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Biomedical subjects

M Levitt

Publications and source records attributed to M Levitt.

At least 163 records · Page 9Linked to original sources

Apparent turnover of norepinephrine in the intact rat brain estimated from its rate of appearance in the cerebroventricular compartment.

The apparent turnover of norepinephrine (NE) in the intact brain of urethane-anesthetized rats was estimated in vivo from the rate of appearance of endogenous NE in the cerebroventricular compartment. Ventriculocisternal perfusion, a radioenzymatic assay for endogenous NE and isotope dilution of 3H-NE were used to determine the rate of appearance (Ra) of NE. The effect of tranylcypromine, a monoamine oxidase (MAO) inhibitor and releasing agent on Ra of NE, was also studied. In control animals, the mean Ra value was 0.40 pmol/min. Pretreatment with tranylcypromine resulted in a threefold increase in the mean value for Ra, which was due to increased secretion of NE into the CSF. The results indicate that 90% of the NE entering the cerebroventricular compartment was removed. Pretreatment with tranylcypromine did not modify removal, thus suggesting that tranylcypromine has no effect on the physiological processes which regulate the removal of NE from the CSF.

Animals↗

Fate of tritium derived from prenatally administered tritiated methadone in dams and neonatal rats.

Tritiated methadone (3HME) was administered to gravid rats on the last week of gestation, fostered neonates periodically sacrificed, and brain and liver tritium determined by combustion. Concentrations of tritium were highest in brain on the day of birth and declined rapidly so that after 5 days, 20% remained, and after 25 days, 2% remained; similar values were found in liver. In maternal brain, concentrations on the day of birth were essentially the same as offspring brain. The brain concentrations of methadone are discussed in relation to neurobehavioral effects.

Animals↗

Measurement of tritiated norepinephrine metabolism in intact rat brain.

A procedure for the study of NE metabolism in the intact rat brain is described. The method involves ventriculocisternal perfusion of the adult male rat with artificial CSF containing [3H]NE. Radioactivity in the perfusate associated with NE and its metabolites 3,4-dihydroxymandelic acid (DOMA), 3,4-dihydroxyphenylethyleneglycol (DHPG), 3-methoxy-4-hydroxymandelic acid (VMA), 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), and normetanephrine (NMN) is separated using high-performance liquid chromatography (HPLC). After 80 min the radioactivity in the perfusate reaches an apparent steady-state. Analysis of the steady-state samples shows higher activity in the fractions corresponding to DHPG and MHPG than in those corresponding to DOMA and VMA, confirming glycol formation as the major pathway of NE metabolism in rat brain. Pretreatment with an MAO inhibitor (tranylcypromine) results in a marked decrease in the deaminated metabolites DHPG and MHPG and a concurrent increase in NMN. The results indicate this to be a sensitive procedure for the in vivo determination of changes in NE metabolism.

Animals↗

The bilaterally symmetrical deafferentation syndrome in macaques after bilateral spinal lesions: evidence for dysesthesias resulting from brain foci and considerations of spinal pain pathways.

Six macaques had been subjected to chronic left thoracic anterolateral cordotomy, which released persistent self-attacks of the hypoalgesic right hind limb. One to 4 weeks later, lesions were placed in the right thoracic spinal cord, 2-5 segments apart from the left lesion. None of these second-stage spinal lesions, including spinal hemisection, affected the continued self-attacks of the right leg. Therefore, the chronic deafferentation syndrome of contralateral anterolateral cordotomy is not dependent upon the rostral conduction, via long spinal sensory tracts, of neural activity from ipsilateral lumbosacral spinal segments. Furthermore, second-stage right thoracic spinal lesions, which damaged the anterolateral tracts in 4 macaques, caused the release of the deafferentation syndrome in the left hind limb, despite extensive prior destruction of the left anterolateral tracts. Therefore, the release of the deafferentation syndrome by contralateral cordotomy is independent of the functional activity of the ipsilateral anterolateral tracts. The bilateral symmetry of this syndrome after extensive bilateral spinal lesions suggests pathophysiological foci at the level of the brain rather than the spinal cord. This syndrome is considered to be an objective index of disturbing subjective sensations.

Animals↗

Phase II trial of aziridinylbenzoquinone (AZQ) in patients with refractory small cell carcinoma of the lung.

Sixteen previously treated patients received AZQ in a phase II study to test therapeutic efficacy in refractory small cell lung cancer. The dose and schedule of AZQ was 20 mg/m2 day 1 and 8, with treatments repeated every 28 days. No objective responses were noted among 16 evaluable patients. Myelosuppression was the major toxicity. AZQ does not appear to have antitumor activity in patients with previously treated small cell carcinoma.

Adult↗

Energy expenditure in obesity in fasting and postprandial state.

