Phase II trial of 10 deaza-aminopterin in patients with bladder cancer

Summary Deaza-aminopterin is a folate analog which is transported more rapidly than methotrexate into cells and appears to be more active than methotrexate against human and animal tumor in vitro. Fifteen patients with advanced urothelial tract cancer were given deaza-aminopterin 30–37.5 mg/m² IV QW. In responding patients drug was given QOW after 4–6 consecutive doses. Doses were escalated or de-escalated by 7.5 mg/m² depending on toxicity. Twelve patients had received prior chemotherapy which included methotrexate in nine. Three patients achieved a partial remission lasting 1, 3, and 3 months respectively: all responders had previously failed methotrexate after an initial response to a methotrexate containing regimen. None of the six patients who were methotrexate naive responded to deaza-aminopterin; 3 subsequently received methotrexate without response. Mild mucositis was universal and in 5 was severe. Six patients had an increase in liver transaminases probably secondary to anti-folate hepatotoxicity. Other toxicities included diarrhea, nausea, skin rash and fever. Further studies are needed to define the precise efficacy of deaza-aminopterin in patients with urothelial tract cancers.     

Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease.

The long-held belief that degeneration of the cholinergic basal forebrain was central to Alzheimer's disease (AD) pathogenesis and occurred early in the disease process has been questioned recently. In this regard, changes in some cholinergic basal forebrain (CBF) markers (e.g. the high affinity trkA receptor) but not others (e.g., cortical choline acetyltransferase [ChAT] activity, the number of ChAT and vesicular acetylcholine transporter-immunoreactive neurons) suggest specific phenotypic changes, but not frank neuronal degeneration, early in the disease process. The present study examined the expression of the low affinity p75 neurotrophin receptor (p75(NTR)), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well-characterized individuals who have been classified as having no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild AD. Relative to NCI individuals, a significant and similar reduction in the number of nucleus basalis p75(NTR)-immunoreactive neurons was seen in individuals with MCI (38%) and mild AD (43%). The number of p75(NTR)-immunoreactive nucleus basalis neurons was significantly correlated with performance on the Mini-Mental State Exam, a Global Cognitive Test score, as well as some individual tests of working memory and attention. These data, together with previous reports, support the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline. Although there was no difference in p75(NTR) CBF cell reduction between MCI and AD, it remains to be determined whether these findings lend support to the hypothesis that MCI is a prodromal stage of AD.     

Inclusion cyst of the tunica albuginea: Demonstration by ultrasound

A 35-year-old man discovered a 1-cm nodule at the upper pole of the left testicle after blunt focal trauma. While the pain, tenderness, and location suggested hematoma or appendiceal torsion, the demonstration by ultrasound of the size, cystic nature, and extraparenchymal location was consistent with the rarely documented cyst of the tunica albuginea.     

Training Synergies Between Medical Informatics and Health Services Research: Successes and Challenges

Stanford''s two decades of success in linking medical informatics and health services research in both training and investigational activities reflects advantageous geography and history as well as natural synergies in the two areas. Health services research and medical informatics at Stanford have long shared a quantitative, analytic orientation, along with linked administration, curriculum, and clinical activities. Both the medical informatics and the health services research curricula draw on diverse course offerings throughout the university, and both the training and research overlap in such areas as outcomes research, large database analysis, and decision analysis/decision support. The Stanford experience suggests that successful integration of programs in medical informatics and health services research requires areas of overlapping or synergistic interest and activity among the involved faculty and, hence, in time, among the students. This is enhanced by a mixture of casual and structured contact among students from both disciplines, including social interactions. The challenges to integration are how to overcome any geographic separation that may exist in a given institution; the proper management of relationships with those sub-areas of medical informatics that have less overlap with health services research; and the need to determine how best to exploit opportunities for collaboration that naturally occur.Training in medical informatics and health services research has been closely linked at Stanford University for almost two decades. Although the close linkage was deliberate, it was facilitated by historical circumstances, in particular the common academic structures in which both programs arose. In this paper, we describe some of that rationale and history, identifying the areas of overlap that we have pursued in coordinating the training opportunities for graduate students and fellows in both areas of study. As we shall note, the synergies have been great, and in some cases trainees have collaborated closely on research while also taking some of the same courses. We believe that these interactions can be a model for the design of training programs that encourage scholarly interactions between medical informatics and health services research. Although our initial charge was to describe both the successes and failures in integrating the programs, we found that we could not identify any outright failures and that it would be better to delineate the complexities and challenges that we have faced in bringing together these two disciplines.     

Use of a geographic information system to track smelter-related lead exposures in children: North Lake Macquarie, Australia, 1991–2002

Background  

To determine patterns of childhood lead exposure in a community living near a lead and zinc smelter in North Lake Macquarie, Australia between 1991 and 2002.