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Biomedical subjects

M H Ebert

Publications and source records attributed to M H Ebert.

At least 19 recordsLinked to original sources

Norepinephrine elevations in cerebrospinal fluid after d- and l-amphetamine.

We continuously collected cerebrospinal fluid (CSF) from the lateral ventricles of monkeys and gave them from 0.1 to 1.0 mg/kg d- or l-amphetamine intravenously. The norepinephrine (NE) content of their CSF had a small circadian rhythm and a large increase after amphetamine. 1.0 mg/kg amphetamine gave a four-fold rise in CSF-NE which remained elevated for 33 h, smaller doses gave proportionately lesser responses. Both d- and l-amphetamine caused similar NE elevations except for minor differences at the highest dose. If there are differences in behavioral effects of moderate doses of d- and l-amphetamine, they are probably not due to a general difference in central NE release from these stereoisomers.

Amphetamine

Increased insulin binding to erythrocytes in anorexia nervosa: restoration to normal with refeeding.

We studied [125I] insulin binding to circulating cells in patients with anorexia nervosa (eight females), in the basal cachectic state (seven patients) and after weight gain (eight patients) and compared the values to those obtained in 17 normal volunteers (eight females and nine males). Untreated patients showed increased insulin binding to receptors on erythrocytes (mean +/- S.E.M., 12.2 +/- 0.99 per cent of total); after weight gain, these increased levels returned to normal (6.8 +/- 0.42 vs 6.7 +/- 0.63 per cent of total). Increased binding was due to an increased number of receptors per cell, with little or no change in receptor affinity. In five patients (one untreated, four treated), results of [125I] insulin binding to erythrocytes correlated closely (r = 0.982) with results obtained with monocytes. We conclude that in patients with anorexia nervosa, insulin binding to receptors is altered and that the abnormality is corrected by restoration of normal food intake and body weight.

Adolescent

Plasma levels of d-amphetamine in hyperactive children. Serial behavior and motor responses.

Amphetamine has been clearly documented to be an efficacious treatment for hyperactive children. The pharmacokinetics of amphetamine have been studied in adults, but not in children. Sixteen male children who scored greater than 2SD from norms on Factors I and IV of Conner's Teacher Rating Scale and who were not excluded for reasons to do with medical or psychiatric conditions, intelligence, or age, had a plasma d-amphetamine apparent elimination half-life of 6.8 +/- 0.5h. Peak plasma level occurred between 3 and 4h (62.7 +/- 3.8 and 65.9 +/- 3.6 ng/ml, respectively). Six of these children had a repeat study and there were no significant differences within subject in apparent elimination half-lives and attained peak blood levels. The variation in plasma levels was greater during absorption than during elimination. Both behavioral and motor activity responses as analyzed by differences between amphetamine and placebo days (by paired t-tests) indicate significant responses between hours 1--4; however, these responses do not correlate with plasma amphetamine levels; they occur during the absorption phase. The decreased response to later similar plasma levels of d-amphetamine may be related to depletion of catecholamine stores, to replacement by a 'false neurotransmitter' metabolite of amphetamine, or to alteration in receptor sensitivity.

Child

Comparison of radioimmunoassay and gas chromatographic mass spectrometric assay for d-amphetamine.

Quantification of low levels of psychotropic drugs (10(-7) to 10(-9) g ml-1) in small volumes of plasma requires sensitive and accurate methods. Validation of these methods is best achieved by comparing results obtained using several techniques. In this study, amphetamine levels in plasma were measured using gas chromatography mass spectrometry and radioimmunoassay. Correlation of the results obtained by the two methods was found to be positive and high (R = 0.9822). The average coefficient of variation between assays for gas chromatography mass spectrometry was 5.8% and for radioimmunoassay was 12.3%, while the average coefficient of variation within assays for gas chromatography mass spectrometry was 4.9% and for radioimmunoassay 6.9%. Although gas chromatography mass spectrometry was 1.9 times more sensitive than radioimmunoassay, for most purposes, the convenience of the radioimmunoassay method outweights the technical superiority of gas chromatography mass spectrometry.