Resting metabolic rate (RMR) was determined in 10 obese and 10 nonobese women after an overnight fast and for 3 h after the ingestion of an 800-kcal liquid meal. In the fasting state, absolute energy expenditure in the obese (4.8 +/- 0.2 kJ/min) was 25% greater than in the nonobese (P less than 0.005), but was comparable with the nonobese when expressed in relation to body surface area or lean body mass and was reduced by 20% when expressed per kilogram body weight3/4 (P less than 0.005). Meal ingestion resulted in a 14-16% increase in RMR (postprandial thermogenesis) that was similar in the two groups, so that absolute energy expenditure in the obese remained 22-25% higher than in the nonobese throughout the postprandial period. The estimated overall (fasting and postprandial) increase in resting caloric expenditure in the obese as compared with the nonobese was 350-375 kcal/day.

Adult↗

Platelet monoamine oxidase and plasma amine oxidase: effect of anticoagulant and centrifugation technique on platelet yield and enzyme activity.

Platelet recovery and activity of platelet monoamine oxidase (MAO) and plasma amine oxidase (PAO) were determined using different centrifugation procedures (125 g for 15 min vs. 600 g for 2.5 min) and anticoagulants. With either centrifugation procedure, the use of ethylenediaminetetraacetate (EDTA) as anticoagulant resulted in higher platelet yields and MAO activity compared to acid-citrate-dextrose (ACD). However, PAO activity was lower with EDTA as anticoagulant than with ACD. There was a trend toward higher platelet yields and higher activity levels of MAO and PAO with the 125 g centrifugation method than with the 600 g technique regardless of the anticoagulant used. The implications for MAO studies in psychiatric research were discussed.

Adult↗

Randomized study of cyclophosphamide, doxorubicin, and etoposide (VP16-213) with or without cisplatinum in non-small cell lung cancer.

Sixty-eight patients with non-small cell lung cancer were treated in a prospectively randomized study with cyclophosphamide, doxorubicin (Adriamycin), and etoposide (VP16-213) with cisplatinum (CAE +/- P). Response rate, time to progression, and survival of CAE-P treated patients were each superior compared to those of patients who received CAE therapy. Of 36 patients, 10 (4 complete remissions, 6 partial remissions) responded to CAE-P and of 29 patients 3 (1 complete remission, 2 partial remissions) responded to CAE (p = 0.073). The median time to treatment failure was 22.9 wk for the CAE-P regimen and 15.0 wk for CAE (p = 0.032). The median survival for patients treated on the regimen with and without cisplatinum was 34.5 and 22.5 wk, respectively (p = 0.04). There were two CAE-P and one CAE drug-related deaths. Toxic effects were more severe in the CAE-P regimen. The addition of cisplatinum to the CAE combination produced an increase in response rate with significant prolongation in both time to progression and survival, but did add morbidity. These results suggest that the combined use of cisplatinum with at least one of the chemotherapeutic agents in the CAE regimen is synergistic.

Adenocarcinoma↗

Hypernatremia induced by maximal exercise.

A short burst of intensive exercise (100-m swim lasting one minute and resulting in a 12-fold rise in the level of blood lactate) resulted in frank hypernatremia (serum sodium level, greater than 150 mEq/L) in 30% to 40% of well-trained athletes. In contrast, less intensive exercise (800-m swim lasting ten minutes and resulting in a sevenfold rise in the level of blood lactate) failed to cause a rise in serum sodium level despite comparable elevations in hematocrit reading and serum protein levels. Hypernatremia induced by intensive exercise cannot be explained by losses in body fluid or solute ingestion, but is probably a consequence of a shift of hypotonic fluid from the extracellular to the intracellular compartment. Thus, the mechanism of exercise-induced hypernatremia may be unique, as compared with other clinically recognized forms of hypernatremia.

Adolescent↗

Neuroleptic drug effect on platelet monoamine oxidase and plasma amine oxidase in schizophrenia.

Activity levels of platelet monoamine oxidase (MAO) and plasma amine oxidase (PAO) were determined in eight chronic schizophrenic patients who had been treated with neuroleptic drugs for 3 months. The mean reduction in platelet MAO activity was 18.6%. The extent of decrease was statistically significant. The reduction in enzyme activity was unrelated to serum iron levels. PAO activity was unaltered. The implications for schizophrenia research are discussed.

Adult↗

Assay of human erythrocyte catechol-o-methyltransferase activity with naturally occurring catecholamines as substrates.

This report describes a simple and sensitive radiometric assay for catechol-o-methyltransferase activity in human erythrocytes and other tissues. Saturating concentrations of the endogenous catecholamines and S-adenosylmethionine are used under optimum assay conditions. Erythrocyte catechol-o-methyltransferase activity is also dependent on storage conditions, as activity was lost at -20 degrees C but not at -80 degrees C.

Catechol O-Methyltransferase↗

Neuroleptic drug effect on plasma dopamine-beta-hydroxylase in schizophrenia.

Plasma dopamine-beta-hydroxylase (DBH) activity was determined in 8 chronic schizophrenic patients following neuroleptic treatment for 2 months. Enzyme activity was decreased by 13.7 +/- 3.4% (mean +/- SD). The difference from pre-drug levels was not statistically significant. The reduction in DBH activity stabilized after the 1st month of treatment and was unrelated to neuroleptic drug load.

Adult↗