Diabetes Is Associated with Cerebrovascular but not Alzheimer\u27s Disease Neuropathology

INTRODUCTION: The relationship of diabetes to specific neuropathologic causes of dementia is incompletely understood. METHODS: We used logistic regression to evaluate the association between diabetes and infarcts, Braak neurofibrillary tangle stage, and neuritic plaque score in 2365 autopsied persons. In a subset of \u3e1300 persons with available cognitive data, we examined the association between diabetes and cognition using Poisson regression. RESULTS: Diabetes increased odds of brain infarcts (odds ratio [OR] = 1.57, P \u3c .0001), specifically lacunes (OR = 1.71, P \u3c .0001), but not Alzheimer\u27s disease neuropathology. Diabetes plus infarcts was associated with lower cognitive scores at end of life than infarcts or diabetes alone, and diabetes plus high level of Alzheimer\u27s neuropathologic changes was associated with lower mini-mental state examination scores than the pathology alone. DISCUSSION: This study supports the conclusions that diabetes increases the risk of cerebrovascular but not Alzheimer\u27s disease pathology, and at least some of diabetes\u27 relationship to cognitive impairment may be modified by neuropathology

Service Productivity in Urban Drug Abuse Treatment Organizations.

Service productivity, a facet of service delivery which is defined here for the first time, is investigated in a sample of 24 urban drug treatment organizations in six major American cities. Both qualitative and quantitative analyses are brought to bear on the question of how service productivity is determined in 12 methadone clinics and 12 therapeutic communities. Drug programs are discussed as examples of organizations highly vulnerable to external influences. The study includes both multiple regression analyses of environmental and organizational characteristics that affect the production of services in treatment agencies and a case study that examines four drug programs in Miami and four programs in Detroit in detail, as well as contrasting the Miami and Detroit environments as examples of the supportive-hostile continuum of city environments proposed here. The concepts of adaptive stance and service productivity are introduced as new variables to be included in a model of human service organizations. Results indicate that urban environment can indeed be characterized using the notions of hostility-supportiveness and that urban setting affects these vulnerable organizations' choice of subsidiary or autonomous stance regarding that environment, as well as technology and resources. These contextual characteristics are shown to influence goal ideologies, size, staffing and other internal characteristics. The environmental and organizational characteristics taken together influence the production of services in urban drug treatment organizations.Ph.D.Public policyUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/158515/1/8125189.pd

State substance abuse agencies and their placement within government impact on organizational performance and collaboration in 12 states

Title from PDF p. [1] (viewed Oct 31, 2006).; "... Supported by the Center for Substance Abuse Treatment (CSAR)[, Substance Abuse and Mental Health Services Administration (SAMHSA, USDHHS] through Contract No. 270-00-7071 with Health Systems Research, Inc. (HSR)."; "November 2005."; Covers: California, Florida, Georgia, Maine, Massachusetts, Michigan, New York, North Carolina, Ohio, Oregon, Texas, and Washington.; Includes bibliographical references.; Harvested from the web on 11/6/0

Chronic Progressive Cardiac Dysfunction Years After Doxorubicin Therapy for Childhood Acute Lymphoblastic Leukemia

Purpose Cross-sectional studies show that cardiac abnormalities are common in long-term survivors of doxorubicin-treated childhood malignancies. Longitudinal data, however, are rare. Methods Serial echocardiograms (N = 499) were obtained from 115 doxorubicin-treated long-term survivors of childhood acute lymphoblastic leukemia (median age at diagnosis, 4.8 years; median follow-up after completion of doxorubicin, 11.8 years). Results were expressed as z scores to indicate the number of standard deviations (SDs) above (+) or below (−) the normal predicted value. Median individual and cumulative doxorubicin doses were 30 mg/m2 per dose and 352 mg/m2, respectively. Results Left ventricular fractional shortening was significantly reduced after doxorubicin therapy, and the reduction was related to cumulative dose. z scores for fractional shortening transiently improved before falling to −2.76 more than 12 years after diagnosis. Reduced fractional shortening was related to impaired contractility and increasing afterload, consequences of a progressive reduction of ventricular mass, and wall thickness relative to body-surface area. Left ventricular contractility fell significantly over time and was depressed at last follow-up in patients receiving more than 300 mg/m2 of doxorubicin. Systolic and diastolic blood pressures were below normal more than 9 years after diagnosis. Even patients receiving lower cumulative doxorubicin doses experienced reduced mass and dimension. Fractional shortening and dimension at the end of therapy predicted these parameters 11.8 years later. Conclusion Cardiac abnormalities were persistent and progressive after doxorubicin therapy. Inadequate ventricular mass with chronic afterload excess was associated with progressive contractile deficit and possibly reduced cardiac output and restrictive cardiomyopathy. The deficits were worst after highest cumulative doses of doxorubicin, but appeared even after low doses

Long-Term Enalapril Therapy for Left Ventricular Dysfunction in Doxorubicin-Treated Survivors of Childhood Cancer

PURPOSE: A common late effect of doxorubicin therapy for childhood cancer is reduced left-ventricular (LV) wall thickness resulting in elevated LV afterload and depressed LV function. Many children are given angiotensin-converting enzyme inhibitors, which have been studied primarily in adults. We document the long-term effects of angiotensin-converting enzyme inhibitors in doxorubicin-treated survivors of childhood cancer. PATIENTS AND METHODS: In this retrospective study, we reviewed records of 18 children who had regular echocardiographic examinations during enalapril therapy (mean age at cancer diagnosis, 8 years; mean time between completion of doxorubicin therapy and start of enalapril, 7 years; median follow-up since the start of enalapril, 10 years). RESULTS: Over the first 6 years of enalapril therapy, there was progressive improvement toward normal values in LV dimension, afterload, fractional shortening, and mass, but all these parameters deteriorated between 6 and 10 years. LV wall thickness deteriorated throughout the study period, as did LV contractility and systolic blood pressure. Diastolic blood pressure fell slightly. By 6 years on enalapril, all six patients who had had congestive heart failure at the start of enalapril therapy had either died or undergone cardiac transplantation, compared with three of the 12 asymptomatic patients. CONCLUSION: In doxorubicin-treated long-term survivors of childhood cancer, enalapril-induced improvement in LV structure and function is transient. The primary defect, which is LV wall thinning, continues to deteriorate, and thus the short-term improvement was mostly related to lowered diastolic blood pressure

Female Sex and Higher Drug Dose as Risk Factors for Late Cardiotoxic Effects of Doxorubicin Therapy for Childhood Cancer

There are more than 150,000 survivors of childhood cancer in the United States, 1 a group that is steadily increasing. By the year 2010, 1 of every 250 adults from 15 to 45 years of age in this country may be a survivor of childhood cancer. 1 Children with common cancers, including sarcomas, and some children with acute lymphoblastic leukemia are frequently treated with the anthracycline doxorubicin. 2 Anthracyclines improve survival of children with cancer, 3 , 4 but at the expense of cardiotoxicity that is related to the cumulative dose of these drugs. 5 Accordingly, for the past 16 years, treatment protocols have limited cumulative . .