Animals

Chronic Parkinsonism secondary to intravenous injection of meperidine analogues.

Abuse of 4-propyloxy-4-phenyl-N-methylpiperidine, a meperidine congener, produced parkinsonism in a 23-year-old man. Unlike other drug-induced motor disturbances, the syndrome persisted for 18 months and responded to drugs that stimulate dopamine receptors. Biogenic amines and metabolites in the cerebrospinal fluid and microscopic evaluation of the brain at necropsy were consistent with damage to aminergic neurons in the substantia nigra.

Adult

Effect of moderate exercise on urinary MHPG in depressed patients.

This study attempted to clarify sources of artefact in biochemical studies with affective disorders in which 3-methoxy-4-hydroxy phenylglycol (MHPG) is used as a measurement of change in central nervous system norepinephrine (NE) turnover. Substantial increases in urinary MHPG excretion occurred in ten of the 11 patients when they increased their level of physical activity (0.5 +/- .14 mg/12 hrs versus 1.54 +/- .49 mg/12 hrs). Increases were also observed in NE (19.2 +/- 5.1 microgram/12 hrs versus 25.2 +/- 3.7 microgram/12 hrs). In four patients in whom cerebrospinal fluid MHPG levels were obtained a consistent increase of MHPG levels was observed during the activity period. Elevation of these metabolites were not correlated with changes in depression as reflected by psychiatric observation and rating scales. These data reveal a considerable amount of lability in urinary and CSF MHPG levels in the face of an unchanging affective state. They ask for careful controls for activity and stress in psychiatric patients when urinary MHPG is used as an index of central NE turnover.

Depression

The trial use of clozapine for abnormal involuntary movement disorders.

Twelve patients with abnormal involuntary movement disorders were treated with clozapine in a double-blind, placebo-controlled trial. The cohort consisted of individuals with Gilles de la Tourette's syndrome, Huntington's disease, and atypical persistent dyskinesia that was drug induced. Two subjects were dropped from the protocol due to complications. Two patients with Huntington's disease showed a marked decrease in movements; other individuals obtained no significant therapeutic benefits. Seven of the 10 patients completing the trial experienced moderate or marked side effects.

Adolescent

Catecholamine metabolism in primary anorexia nervosa.

Abnormalities in neuroendocrine function and sympathetic nervous system activity appear to be present in primary anorexia nervosa. Hypothalamic catecholamines are involved in control of endocrine function and norepinephrine is released from sympathetic nerve endings. Because of possible abnormalities in catecholamine metabolism, plasma levels of norepinephrine and urinary excretion of homovanillic acid and 3-methoxy-4-hydroxyphenyl glycol were studied in female patients with primary anorexia nervosa before and after significant clinical improvement and compared with normal female volunteers. During the phase of the disease in which body weights were more than 20--25% below ideal, patients' blood pressures and pulse rates, plasma levels of norepinephrine, and 24-h urinary excretion of 3-methoxy-4-hydroxyphenol glycol and homovanillic acid were lower than those of a group of normal volunteers. After weight gain, these parameters increased to near-normal levels. At no time was plasma dopamine-beta-hydroxylase activity abnormal. The results suggest that abnormalities in catecholamine metabolism in primary anorexia nervosa are caused by starvation, and that neuronal functions dependent on aminergic neurotransmission may be altered as a result.

Adolescent

Hypoxanthine guanine phosphoribosyltransferase (HGPRT) in Gilles de la Tourette syndrome.

Hypoxanthine guanine phosphoribosyltransferase (HGPRT) and adenosine phosphoribosyltransferase (APRT) were examined from 11 individuals with Gilles de la Tourette syndrome, 10 of their first- or second-degree relatives, and 3 normal controls. It has been suggested that in some self-mutilating Tourette patients, HGPRT shows a time-related loss of activity at 4 degrees C, and an unusual isoelectrofocusing pattern. Although 3 patients experienced self-mutilation, no consistent abnormalities were found in the temperature-stability of their HGPRT at 4 degrees C and 70 degrees C, or in isoelectrofocusing of HGPRT purified by immunoprecipitation. An alteration of the purine metabolic pathway in Tourette syndrome has not been established.

