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Biomedical subjects

A H Anton

Publications and source records attributed to A H Anton.

At least 19 recordsLinked to original sources

An atrial pheochromocytoma-induced hypertensive crisis resistant to nitroprusside.

A malignant pheochromocytoma with several unique features was studied. Initially, its histological and catecholamine secretory properties and physiological effects were terminated by an infarct prior to its excision in 1973. However, in 1985 a metastasis was resected from the right atrium. Hypertensive crisis during surgery was controlled by the administration of phentolamine but not by nitroprusside. Within 2 months, it was again detected at this same site. Biochemical studies confirmed its recurrence. The tumor did not respond to chemotherapy with vincristine, cyclophosphamide and dacarbazine, but there has been physiological and biochemical improvement from inhibiting catecholamine biosynthesis with metyrosine. We recommend that both phentolamine and sodium nitroprusside be readily available during resection of a pheochromocytoma.

Adrenal Gland Neoplasms

The "anesthetic" effect of alcohols and alkanes in Caenorhabditis elegans (C.e.).

In order to help validate the free-living roundworm, C.e., as a simple model to study the mechanism of general anesthesia, we demonstrated that homologous series of alcohols and alkanes produced a reversible "anesthetic" effect in these worms as in other animals. Also, as in other animals, the potency of these compounds was directly related to their respective lipid solubilities within each series. The alcohols were much more potent than the alkanes even though the latter were much more lipid soluble than the alcohols. The cut-off point (a decrease followed by a loss of activity) for these compounds occurred at about C9. In mice, the alcohols had an effect analogous to that seen in C.e. but the alkanes were inactive after intraperitoneal injection.

Alcohols

Epinephrine-aminophylline-induced arrhythmias after midazolam or thiopentone in halothane-anaesthetized dogs.

The purpose of this study was to evaluate epinephrine-aminophylline-induced arrhythmias during halothane anaesthesia after induction with thiopentone or midazolam. Ten mongrel dogs were studied during 1 MAC halothane and 50% N2O:O2 anaesthesia while maintaining constant acid-base status. The minimal arrhythmogenic infusion rate of epinephrine (MAIRE) and the corresponding plasma concentration of epinephrine (MAPC) required to produce ventricular arrhythmias before and after aminophylline were higher following induction of anaesthesia with midazolam than with thiopentone (P less than 0.05); the MAIREs decreased stepwise with aminophylline (P less than 0.05). The correlation coefficient between individual MAIREs and MAPCs was 0.93 (P less than 0.001). Epinephrine alone and in combination with aminophylline was less arrhythmogenic after induction with midazolam than with thiopentone.

Aminophylline

Flow cytometry DNA ploidy analysis and catecholamine secretion profiles in neuroblastoma.

Previous studies have shown that catecholamine secretion patterns have been imperfect predictors of clinical behavior of neuroblastomas. Recently, studies of nuclear DNA content in neuroblastoma have shown that an aneuploid DNA content predicts favorable clinical behavior. To determine if a correlation exists between these tumor biologic indicators, the authors analyzed both in a series of 39 patients with neuroblastoma. Flow cytometric DNA analysis performed on paraffin blocks determined that 23 patients had tumors with aneuploid DNA content (aneuploid tumors) and 16 patients showed no demonstrable anomalies of tumor DNA content (nonaneuploid tumors). Comparison of catecholamine levels in urine and tumor homogenates with DNA content data indicate that nonaneuploid neuroblastomas include a significant number (P less than 0.02) of biochemically primitive tumors which secrete high levels of 3,4 dihydroxyphenylalanine (DOPA), dopamine and homovanillic acid (HVA). This suggests a dopamine-norepinephrine pathway block, which supports previous reports of deficiency of dopamine beta-hydroxylase activity in some neuroblastomas. The study shows that in contrast to aneuploid tumors, nonaneuploid neuroblastomas secrete higher levels of early pathway catecholamine metabolites and are more likely to present in higher (unfavorable) clinical stages of disease.

Aneuploidy

Evaluation and improvement of homovanillic acid methodology, and a critique of liquid chromatography with electrochemical detection.

Resolution of several problems encountered with some organic solvent extraction-fluorometric procedures commonly used to measure homovanillic acid (HVA) in urine resulted in a more specific and sensitive methodology, applicable to diverse biological material. Purification on an anion-exchange resin followed by extraction with organic solvent was the most reliable and specific for HVA. Eluting the resin with a near-boiling solution of NaCl concentrated the HVA in a smaller volume with no increase in the blank reading. In none of the other methods was enough oxidizing agent used to completely oxidize the excessive amounts of HVA in urines of patients with neuroblastoma. 5-Hydroxyindoleacetic acid interferes with the HVA fluorophor. Several of the advantages and problems with "high-pressure" liquid chromatography with electrochemical detection are identified, particularly the unpredictable nature of the working electrode.

