Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease

BACKGROUND: Abnormalities in cerebrospinal fluid (CSF) production and turnover, seen in normal pressure hydrocephalus (NPH) and in Alzheimer's disease (AD), may be an important cause of amyloid retention in the brain and may relate the two diseases. There is a high incidence of AD pathology in patients being shunted for NPH, the AD-NPH syndrome. We now report elevated CSF pressure (CSFP), consistent with very early hydrocephalus, in a subset of AD patients enrolled in a clinical trial of chronic low-flow CSF drainage. Our objective was to determine the frequency of elevated CSFP in subjects meeting National Institutes of Neurological and Communicative Diseases and Stroke – Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for AD, excluding those with signs of concomitant NPH. METHODS: AD subjects by NINCDS-ADRDA criteria (n = 222), were screened by history, neurological examination, and radiographic imaging to exclude those with clinical or radiographic signs of NPH. As part of this exclusion process, opening CSFP was measured supine under general anesthesia during device implantation surgery at a controlled pCO(2 )of 40 Torr (40 mmHg). RESULTS: Of the 222 AD subjects 181 had pressure measurements recorded. Seven subjects (3.9%) enrolled in the study had CSFP of 220 mmH(2)0 or greater, mean 249 ± 20 mmH(2)0 which was significantly higher than 103 ± 47 mmH(2)O for the AD-only group. AD-NPH patients were significantly younger and significantly less demented on the Mattis Dementia Rating Scale (MDRS). CONCLUSION: Of the AD subjects who were carefully screened to exclude those with clinical NPH, 4% had elevated CSFP. These subjects were presumed to have the AD-NPH syndrome and were withdrawn from the remainder of the study

Synthesis, characterization and catalytic applications of tantalum and niobium alkyl, alkylidene and olefin complexes

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1980.MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE.Includes bibliographical references.by Jere Douglas Fellmann.Ph.D

The effects of fenoldopam, a selective dopamine receptor agonist, on systemic and renal hemodynamics in normotensive subjects

OBJECTIVE:Acute renal failure, frequently a consequence of renal vasoconstriction and subsequent renal ischemia, is a common problem for which no proven preventive or therapeutic agents exist. Fenoldopam is a new, selective, dopamine-1 receptor agonist that causes both systemic and renal arteriolar vasodilation. In hypertensive patients, fenoldopam rapidly decreases blood pressure, increases renal blood flow, and maintains or improves the glomerular filtration rate. We sought to determine a dose of fenoldopam that increases renal blood flow without inducing hypotension in normotensive patients and to explore the role of volume status (sodium replete vs. deplete) in these effects. DESIGN:Randomized, double-blind, placebo-controlled, crossover study. SETTING:Clinical research unit. PATIENTS:Fourteen normal male volunteers. INTERVENTIONS:Renal plasma flow (para-aminohippurate clearance) and glomerular filtration rate (inulin clearance) were measured during three fixed, escalating doses of fenoldopam (0.03, 0.1, and 0.3 μg/kg/min) on both a high-sodium and a low-sodium diet. MEASUREMENTS AND MAIN RESULTS:Fenoldopam significantly increased renal plasma flow in a dose-dependent manner compared with placebo670 ± 148 vs. 576 ± 85 mL/min at 0.03 μg/kg/min; 777 ± 172 vs. 579 ± 80 mL/min at 0.1 μg/kg/min; and 784 ± 170 vs. 592 ± 165 mL/min at 0.3 μg/kg/min (p < .05 fenoldopam vs. placebo at all three doses). Glomerular filtration rate was maintained. At the lowest dose (i.e., 0.03 μg/kg/min), significant renal blood flow increases occurred without changes in systemic blood pressure or heart rate. At 0.1 and 0.3 μg/kg/min, systolic blood pressure did not change, but diastolic blood pressure was slightly lower in the fenoldopam group than in the placebo group62.5 ± 6.4 vs. 63.6 ± 2.6 mm Hg, respectively, at 0.3 μg/kg/min (p < .05). None of the effects of fenoldopam were altered by volume status. CONCLUSIONS:Fenoldopam increased renal blood flow in a dose-dependent manner compared with placebo, and, at the lowest dose, significantly increased renal blood flow occurred without changes in systemic blood pressure or heart rate. These findings will be useful in designing future studies exploring the role of fenoldopam in preventing or treating renal failure in patients who are not hypertensive