Female

Altered gastric emptying and secretion in primary anorexia nervosa.

Primary anorexia nervosa (PAN) is an important psychiatric disease with a 7--21% mortality rate. Although altered gastrointestinal function may be an important aspect of its pathophysiology, no information is available concerning gastric emptying and secretion in those patients. During fasting, fractional emptying rates and hydrogen ion (H+) output were decreased twofold in PAN, as compared with healthy controls, and fluid output was slightly but not significantly decreased. Pentagastrin-induced peak stimulation of H+ output in PAN was 64% of that found in controls (P less than 0.05). Peak gastric fluid output was also significantly less in PAN patients, but suppression of fractional emptying produced by pentagastrin was of the same magnitude in both groups. Following a 250-ml water load, the magnitude and the duration of both the emptying and secretory responses were less in PAN patients than in controls. As a result, the initial increase of intragastric volume was greater in PAN patients than in controls, and the gradual return to fasting volume was delayed in those patients. Follow weight gain, fractional emptying tended to return toward control values, but was still significantly less than in controls following the water load. Gastric H+ and fluid output were not significantly modified following weight gain.

Adult

The circadian variation of catecholamine metabolism in the subhuman primate.

Cerebrospinal fluid (CSF) was removed continuously in 2- or 3-h aliquots from the lateral and fourth cerebral ventricles of chronic chair restrained rhesus monkeys. Under conditions of 12 h light (06.00-18.00 h) and 12 h darkness (18.00-06.00 h) the concentrations of norepinephrine (NE) were found to describe a circadian pattern, with maximal concentrations occurring during the light hours and minimal concentrations occurring during the dark hours. The patterns were generally coincident with the circadian patterns of brain temperature and body activity. When assayed for 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and 3-methoxy-4-hydroxymandelic acid (VMA), samples of CSF collected over 3-4 days demonstrated no reproducible pattern of change. Fluctuation in the concentration of MHPG did not correspond in direction or magnitude to changes in the concentration of VMA. These random fluctuations may in part be accounted for by the influx of the metabolites from peripheral sources to the brain and CSF, and by the relatively slow movement of these metabolites as they diffuse from brain parenchyma to the CSF.

Animals

Probenecid-induced norepinephrine elevations in plasma and CSF.

Probenecid administered in divided oral doses totaling 100 mg/kg increased levels of norepinephrine (NE) in plasma and cerebrospinal fluid (CSF). This technique is commonly used to measure the rate of accumulation of acidic metabolites of certain brain neurotransmitter biogenic amines in CSF after blockade of their transport into blood. Since levels of 3-methoxy-4-hydroxy-phenylethyleneglycol, a neutral metabolite of NE, are also elevated after high oral doses of probenecid, the increases of CSF and plasma NE levels may be directly related to probenecid-induced release of this amine from noradrenergic neurons. In patients who experienced nausea or vomiting there were lower levels of probenecid in CSF, probably secondary to diminished absorption of the medication. These patients also had lower levels of NE in plasma than did patients who remained asymptomatic.

Adolescent

Huntington's dementia. Clinical and neuropsychological features.

The neuropsychiatric syndrome of Huntington's disease is outlined in this report with an emphasis on the cognitive deficits that lend themselves to future neurobehavioral research. Eighteen patients without disabling cognitive or psychiatric symptoms were evaluated for a period of 3 to 15 weeks, with assessment of their cognitive disorder, psychiatric, and neurological symptoms. Neuropsychological examination included repeated mental status examination, the Wechsler Adult Intelligence Scale (WAIS), and, for some, parietal lobe testing. In addition to suffering from a loss of finely detailed memories, patients demonstrated impaired organizing, sequencing, planning, and recalling of information on request. On the WAIS, mean verbal and performance scores were not significantly different. Neuropsychological findings suggested that the Huntington's disease pattern of cognitive impairment is not initially diffuse and homogeneous, but characterized by a relative sparing of several higher cortical functions. Many patients had increased irritability and labile affect. The similarity of Huntington's disease to frontal lobe syndromes is also discussed.

Adult