Chromatography, Liquid

Clonidine suppression test for pheochromocytoma: examples of misleading results.

Baseline plasma norepinephrine (NE) and epinephrine (E) levels over 2000 pg/ml or failure to suppress to less than 500 pg/ml after oral clonidine have been considered diagnostic of the presence of a pheochromocytoma. We found a false negative clonidine suppression test in a patient with an asymptomatic ACTH-secreting pheochromocytoma who had minimally increased resting plasma NE and E values of 669 and 419 pg/ml, respectively. Clonidine suppression caused decreases at 2 and 3 h to 372 and 408 pg/ml, respectively. A positive test was found in a patient with repeatedly elevated baseline plasma NE and E concentrations; the two highest results were 2501 and 3022 pg/ml. Clonidine administration on five occasions failed to decrease plasma NE and E levels to less than 500 pg/ml. However, no pheochromocytoma was found by selective venous catheterization, two laparotomies, and, ultimately, postmortem examination. Diffuse infiltration of lymphoplasmacytic cells throughout sympathetic ganglia and adrenal medulla raise the possibility of a diffuse autoimmune disorder, resulting in excessive catecholamine production. These examples suggest that the clonidine suppression test does not always indicate the presence or absence of a pheochromocytoma.

Adrenal Gland Neoplasms

Effects of low-dose morphine and fentanyl infusions on urinary and plasma catecholamine concentrations during scoliosis surgery.

Plasma and urinary catecholamines were measured in 20 patients during scoliosis surgery to determine whether low dose fentanyl (1.5-2.5 micrograms . kg-1 . min-1) and morphine (150-250 micrograms . kg-1 . min-1) affect the catecholamine stress response to surgery differently. In all patients epinephrine (1.6-11.4 micrograms/kg) was injected locally at the operative site for hemostasis. This was an advantage because exogenous and endogenous epinephrine undergo the same fate and the increase in epinephrine might enhance otherwise subtle effects. The data indicate that both narcotics have similar effects on catecholamine metabolism but that even low doses of fentanyl are more effective than morphine in obtunding the catecholamine response to painful stimuli. Also, postoperative differences in plasma epinephrine indicate that recovery of awareness, and thus the onset of postoperative pain, is more rapid in patients receiving fentanyl.

Adolescent

Noninvasive assessment of electroconvulsive-induced changes in cardiac function.

Systolic time intervals were used to noninvasively evaluate the cardiac effects of electroconvulsive therapy (ECT) in eight psychiatric patients. ECT produced a hyperdynamic cardiac state in which there was a significant increase in blood pressure, a shortening of the pre-ejection period (PEP), and an increase in rate pressure product (RPP). Changes in the PEP and the RPP are compatible with increased cardiac contractility and oxygen consumption, respectively. These effects were apparently mediated by an ECT-induced increase in circulating catecholamines, particularly epinephrine.

Adolescent

A simple, reliable and rapid method for increasing the responsiveness of the glassy carbon electrode (GCE) for the analysis of biogenic amines by high performance liquid chromatography with electrochemical detection (LCEC).

A simple procedure has been devised for reversing the passivation of the GCE that occurs during electrochemical analyses. Alumina polishing is unpredictable in that occasionally it may worsen the problem. The present procedure involves treating the GCE with a CrO3-H2SO4 solution. It is fast (30 seconds), reliable, and increases the responsiveness of the electrode above that obtainable by alumina polishing.

Carbon

Beneficial hemodynamic effects of oral levodopa in heart failure. Relation to the generation of dopamine.

