting or non-fasting state, 200 or 400 mg capsule as a single oral administration in non-fasting state or 300 or 600 mg daily for 14 approximately 15 days as a repeated administration in non-fasting state. The results are summarized below. No subjective or objective adverse effects were noted after a single oral administration. But repeated dose of 300 mg daily for 15 days and 600 mg daily for 14 days brought about abdominal distension in 1 case and soft stool in 1 case, respectively. As an abnormal change in clinical laboratory findings, 1 case with slight increase in transaminase after a single administration and 3 cases with slight increases in transaminase after repeated doses were observed. Time to reach a maximum concentration of T-2525 in blood (Tmax) was longer in subjects at non-fasting states than subjects in fasting states. Maximum blood concentration was lower in the latter than in the former. Urinary excretion rate in 8 hours after an oral administration was 19 approximately 28% and it was higher in non-fasting subject than in fasting subject. No accumulation of T-2588 was noted after repeated doses.     

A case report of inflammatory breast cancer effectively treated with cis-platinum

A 50-year-old woman with bilateral inflammatory breast cancer (T4, N1b, M1, Stage IV) underwent right extended radical mastectomy and left modified radical mastectomy following pre-operative administration of carcinostatics (ADM, 5-FU) and irradiation. However, tumor recurrence was observed at the skin and right pleural cavity after the operation. Adriamycin-containing combination chemotherapy and radiation therapy were performed, but no significant response was obtained. CDDP was then administered intravenously at a daily dose of 62.5 mg/m2 at intervals of 60 days. The pleural effusion disappeared and the extent of skin metastasis was reduced, resulting in partial response which lasted for 90 days. The serum CEA level decreased from 13.1 ng/ml to 2.3 ng/ml. As the side effects of this therapy, slight nausea, vomiting and general fatigue were observed. This result suggested that CDDP is an effective drug for inflammatory breast cancer.     

4-Aminopyridine affects synaptosomal protein phosphorylation in rat hippocampal slices

Rat brain hippocampal slices were incubated with or without the convulsant 4-aminopyridine (4-AP). From these slices a crude mitochondrial/synaptosomal membrane fraction was prepared and analyzed for endogenous protein phosphorylation. 4-AP (10(-5) M) stimulated the phosphorylation of a 50 kDa protein by 86%. The phosphorylation of this 50 kDa protein is Ca2+/calmodulin-dependent and we suggest that this protein is the lower molecular weight subunit of Ca2+/calmodulin-dependent protein kinase II (CaMK II).     

An examination of role identification by students in health education and health services administration

This research was designed to test the extent to which health education and health services administration students' perceptions of their roles as professionals matched the expectations of professional faculty. These perceptions were found to match in general. However, doubt was cast on the extent to which internships or practicums contributed to this result, since there was no change in student responses between the beginning of the junior year and end of the senior year, a period which includes fieldwork and most of the professional coursework presumed to influence professional development. Additional research is required to test this result with other student populations in other health professions and identify the point at which professional role and task definitions are amenable to change.     

Operations on the saccus endolymphaticus and vestibular nerve: have they fulfilled their promise?

The rationale for operations on the saccus and vestibular nerve in patients incapacitated by Meniere's disease as a replacement for total labyrinthectomy, has been the expectancy that less radical procedures will protect these patients from total auditory incapacity. Aware of postoperative hearing losses in some patients after 3 years, we have studied the results in 21 Shambaugh saccus decompression (SD) and 29 middle fossa vestibular nerve section (VNS) operations, in order to assess the claims made for these procedures. We found that while control of vertigo was similar to that reported elsewhere, worse hearing (AAOO criteria) developed in many cases. With SD this increased from 14% at 1 year to 58% at 10 years, and with VNS it increased from 17% at 1 year to 48% at 10 years, when the worse preoperative audiogram was used. Only 17% of SD and 11% VNS ears with serviceable best preoperative hearing had retained this at 10 years. Nineteen percent developed audiometric evidence of contralateral disease during the first 10 postoperative years. It is concluded that although, regrettably, neither of these surgical therapies appears to have the capability of preventing the progress of hearing loss, the reality of bilateral disease justifies the continued use of SD or VNS by adequately trained surgeons.     

Nurse practitioner and physician assistant practices in three HMOs: implications for future US health manpower needs.

This study empirically examines the practices of non-physician providers (NPPs) within three large competitive health maintenance organizations (HMOs), as well as the physicians' and NPPs' views regarding the ideal role of NPPs. These roles are compared with NPP delegation patterns incorporated in the modeling methodology developed by the Graduate Medical Education National Advisory Committee (GMENAC). GMENAC recommended relatively high levels of delegation by physicians to NPPs. One of the HMO sites made use of NPPs at rates even higher than GMENAC's national ideals, while the rates at the other two were lower. The normative ideals for pediatric NPPs developed at each HMO were consistently higher than their actual roles. Concerns with acceptance and the role of NPPs are clearly no longer issues. Instead, the limits on NPP involvement appear to relate to considerations of costs, availability, and the increasing numbers of physicians competing for similar opportunities.     

Investigation of basic imaging properties in digital radiography. 8. Detection of simulated low-contrast objects in digital subtraction angiographic images

We investigated the effects of imaging and display conditions on the detectability of low-contrast objects in digital subtraction angiographic (DSA) images. The test images were produced by superimposition of low-contrast objects on a uniform noisy background obtained with a DSA system. We employed 18-alternative forced-choice (18-AFC) experiments and predictions based on statistical decision theory to study the dependence of the threshold contrasts of the test objects on the object size, incident x-ray exposure, display window width, and display medium. The results indicated that the threshold contrast decreased with increasing object size, and that the detectability of an object of a given size increased with increasing incident x-ray exposure and decreasing width of the display window. We found that the signal-to-noise ratio (SNR) obtained from the perceived statistical decision theory model, which includes the observer's internal noise, can accurately predict the detectability of low-contrast objects in DSA images. The threshold SNR corresponding to 50% correct detection in the 18-AFC experiments had a constant value of 3.8, in agreement with results reported previously for screen-film systems. The theoretical model will be useful for prediction of the performance of a DSA system based on its physical characteristics, and for evaluation of the tradeoff between patient exposure and diagnostic accuracy for a given DSA unit.     

Actions of phencyclidine on the action potential and membrane currents of single guinea-pig myocytes

The direct actions of phencyclidine (PCP) on mammalian sarcolemma were examined by determination of the drug's effects on the action potentials of isolated guinea-pig ventricular cells, and on the underlying ionic currents. PCP (10(-6) to 10(-4) M) did not alter the resting membrane potential but produced a dose-dependent prolongation of the duration of the action potential, and a reduction of the rate of depolarization of phase 0 (Vmax) of the action potential. Voltage clamp experiments revealed that PCP blocks both myocardial Ca++ channels and myocardial time-dependent K+ channels. The K+ channel blockade was shown to exhibit an apparent voltage-dependence. The effects of PCP on these ionic channels could explain previous reports of it prolonging myocardial action potentials and conflicting reports of positive and negative inotropism.