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Biomedical subjects

M H Ebert

Publications and source records attributed to M H Ebert.

At least 37 records · Page 2Linked to original sources
PubMed1990

Qualitative and quantitative high performance liquid chromatographic analysis of monoamine neurotransmitters and metabolites in cerebrospinal fluid and brain tissue using reductive electrochemical detection.

The application of reductive coulometric electrochemical detection for analysis of the monoamine neurotransmitters norepinephrine, dopamine, and serotonin and their common metabolites in brain and cerebrospinal fluid following separation by isocratic high performance liquid chromatography is described. The high sensitivity and screening capabilities of coulometric electrodes permits the accurate quantitation of as little as 3-5 pg of these compounds in tissue following a simple single step purification procedure. Moreover, comparison of peak height ratios obtained from analysis of authentic reference standards and tissue samples at selected multiple electrode potentials provides a straightforward means for qualitative evaluation of peak identification and purity during analysis of biological samples. The method is comparatively inexpensive and precise within and between day coefficients of variation for most compounds range from 2-5%. Thirty samples can be run in duplicate in a 24 h period.

Animals↗
PubMed1990

Isoproterenol infusion test in anorexia nervosa: assessment of pre- and post-beta-noradrenergic receptor activity.

Anorexia nervosa is associated with alterations in sympathetic activity and metabolism that persist during and after weight recovery. This study assessed beta-adrenergic receptor activity, an important modulator of vascular and metabolic function, in anorexic patients studied when underweight and at intervals during recovery, in comparison with healthy volunteer women. An increase in heart rate, in response to increasing doses of isoproterenol, served as an index of postsynaptic activity. Anorexic patients, during refeeding and weight gain, needed a significantly higher dose of isoproterenol to increase basal heart rate by 25 beats/minute, compared with underweight anorexic patients. Down-regulated postsynaptic cardiac beta-adrenoceptors during weight gain may protect against refeeding-induced exaggerated sympathetic activity. Because presynaptic beta-adrenoceptors serve as a positive feedback loop for synaptic catecholamine secretion, the increase in plasma norepinephrine concentrations during the isoproterenol infusion served as an index of presynaptic activity. We found that increasing doses of isoproterenol were associated with a linear increase in plasma norepinephrine in each healthy volunteer. In contrast, anorexic patients at any state had a significantly more erratic secretion of plasma norepinephrine in response to increasing doses of isoproterenol. Altered regulation of presynaptic adrenoceptors may explain, in part, the large variance and little consensus between previous studies as to whether anorexic patients have reduced or normal plasma norepinephrine levels.

Anorexia Nervosa↗
PubMed1989

Central and peripheral ACTH and cortisol levels in anorexia nervosa and bulimia.

To explore the relationship of central and peripheral adrenocorticotropic hormone (ACTH, or corticotropin) levels to hypothalamo-pituitary-adrenal axis dysfunction in patients with eating disorders, levels of cerebrospinal fluid (CSF) and plasma ACTH, cortisol, and 24-hour urinary free cortisol were measured in 16 patients with anorexia nervosa (60% +/- 1.1% of ideal body weight), 14 patients with bulimia (93.2% +/- 4.6% of ideal body weight), and 11 healthy age-matched women volunteers. The CSF, plasma, and urinary free cortisol levels were elevated in underweight anorexic patients and showed declines following weight recovery. Cortisol-binding globulin levels were similar in anorexics and controls. In contrast, underweight anorexics showed low CSF ACTH levels that returned to normal following weight recovery, and their plasma ACTH levels were normal. On hospital admission, bulimic patients demonstrated normal ACTH and cortisol levels. After their abstinence from binge-purge episodes, the CSF ACTH levels decreased significantly. Positive relationships were found among CSF, plasma, and urinary cortisol levels, and inverse relationships were seen between cortisol measures and CSF ACTH levels in patients with eating disorders. Secretion of ACTH into the CSF may respond to feedback by cortisol or, alternatively, may be suppressed by the hypersecretion of corticotropin-releasing hormone, leading to the depletion of the pro-opiomelanocortin molecule.

Adolescent↗
PubMed1989

A longitudinal study of the effect of different social rearing conditions on cerebrospinal fluid norepinephrine and biogenic amine metabolites in rhesus monkeys.

The purpose of this study was to determine whether disruption of early social attachment alters the activity of brain biogenic amine systems in rhesus monkeys (Macaca mulatta). Male rhesus monkey infants were deprived of maternal interaction, peer interaction, or both, during the first 22 months of life. Cerebrospinal fluid (CSF) was collected under rigorously controlled conditions approximately every month and assayed for levels of norepinephrine (NE), its major metabolite, and the metabolites of dopamine and serotonin. Mother-Deprived infants had lower levels of CSF NE than Mother-Reared infants. Mother-Deprived infants also failed to develop the same pattern of intercorrelations between compounds and month-to-month stability in levels of neurotransmitter and metabolites in CSF as the Mother-Reared infants. Finally, there were changes in CSF NE levels associated with social separation and social group formation. The brain NE system appears to be sensitive to changes in the social environment. Its level of activity, as reflected in levels of NE in CSF, appears to depend on both the prevailing social environment and the prior rearing environment.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Decreased caloric intake in normal-weight patients with bulimia: comparison with female volunteers.

