We conducted patient-oriented clinical research in neurocardiology. Studies focused on elucidating pathophysiologic mechanisms and developing novel diagnostic approaches for disorders of catecholamine systems. These conditions often involve dysfunction of the autonomic nervous system (dysautonomia), from abnormal production, release, or inactivation 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. Cardiac sympathetic denervation in Parkinson's was found to be independent of levodopa treatment, to progress over time, and to be present in familial Parkinson's disease arising from mutation of the gene encoding alpha-synuclein. 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. Chronic orthostatic intolerance occurs commonly in chronic fatigue syndrome, suggesting involvement of the autonomic nervous system. In patients with chronic orthostatic intolerance, a pattern of increased adrenomedullary hormonal system activity and inhibition of sympathetic nervous system activity (""""""""sympathoadrenal imbalance"""""""") was found to precede tilt-induced and spontaneously occurring neurocardiogenic syncope. Independent of acute episodes, patients with neurocardiogenic syncope had significantly decreased and with postural tachycardia syndrome significantly increased entry of NE into the venous drainage of the heart (cardiac NE spillover), consistent with both conditions being forms of dysautonomia.
| 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 |
| Eisenhofer, Graeme (2005) Sympathetic nerve function--assessment by radioisotope dilution analysis. Clin Auton Res 15:264-83 |
| Ohta, Shoichiro; Lai, Edwin W; Pang, Alan L Y et al. (2005) Downregulation of metastasis suppressor genes in malignant pheochromocytoma. Int J Cancer 114:139-43 |
| 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 |
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