Decreased taste sensitivity after D-penicillamine reversed by copper administration.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to H R Keiser.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Magnetic resonance imaging (MRI) of seven patients with pheochromocytomas demonstrable by CT was performed. Magnetic resonance imaging showed all primary pheochromocytomas, as well as metastatic lesions to the thorax, retroperitoneum, and liver. The ability to distinguish pheochromocytomas from surrounding structures without the need of an intravenous contrast agent and to provide direct coronal and sagittal images suggests that MRI may be useful in detecting and localizing these tumors.
We simultaneously infused tracer-labeled norepinephrine (NE) and isoproterenol (ISO) intravenously into 14 subjects to measure forearm and total body NE pharmacokinetics at rest and in response to mental challenge (video game or cognitive task). Mental challenge was associated with significantly increased heart rate (24%), systolic blood pressure (13%), cardiac output (impedance cardiography, 9%), forearm blood flow (38%), and the rate of release of endogenous NE into arterial blood (total body NE spillover, 29%), but not with changes in cardiac output (r = 0.68) and systolic blood pressure (r = 0.60), whereas those of antecubital venous NE were not. Forearm extraction of NE was related inversely to forearm blood flow both at rest (r = -0.80) and during mental challenge (r = -0.81), and total body clearance of NE was positively related to cardiac output at rest (r = 0.78) and during mental challenge (r = 0.54). The results indicate that mental challenge is associated with generally increased sympathetically-mediated NE release that determines the hemodynamic responses. Because of regional changes in sympathetic activity and blood flow during psychological stress, changes in antecubital venous NE and even arterial NE may not reflect accurately sympathetic nerve activity. Measurement of total body and regional NE pharmacokinetics avoids these difficulties.
Because isoprenaline is not a substrate for neuronal uptake (Uptake-1, U-1), the difference in regional removal of isoprenaline from regional removal of the sympathetic neurotransmitter noradrenaline has been proposed as an index of regional U-1 activity. U-1 activity has not been assessed in the kidney, where decreased U-1 may account for increased renal spillover of noradrenaline into plasma in disorders such as essential hypertension. Tracer-labelled noradrenaline and isoprenaline were simultaneously infused intravenously into anaesthetized dogs, and the regional removal of noradrenaline and isoprenaline was measured in the hindlimb and kidney after administration of the U-1 blocker desipramine, hydrocortisone, which inhibits extra-neuronal uptake of noradrenaline (Uptake-2, U-2), or no drug. Hindlimb removal of noradrenaline (51%) exceeded that of isoprenaline (36%). Desipramine abolished this difference by decreasing removal of noradrenaline without affecting removal of isoprenaline. Renal removal of isoprenaline exceeded that of noradrenaline (74% vs 54%) even after U-1 blockade. Hydrocortisone did not affect removal of noradrenaline or isoprenaline in either bed. The results suggest that differences in removal of noradrenaline and isoprenaline reflect U-1 activity in the hindlimb but not in the kidney; U-1 is much more important than U-2 in the regional removal of noradrenaline; and one mechanism of noradrenaline removal in the kidney is by neuronal uptake.
Explore the source record for details and available documents.
The effect of alterations in extracellular fluid volume (ECV) and solute concentration on excretion of urinary kallikrein was examined in conscious Sprague-Dawley rats. Animals were given infusions of either dextrose and water, saline, or albumin according to a variety of protocols. These were designed to evaluate possible relationships between excretion of kallikrein, volume, sodium, and potassium. A reproducible pattern of kallikrein excretion was noted in all volume expanded groups. This consisted of a short lived increase during the initial hour of expansion with a subsequent fall to lower levels than baseline and a gradual recovery. To define the role of aldosterone in these studies, an adrenalectomized group and a group of appropriately prepared sham controls were expanded with saline. Adrenalectomy did not effect this pattern. We postulate a tubular "washout" phenomenon as the etiology of these observations. Results of these studies fail to demonstrate a consistent relationship between urinary volume, sodium, or potassium and the simultaneous amount of kallikrein found in the urine.
We compared venous plasma norepinephrine (NE) concentrations in 191 resting, supine patients with essential hypertension and 129 normotensive controls. Among normotensives, plasma NE increased significantly with age, but among hypertensives, no age-related increase occurred, due to relatively high NE values among young hypertensives. When patients and controls less than 40 years old were considered, hypertensives showed significantly higher plasma NE than the controls (317 vs 245 pg/ml, t = 3.15, p less than 0.01); but above the age of 40 years, no significant hypertensive-normotensive difference was obtained. These results, predicted by recent literature reviews, help to resolve the persistent controversy about sympathetic neural activity in essential hypertension, since such activity appears to be abnormal mainly in young patients. The data are consistent with increased sympathetic nervous system activity in the early stages of essential hypertension.
Vascular renin-like activity was studied in the aortas and the cerebral microvessels of Sprague-Dawley rats and in the aortas of spontaneously hypertensive rats. Methods were employed to maximize detection of tissue renin and to simultaneously minimize contamination of that activity by either plasma renin or nonspecific proteases capable of angiotensin I generation. To this end, renin activity was measured near its pH optimum; plasma renin was eliminated by nephrectomy; and nonspecific proteases such as cathepsin D were either inhibited by proteolytic blockers or removed by chromatography over immobilized bovine hemoglobin. Aortic vascular renin-like activity was detected in rats not subjected to nephrectomy and could be inhibited by preincubation of samples with antimouse renin antibody shown to cross-react and inhibit rat plasma renin activity. Furthermore, vascular renin-like activity disappeared after nephrectomy in parallel with the disappearance of plasma renin activity. In the absence of contaminating enzymatic activities, no tissue renin-like activity could be demonstrated in either aortas or cerebral microvessels of Sprague-Dawley rats or in aortas of spontaneously hypertensive rats.
Three patients with rapidly progressive, disseminated malignant pheochromocytoma were treated with a combination chemotherapeutic regimen consisting of cyclophosphamide, vincristine, and dacarbazine in repeated 21- to 28-day cycles. All three patients had a marked decrease in blood pressure and an improvement in performance status within the first few cycles of treatment. At a follow-up of 6 to 13 months all patients continue to receive chemotherapy with further regression of tumor in two and stable disease in one. Their blood pressure is normal with minimal or no antiadrenergic therapy. Therapy has been well tolerated; moderate reversible granulocytopenia, neurotoxicity, and one episode of pneumonitis have been the major toxicities encountered. Thus, combination chemotherapy appears to be effective for symptomatic malignant pheochromocytoma.