Patients with bulimia (binge-purge syndrome) frequently complain that they consume a very restrictive diet to avoid gaining weight. To investigate this claim, 23 hospitalized bulimic patients were assessed daily for body weight, caloric intake, macronutrient diet content, activity measures, and body composition estimates during weight-stable periods. Bulimic patients ate fewer kilocalories per kilogram body weight (22.1 +/- 4.6 kcal/kg) than did age-matched normal women (29.7 +/- 6.5 kcal/kg) but had similar activity levels and body composition. Clinical variables, such as history of laxative abuse, anorexia, or obesity, and physiological characteristics, such as body weight, activity level, or dietary content, could not account for this difference in caloric consumption. Bulimic patients tended to eat a diet lower in fat and higher in protein than did control subjects. These results agree with observations of increased efficiency of caloric utilization in obese patients and support patient complaints of a tendency to gain weight easily.

Adolescent↗
PubMed1989

Contribution of CNS neuropeptide (NPY, CRH, and beta-endorphin) alterations to psychophysiological abnormalities in anorexia nervosa.

Patients with anorexia nervosa have neuroendocrine and behavioral alterations that starvation and weight loss are thought to cause, or contribute to, since they are reversed by weight restoration. We have found that anorexics have starvation-related disturbances of neuropeptide Y (NPY), corticotropin-releasing hormone (CRH), and beta-endorphin, as determined by their measurements in cerebrospinal fluid. The relationship between these neuropeptides and several symptoms in anorexia, together with findings in experimental animals, raise a possibility that changes in the activity of these neuropeptides contribute to neuroendocrine and behavioral alterations in anorexia. Specifically, a disturbance of central nervous system CRH activity is likely to be responsible for hypercortisolemia, while a disturbance of central nervous system NPY may contribute to amenorrhea. In addition, disturbances of these neuropeptides could contribute to other symptoms such as increased physical activity, hypotension, reduced sexual interest, depression, and pathological feeding behavior.

Adult↗
PubMed1987

Reduced cerebrospinal fluid levels of immunoreactive pro-opiomelanocortin related peptides (including beta-endorphin) in anorexia nervosa.

The discovery that the endogenous opioid peptides contribute to the modulation of appetitive behavior and neuroendocrine function has raised questions as to whether disturbances of opioids contributes to the pathophysiology of eating disorders. To assess central nervous system (CNS) beta-endorphin in patients with anorexia nervosa we measured cerebrospinal fluid (CSF) beta-endorphin concentrations before, and at intervals after weight correction. In addition, we measured three sister peptides (beta-lipotropin, adrenocorticotropic hormone (ACTH), and the N-terminal fragment) derived from the same precursor molecule, pro-opiomelanocortin (POMC) to determine whether possible disturbances might extend to sister peptides. Underweight anorectics (58 +/- 5% of average body weight (ABW), n = 10) had significantly lower CSF concentrations of all 4 peptides compared to healthy controls (102 +/- 10% ABW, n = 11). CSF concentrations of all 4 POMC-related peptides were found to be significantly increased when the same anorectics were restudied 4 to 6 weeks after weight gain (83 +/- 4% ABW). After weight gain, levels of CSF beta-endorphin, beta-lipotropin, and ACTH were similar to controls, whereas levels of CSF N-POMC remained significantly less than controls. Another group of women, previously underweight with anorexia nervosa, but weight-restored (93 +/- 11% ABW, n = 12) for greater than 1 year had CSF concentrations of all 4 POMC-related peptides that were similar to controls. We conclude that underweight anorectics have state-associated disturbances of CNS beta-endorphin as well as other POMC-related peptides. These abnormalities are part of the neurobiological syndrome of anorexia nervosa and may contribute to the characteristic alterations in behavior and neuroendocrine function.

Adrenocorticotropic Hormone↗
PubMed1987

Elevated cerebrospinal fluid levels of immunoreactive corticotropin-releasing hormone in anorexia nervosa: relation to state of nutrition, adrenal function, and intensity of depression.

To study the pathophysiology of hypercortisolism in anorexia nervosa, we measured the cerebrospinal fluid (CSF) levels of corticotropin-releasing hormone (CRH) in patients when they were underweight and at intervals after weight restoration. CSF CRH levels were significantly elevated in hypercortisolemic underweight patients. Both CSF CRH levels and pituitary-adrenal function normalized after weight recovery. A significant positive correlation was found between CSF CRH levels and depression ratings in weight-corrected patients. We conclude that the hypercortisolism of anorexia nervosa reflects a defect at or above the hypothalamus which results in the hypersecretion of endogenous CRH. The positive correlation between CSF CRH and depression in the weight-restored patients is compatible with previous data indicating increased CRH secretion in the depressed phase of primary affective disorder and supports the notion of a relationship between CRH and depressive symptomatology. Moreover, these data are compatible with observations that depression is part of the anorexia nervosa syndrome.

