Pursuant to the Section?s mission of conducting mainly patient-oriented clinical research on neurocardiologic disorders, with an emphasis on catecholamine systems, we studied patients with chronic autonomic failure (e.g., Parkinson disease with orthostatic hypotension (PD+OH)), chronic orthostatic intolerance (COI), pheochromocytoma (Pheo), and congenital inherited diseases involving abnormal catecholamine biosynthesis. Major findings and inferences: (1) We obtained neuroimaging, neurochemical, and pharmacologic evidence that PD+OH entails loss of cardiac and extra-cardiac noradrenergic nerves, providing further support for the notion that PD+OH is not only a movement disorder but also a form of dysautonomia. (2) We succeeded in using the NIH Clinical Center's High Resolution Research Tomograph to delineate central catecholaminergic innervation in patients with PD, multiple system atrophy, or pure autonomic failure and preliminarily have noted strongly positive correlations between neuroimaging and CSF neurochemical indices of central dopamine deficiency. (3) We identified another patient with autoimmune autonomic failure, from a circulating antibody to the neuronal nicotinic receptor, and under a new clinical therapeutics protocol successfully treated the patient by total plasma exchange. (4) We found that patients with postural tachycardia syndrome, a common, mysterious, controversial form of COI, had findings consistent with secondary sympathetic noradrenergic and adrenomedullary activation in response to decreased venous return to the heart, rather than a primary abnormality of catecholamine release or reuptake. (4) In a double-blind, placebo-controlled, randomized crossover study, beta-adrenoceptor blockade did not prevent sympathoadrenal imbalance or neurocardiogenic syncope. (5) We continued a project on genetics of familial COI in a large French Canadian kindred. (6) We continued a project on mutation-dependent differences in tumor cell gene expression as a basis for different phenotypes and clinical manifestations of Pheo. (7) We continued to observe that patterns of plasma catechols diagnosed Menkes disease perfectly prospectively in at-risk newborns.
| 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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