Among the positive inotropic drugs available to improve myocardial contractility in congestive heart failure, only digitalis glycosides are suitable for oral administration. In this study, we administered oral levodopa (1.5 to 2.0 g), which is decarboxylated to form dopamine, to 10 patients with severe congestive heart failure. Peak hemodynamic responses occurred one hour after the ingestion of levodopa, with the mean (+/- S.E.M.) cardiac index increasing from 1.8 +/- 0.1 to 2.4 +/- 0.2 liters per minute per square meter of body-surface area (P less than 0.01) and systemic vascular resistance declining from 1905 +/- 112 to 1513 +/- 121 dyn X sec X cm-5 (P less than 0.01). These effects persisted for four to six hours. Left ventricular filling pressure, heart rate, and mean arterial pressure were unchanged. Plasma concentrations of dopamine rose to a peak level of 34 +/- 5 ng per milliliter one hour after drug ingestion and decreased toward base line over the ensuing five hours. A significant correlation was observed between plasma dopamine levels and changes in cardiac index (r = 0.8; P less than 0.02). Five patients enrolled in a trial to evaluate the effectiveness of long-term therapy with levodopa had similar hemodynamic responses to the drug after 6.8 +/- 1.7 months of treatment. Thus, oral administration of levodopa to patients with severe heart failure produced a sustained improvement in cardiac function. The hemodynamic responses observed can be attributed to the activation of beta 1-adrenergic, dopamine, and dopamine receptors by dopamine derived from levodopa.

Administration, Oral

The effect of manganese inhalation on basal ganglia dopamine concentrations in rhesus monkey.

Manganese (Mn) may produce neurotoxicity in man through inhalation of Mn dust. Animals exposed to excessive Mn develop neurological abnormalities, and neuropathological lesions in the brain mainly in the globus pallidus with decreased concentrations of the neurotransmitter, dopamine (DA), in the brain. Monkeys exposed to Mn by inhalation did not produce any abnormal movements. After two years, the animals were sacrificed and certain brain areas were compared to controls. There were significant decreases in DA concentration in caudate and globus pallidus, and there was a 60-80% increase in Mn concentration in the basal ganglia of the brain. The DA system in the basal ganglia is vulnerable to the effects of Mn, but the amount of Mn inhaled and the period of exposure would appear to determine whether abnormal neurological signs develop.

Animals

Tumor and urine catecholamines (CATs) in neurogenic tumors. Correlations with other prognostic factors and survival.

This study was undertaken to better define the relationship between catecholamine (CAT) metabolism within the malignant neuroblast and other factors known to influence clinical outcome in neuroblastoma (NB). Several CATs and their metabolites were measured in 32 tumors and 47 urines from 60 newly diagnosed children with neurogenic tumors. Absolute and relative CAT concentrations were correlated with age, clinical stage, histologic differentiation and survival duration. The major findings are: (1) urinary CAT excretion patterns often differ markedly from tumor CAT patterns in the same child, which may be explained by the continuous nature of tumor metabolism, hepatic and renal catabolism, and sampling errors; (2) definite patterns of biochemical maturation are apparent in tumors and urines, but standard light microscopy is insufficient to correlate this with degree of histologic differentiation; (3) more differentiated patterns of CAT metabolism, both in tumor and urine, are significantly associated with age less than 1 year at diagnosis, and with more favorable clinical Stage (I, II, IVS). Tumor NE was increased relative to DM and DA, and urine NMN and VMA were increased relative to DM and HVA, in these patients. (4) this more differentiated CAT pattern in infants and in less advanced stages was reflected in their better survival. Greater maturity of tumor enzyme systems is the probable reason for the better prognosis of NB in infants less than 1 year. Individual enzymes should be measured in fresh tumor tissues, and related to relative and absolute CAT concentrations in tumor and urine, to try to categorize patients on the basis of clearcut biological differences when planning new treatment strategies for NB.

Age Factors

Inhibition of catecholamine biosynthesis by carbidopa and metyrosine in neuroblastoma.

In three patients with neuroblastoma and high circulating levels of dopamine and dopa, we interfered pharmacologically with catecholamine biosynthesis either at the tyrosine hydroxylase or dopa decarboxylase step in an attempt to 1) improve the efficacy of antitumor therapy and 2) avoid the potential arrythmogenic interaction between elevated circulating catecholamines and an halogenated hydrocarbon anesthetic during surgery. Biochemical evidence indicated that inhibition of catecholamine biosynthesis had occurred but there was no associated significant change in clinical status or response to other therapy.

Carbidopa

Phenothiazine biphasic effect on dopamine concentrations in the basal ganglia of subhuman primates.

Interpretation of data on the possible relationship between changes in endogenous putative transmitters and neuropsychiatric disorders may be altered by the use of neuroleptic agents. As one approach to this problem, we attempted to simulate the situation in man by measuring the changes in dopamine in basal ganglia of monkeys during the chronic (20 months) administration of an antipsychotic phenothiazine. Unexpectedly, a biphasic response was obtained: dopamine increased after 2 months but was markedly reduced after 20 months. Perhaps, dyskinesia is related to this biphasic effect of the antipsychotic phenothiazines.

Animals