Adrenal Glands↗
PubMed1986

Caloric intake necessary for weight maintenance in anorexia nervosa: nonbulimics require greater caloric intake than bulimics.

In the past decade, patients with anorexia nervosa have been subdivided by the presence or absence of binging-and-purging behavior. Psychologic, physiologic, and premorbid weight differences have also been discovered between these subgroups. We now report that nonbulimic anorectics required 30-50% more caloric intake than bulimic anorectics to maintain a stable weight. This difference in caloric intake was independent of phase of illness; it was present at low weight and at intervals after weight restoration. Subjects were closely supervised on an inpatient hospital ward so that they could not binge or purge. Motor activity did not appear to explain these alterations in caloric requirements. Such differences in caloric intake could be trait related or a consequence of many years of starving or binging behavior. These findings are clinically relevant for advising eating disorder patients of caloric requirements necessary to maintain a normal weight.

Adult↗
PubMed1986

Sleep EEG in Korsakoff's psychosis and Alzheimer's disease.

All-night sleep EEGs were compared in the following age-equivalent groups: seven men with Korsakoff's psychosis (KP), six men and two women with presumptive Alzheimer's disease, and six healthy men and three healthy women. KP patients had significantly increased intermittent time awake than both controls and Alzheimer patients, and shorter REM latency minus time awake than controls. Alzheimer patients had significantly reduced delta sleep than controls. Differences in the pattern of sleep EEG abnormalities may be due to different pathogenic mechanisms, but their utility in differential diagnosis requires further study.

Aged↗
PubMed1985

The clinical syndrome of striatal dopamine deficiency. Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a syndrome that resembles Parkinson's disease. To compare the biochemical abnormalities produced by this compound in human beings with those occurring in Parkinson's disease, we examined biogenic amine metabolites in cerebrospinal fluid and urine from six patients with MPTP-induced parkinsonism and eight patients with Parkinson's disease. In both forms of parkinsonism, the cerebrospinal fluid levels of homovanillic acid, the major metabolite of dopamine, were reduced, whereas the levels of the serotonin metabolite 5-hydroxyindoleacetic acid were normal. The cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the major metabolite of norepinephrine in the brain, after adjustment for plasma MHPG, were elevated (greater than 6.0 ng per milliliter) in MPTP-induced parkinsonism, whereas MHPG levels were reduced (less than 6.0) in Parkinson's disease. Neurons containing norepinephrine in the brain are involved in the degenerative process of Parkinson's disease, whereas they are spared in MPTP-induced parkinsonism. The selective destruction by MPTP of nigrostriatal dopamine neurons that is responsible for the movement disorder also appears to result in an increase in central noradrenergic activity, which is not possible in Parkinson's disease. Thus, differences in central noradrenergic activity, reflected in cerebrospinal fluid levels of MHPG, distinguish these two forms of parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Effects of alcohol on cerebrospinal fluid norepinephrine in rhesus monkeys.

Alcohol (1-3 g/kg) significantly increased the concentration of cerebrospinal fluid (CSF) norepinephrine (NE) in rhesus monkeys. This effect is consistent with the previously demonstrated activational and possible antidepressant effect of low doses of alcohol. The greatest increase was observed in subjects with low baseline levels of CSF NE. Individual differences in activation or euphoria could be related to differential increases in CSF NE following alcohol consumption.

Alcohol Drinking↗
PubMed1985

Altered norepinephrine metabolism following long-term weight recovery in patients with anorexia nervosa.

This study evaluated the relationship between noradrenergic function and long-term weight recovery in patients with anorexia nervosa. Eleven patients with long-term weight maintenance (6 to 72 months) had lower plasma and cerebrospinal fluid concentrations of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol than did healthy controls. Reduced noradrenergic activity may be associated with long-term stability of weight recovery in patients with anorexia nervosa.

Adolescent↗
PubMed1984

Abnormalities in CNS monoamine metabolism in anorexia nervosa.

Patients with anorexia nervosa have disturbances of mood, appetite, and neuroendocrine function. Central nervous system monoamine pathways modulate these systems, and alterations in function of these systems may occur in anorexia nervosa. Because monoamine metabolism can be influenced by nutritional intake, we studied anorectics before and at intervals after correction of weight loss. Underweight anorectics had a 30% decrease in CSF homovanillic acid level and a 20% decrease in CSF 5-hydroxyindoleacetic acid concentration; these values returned to normal shortly after weight recovery. The CSF level of norepinephrine (NE) in underweight anorectics and in these patients a few weeks after weight restoration was similar to that in normal subjects. Long-term weight-recovered (20 +/- 7 months) anorectics, however, had a 50% decrease in CSF NE level compared with that of controls. Underweight anorectics have state-associated disturbances in dopamine and serotonin metabolism. Changes in NE metabolism are more complex and state independent. These abnormalities in neurotransmitter metabolism are part of the neurobiological syndrome of anorexia nervosa and may contribute to the characteristic changes in mood, behavior, and neuroendocrine function.

Adolescent↗