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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Intramural Research (Z01)
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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
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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
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Goldstein, David S; Eldadah, Basil; Holmes, Courtney et al. (2005) Neurocirculatory abnormalities in chronic orthostatic intolerance. Circulation 111:839-45
Sharabi, Y; Zimlichman, R; Alesci, S et al. (2005) Glucagon does not affect catecholamine release in primary cultures of bovine adrenal chromaffin cells. Horm Metab Res 37:205-8
Singh, Ravinder J; Grebe, Stefan K; Yue, Bingfang et al. (2005) Precisely wrong? Urinary fractionated metanephrines and peer-based laboratory proficiency testing. Clin Chem 51:472-3; discussion 473-4

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