Use of fMRI to predict psychiatric adverse effects of interferon treatment for Hepatitis C – preliminary report

Interferon alfa2 (IFN-α2) is a parenterally administered cytokine used to treat patients with Hepatitis C and B, and malignancy. Interferon (INF) has a relatively high rate of central nervous system (CNS) adverse effects, including agitation, depression, fatigue, cognitive dysfunction, suicidal thought and drug craving. Using functional magnetic resonance imaging (fMRI) we studied patients with Hepatitis C virus (HCV) infection who were not more than mildly clinically depressed at baseline for their CNS reaction to IFN-α2. During fMRI, patients underwent visual stimulation with pictures designed to induce feelings of depression. In the two patients who became clinically depressed or markedly anxious while on treatment with interferon, but not in patients who did not experience these effects, there was a significant activation in specific areas of the brain known to be involved with depression, along with an increase above baseline in the Beck Depression Scale for the patient who developed INF-induced depression. The activation pattern differed from that previously observed for endogenous depression, indicating that INF-induced depression may differ in its underlying neuropathology. Functional magnetic resonance imaging can be an important tool in understanding and monitoring for (INF and other) medication-induced CNS effects, and response to treatment.     

Teaching scholars programs: faculty development for educators in the health professions.

OBJECTIVE: This article 1) provides an overview of formal Health Sciences Teaching Scholars Programs as presented in medical education literature and 2) presents information about an innovative multidiscipline Teaching Scholars Program. METHOD: Health Sciences Teaching Scholars Programs and similar programs were reviewed in the medical education literature to identify similar and dissimilar characteristics. The WVU Teaching Scholars Program highlighted in this article is presented with a discussion of goals, objectives, target audiences, course length, session frequency, program topics, learning methods, and assessments of the programs. A summary of the WVU Teaching Scholars Program and two Teaching Scholars Programs at McGill University and the University of Toronto were presented at the Association for American Medical Colleges (AAMC) annual meeting in 2006 for input from the general medical education audience. RESULTS: Comparisons of Health Sciences Teaching Scholars Programs reveal that successful programs are uniquely shaped by their educational environments. Scholars report that they value learning new teaching methods and improving their educational careers. CONCLUSION: Teaching Scholars Programs are valuable for the development of enhancing both teaching and scholarship in Health Sciences Programs and must adapt to the uniqueness of their respective educational environments and must continue to nurture scholars beyond graduation.     

Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial.

PURPOSE: To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma. PATIENTS AND METHODS: A total of 283 eligible patients with pT3-4a and/or node-positive disease were randomly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL (Wellferon, Burroughs-Wellcome, Research Park, NC) given daily for 5 days every 3 weeks for up to 12 cycles. Patients were stratified on the basis of pathologic stage. Patients remained on treatment until documented recurrence, excessive toxicity, or patient/physician preference deemed removal appropriate. RESULTS: At median follow-up of 10.4 years, median survival was 7.4 years in the observation arm and 5.1 year in the treatment arm (log-rank P =.09). Median recurrence-free survival was 3.0 years in the observation arm and 2.2 years in the interferon arm (P =.33). Performance status (P =.003), nodal status (N2 v N0, P <.0001), and tumor stage (P =.0002) were significant prognostic factors in multivariate analysis. A proportional hazards model examining the effects of treatment arm and time to recurrence on survival after recurrence among patients who recurred found that random assignment to interferon treatment (P =.009) and shorter time to recurrence (P <.0001) were independent predictors of shorter survival after recurrence. Although no lethal toxicities were observed, severe (grade 4) toxicities including neutropenia, myalgia, fatigue, depression, and other neurologic toxicities occurred in 11.4% of those randomly assigned to interferon treatment. CONCLUSION: Adjuvant treatment with interferon did not contribute to survival or relapse-free survival in this group of patients.     

Plasma lecithin-cholesterol acyltransferase activity and plasma lipoprotein composition and concentrations in kwashiorkor

Plasma lecithin-cholesterol acyltransferase (LCAT) activity, lipoprotein composition, and lipoprotein concentrations were measured in 21 children with kwashiorkor before (day 1), during (day 10), and after treatment (day 30). Day 1 LCAT activity (78.2 mumol.L-1.h-1) was decreased with respect to day 10 (139.2 mumol.L-1.h-1, P less than 0.001) and day 30 (108.0 mumol.L-1.h-1, P = 0.08). Plasma total cholesterol (TC), cholesterol ester (CE), and lipoprotein CEs (VLDL, IDL, LDL, and HDL) were reduced relative to days 10 and 30 (P less than 0.001). Before treatment HDL composition was abnormal. On days 1, 10, and 30, the respective mean HDL-apolipoprotein A-I (apo A-I) concentrations were 23.33, 39.66, and 36.08 mumol/L. LDL-apo B concentrations were 0.40, 0.68, and 0.56 mumol/L (P less than 0.01, days 10 and 30 vs day 1). LDL particles on day 1 were decreased in number, depleted of CE, and laden with triacylglycerol and surface lipids. LCAT activity on day 1 correlated with LDL-CE linoleate (P less than 0.05, r = 0.48). Reduced plasma LCAT activity is an important factor related to abnormalities in lipoprotein composition and concentrations.     

Failure of ivalon to provide permanent hepatic arterial occlusion

Ivalon (polyvinyl alcohol) is a commonly used embolic agent, generally considered to be permanent. In a patient with the carcinoid syndrome, embolization of hepatic metastases with Ivalon failed to produce permanent occlusion, and recurrent tumor was supplied by many of the same small arteries identified on the original arteriogram. Occasionally, Ivalon may have only a temporary occlusive effect. A possible explanation for this phenomenon is proposed.