Richard A. Harris

Acute Neurologic Dysfunction Associated with High-Dose Chemotherapy and Autologous Bone Marrow Rescue for Primary Malignant Brain Tumors

UNLABELLED Acute neurologic complications occurred 103 times in 50 (54%) of 92 patients (primarily children) treated with high-dose chemotherapy and autologous bone marrow rescue for primary central nervous tumors. Different types of neurologic compromise occurred during the chemotherapy infusion as compared to the first 100 days after the chemotherapy and the greater-than-100-day time period. The causes of the neurologic compromise were also time sensitive. BACKGROUND Results of treatment for children with primary brain tumors using high-dose chemotherapy with autologous marrow rescue (ABMR) have been encouraging. However, the neurotoxicity associated with this technique remains a major concern. We reviewed the records of 92 patients who underwent ABMR for malignant brain tumors between 1986 and 1992 for the occurrence and timing of acute neurologic dysfunction (AND). METHODS Individual investigators at the participating institutions retrospectively completed standardized forms on each patient. The manner in which the distribution of AND versus time of treatment emerged led to the establishment of distinct time periods for data analysis and discussion. The pre-ABMR period included those events that occurred during the chemotherapy infusion, the early posttreatment period included the first 100 days following bone marrow rescue, and the late posttreatment period was greater than 100 days following bone marrow rescue. RESULTS Fifty patients (54%) had 103 episodes of AND. AND included encephalopathies with or without hallucinations or coma (32), seizures (23), headaches (9), ataxia-tremor-dysarthria syndrome (7), anorexia and nausea syndrome (7) and others (25). During the chemotherapy infusion, encephalopathies and seizures were most common. Hallucinations occurred primarily related to drug infusion, while encephalopathies without hallucinations were usually due to demonstrable dysmetabolic states. In the 100 days following ABMR, dysmetabolic states and iatrogenic factors caused 45% and progressive disease caused 33% of AND. Greater than 100 days from ABMR, progressive disease caused 55% of AND; 7 patients were noted to develop chronic anorexia and nausea of unclear etiology. The occurrence of neurologic compromise was not related to the chemotherapy regimens, tumor histology, tumor location, patient age, prior treatment, or the amount of tumor at time of treatment. Dexamethasone use was the only clinical factor associated with AND (p < 0.004). CONCLUSIONS The cause of AND was definable for 95% of instances that occurred within 100 days of ABMR. Early AND was often iatrogenic and reversible. The greater the time from ABMR the more likely AND was due to progressive disease. Clinical factors could not predict the occurrence of AND as only the concurrent use of dexamethasone at the time of treatment proved significant. Although frequent, AND should not be considered a limiting toxicity of this approach or preclude the use of this technique.

Let’s Stop Educating Closet Historians

Abstract Public administration is inherently an interdisciplinary field, prominently incorporating theory and methods from economics, political science, and sociology. Less obviously, however, MPA curricula include historical treatments of particular policy arenas, institutions, the administrative state, and the professions of policy analyst and public management. In addition, the case method that figures prominently in MPA pedagogy and the research MPA students perform depend on doing history. Yet, history as a scholarly endeavor is rarely included in basic courses, much less instruction in research methods. This essay explores the use of history in MPA curricula and how MPA students might acquire a deeper appreciation of history and how historians ply their craft.

Uncertain Hazards: Environmental Activists and Scientific Proof. By Sylvia Noble Tesh. Ithaca, NY: Cornell University Press, 2000. 192p.

Uncertain Hazards is an ambitious book, in two respects. First, it tackles an important issue for political science as well as sociology and history, namely, the impact that social movements have on reshaping the societies in which they mobilize. Second, in adopting a case study approach to this issue, the author explores the development of the modern environmental movement and its purported reframing or hegemonic reversal of environmental science and risk assessment in America. In effect, this volume is two separate but related studies. Indeed, Sylvia Noble Tesh suggests as much when she notes in her acknowledgments that her “theme shifted as the book took shape” (p. xi).