We conducted patient-oriented clinical research in neurocardiology. Studies focused on elucidating pathophysiologic mechanisms and developing novel diagnostic approaches for disorders involving altered regulation of catecholamine systems. These conditions result from dysfunction of the autonomic nervous system (dysautonomia) or abnormally decreased or increased production of the catecholamines, norepinephrine (NE), epinephrine (EPI), or dopamine (DA). Patients with autonomic failure in the setting of Parkinson's disease all had cardiac sympathetic denervation, detected by 6-[18F]fluorodopamine positron-emission tomographic scanning. In contrast, patients with multiple system atrophy, which can be difficult to distinguish clinically from Parkinson's disease, all had evidence for intact cardiac sympathetic nerve terminals. Even in the absence of autonomic failure, most patients with Parkinson's disease had evidence for localized or diffuse loss of cardiac sympathetic nerve terminals. In the diagnostic evaluation of pheochromocytoma, a clinically important tumor that produces catecholamines, plasma levels of metanephrines, metabolites of NE and EPI made in the tumor, provided a uniquely and virtually perfectly sensitive screening test. 6-[18F]Fluorodopamine positron-emission tomographic scanning successfully localized the tumor even in difficult cases. A combined neurogenetic and neurochemical approach holds great promise for understanding how particular mutations in familial diseases associated with increased production of NE (pheochromocytoma) or decreased production of NE (Menkes disease) relate to particular neurochemical and clinical manifestations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002979-02
Application #
6432944
Study Section
(CNCS)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2000
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Goldstein, David S; Eisenhofer, Graeme; Kopin, Irwin J (2006) Clinical catecholamine neurochemistry: a legacy of Julius Axelrod. Cell Mol Neurobiol 26:695-702
Sharabi, Yehonatan; Eldadah, Basil; Li, Sheng-Ting et al. (2006) Neuropharmacologic distinction of neurogenic orthostatic hypotension syndromes. Clin Neuropharmacol 29:97-105
Gamboa, Alfredo; Gamboa, Jorge L; Holmes, Courtney et al. (2006) Plasma catecholamines and blood volume in native Andeans during hypoxia and normoxia. Clin Auton Res 16:40-5
Goldstein, David S (2006) Orthostatic hypotension as an early finding in Parkinson's disease. Clin Auton Res 16:46-54
Li, Sheng-Ting; Eldadah, Basil A; Sharabi, Yehonatan et al. (2006) Coronary vascular resistance in primary chronic autonomic failure. Clin Auton Res 16:293-5
Eldadah, Basil A; Pechnik, Sandra L; Holmes, Courtney S et al. (2006) Failure of propranolol to prevent tilt-evoked systemic vasodilatation, adrenaline release and neurocardiogenic syncope. Clin Sci (Lond) 111:209-16
Holmes, Courtney; Moak, Jeffrey; Eldadah, Basil et al. (2005) Dopamine contamination of infused tyramine. Clin Chem 51:1733-5
Eisenhofer, Graeme; Huysmans, Frans; Pacak, Karel et al. (2005) Plasma metanephrines in renal failure. Kidney Int 67:668-77
Huynh, Thanh-Truc; Pacak, Karel; Brouwers, Frederieke M et al. (2005) Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2. Eur J Endocrinol 153:551-63
Gold, Philip W; Wong, Ma-Li; Goldstein, David S et al. (2005) Cardiac implications of increased arterial entry and reversible 24-h central and peripheral norepinephrine levels in melancholia. Proc Natl Acad Sci U S A 102:8303-8

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