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Biomedical subjects

T B Cooper

Publications and source records attributed to T B Cooper.

At least 145 records · Page 8Linked to original sources
PubMed1989

Serotonergic studies in patients with affective and personality disorders. Correlates with suicidal and impulsive aggressive behavior.

Dysfunction of the central serotonergic system has been variously associated with depression and with suicidal and/or impulsive aggressive behavior. To evaluate central serotonergic function in relation to these variables, prolactin responses to a single-dose challenge with fenfluramine hydrochloride (60 mg orally), a serotonin releasing/uptake-inhibiting agent, were examined in 45 male patients with clearly defined major affective (n = 25) and/or personality disorder (n = 20) and in 18 normal male control patients. Prolactin responses to fenfluramine among all patients were reduced compared with responses of controls. Reduced prolactin responses to fenfluramine were correlated with history of suicide attempt in all patients but with clinician and self-reported ratings of impulsive aggression in patients with personality disorder only; there was no correlation with depression. These results suggest that reduced central serotonergic function is present in a subgroup of patients with major affective and/or personality disorder and is associated with history of suicide attempt in patients with either disorder, but with impulsive aggression in patients with personality disorder only.

Adult↗
PubMed1989

A placebo-controlled comparison of nortriptyline and phenelzine in maintenance therapy of elderly depressed patients.

Fifty-one elderly depressed outpatients who had responded to antidepressants and completed continuation therapy were observed under double-blind conditions for 1 year. Twenty-three had been switched to placebo, while 13 and 15 took nortriptyline hydrochloride and phenelzine sulfate, respectively. Patients administered phenelzine did significantly better with 13.3% recurrences than patients administered either nortriptyline (53.8% recurrences) or placebo (65.2% recurrences). In addition, patients who had higher Hamilton scores and who had an earlier age of onset of the first depressive episode were significantly more likely to have recurrences.

Aged↗
PubMed1989

Direct radioimmunoassay procedure for plasma dexamethasone with a sensitivity at the picogram level.

A simple radioimmunoassay (RIA) for the direct quantitation of plasma dexamethasone (DEX) at the picogram level has been developed. An antiserum with high specificity and avidity was obtained by the immunization of a carefully synthesized dexamethasone-21-succinyl-thyroglobulin with a high incorporation ratio. As little as 1 pg of DEX in 50 microL of plasma sample can be detected directly by this RIA without extraction and other purification procedures. Intra- and interassay coefficients of variation were 2.1 and 3.3% for plasma levels at 2.93 ng/mL or 2.3 and 7.2% for plasma levels at 0.88 ng/mL. Blank values for plasma of normal or pre-DEX patients were always under the detection limit (20 pg/mL). Excellent linearity (r = 0.9991-0.9999) was demonstrated between the serial dilutions of six plasma samples and their corresponding DEX concentrations. In single-dose DEX (0.25-1 mg) pharmacokinetic studies, plasma DEX was consistently detectable up to 24 h post dose. Compared with existing methods, this direct RIA demonstrates superior performance with regard to simplicity, sensitivity, specificity, and reproducibility. It also enables high sample throughput and has proven robust in our hands. This assay should be readily transferable to other laboratories for clinical or research purposes.

Animals↗
PubMed1989

Plasma levels of nortriptyline and 10-hydroxynortriptyline and treatment-related electrocardiographic changes in the elderly depressed.

Thirty-one elderly depressed patients were treated for seven weeks with nortriptyline with plasma levels kept between 50-180 ng/ml. Electrocardiograms were taken at the third and seventh weeks of treatment. There were significant increases in the PR interval, QTc interval, and heart rate from before and after treatment. However, there were no consistent correlations between electrocardiographic changes during treatment and plasma levels of nortriptyline, 10-hydroxynortriptyline and either of its two isomers (E-10-hydroxynortriptyline, Z-10-hydroxynortriptyline). Increased QRS duration after seven weeks of treatment was correlated with daily dose of nortriptyline.

Aged↗
PubMed1989

Factors affecting the delay of antidepressant effect in responders to nortriptyline and phenelzine.

Seventy-six elderly depressed patients who had responded to either nortriptyline or phenelzine after a trial of up to 3 months were examined. The mean week of response was nearly 6 weeks. Patients who were more severely depressed took longer to respond. Patients with endogenous depression responded sooner on nortriptyline than did patients with nonendogenous depression. For patients on nortriptyline, lower plasma levels in the early weeks of treatment may delay response while differences in platelet monoamine oxidase inhibition in the early weeks of treatment do not appear to affect week of response for patients on phenelzine.

Aged↗
PubMed1989

Differential effects of methylphenidate and dextroamphetamine on the motor activity level of hyperactive children.

An acceleration-sensitive device was used to measure motor activity continuously through the day in 18 hyperactive boys in a day hospital program. The children received methylphenidate, dextroamphetamine, or placebo daily after breakfast and lunch in an 11-week double-blind crossover trial. Differential effectiveness of the two drugs in lowering motor activity was found. Methylphenidate significantly lowered activity measurements in a morning structured classroom and in less structured activities in the afternoon. Dextroamphetamine effects on activity were similar, although they did not differ significantly from placebo effects between 11:00 AM and noon in our classroom setting. Methylphenidate produced a greater decrement in motor activity than did dextroamphetamine between 11:00 AM and 1:00 PM. There were no significant differences in activity level between drug doses within each drug phase across the dose ranges used (for methylphenidate 0.45 to 1.25 mg/kg given twice daily, and for dextroamphetamine 0.2 to 0.6 mg/kg given twice daily). Plasma drug concentrations did not correlate with decrements in activity for either drug.

Child↗
PubMed1989

Sustained release methylphenidate: pharmacokinetic studies in ADDH males.

Methylphenidate is widely used in the treatment of school-age children with attention deficit disorder with hyperactivity (ADDH). It is available in a short-acting (MPH) and a long-acting (MPH-SR) preparation. Nine males with ADDH participated in a 1-day pharmacokinetic study following a single morning dose of 20 mg. MPH-SR. Data are presented on MPH-SR's half-life (T 1/2), peak concentrations achieved (Cmax) and the time to the peak plasma concentrations (Tmax). Similar data were gathered from a second group of eight ADDH males treated with a higher, single morning dose of standard, short-acting MPH. After adjusting for dose differences, comparisons of the two sets of plasma concentration curves suggest that MPH-SR has a longer Tmax, but that it does not reach the same Cmax as an identical dose of standard MPH.

Adolescent↗
PubMed1989

Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia.

Because CNS neuroleptic concentration cannot be directly measured in patients, the relation between clinical response and extent of dopamine receptor blockade is unknown. This relationship is critical in ascertaining whether nonresponse to neuroleptics is the result merely of inadequate CNS drug levels or of more basic biological differences in pathophysiology. Using [18F]N-methylspiroperidol and positron emission tomography, the authors assessed dopamine receptor occupancy in 10 schizophrenic patients before and after treatment with haloperidol. Responders and nonresponders had virtually identical indices of [18F]N-methylspiroperidol uptake after treatment, indicating that failure to respond clinically was not a function of neuroleptic uptake or binding in the CNS.

Adolescent↗
PubMed1989

10-Hydroxynortriptyline and treatment effects in elderly depressed patients.

Sixty-four elderly depressed outpatients were treated with nortriptyline for seven weeks. Plasma nortriptyline and its main metabolite, 10-hydroxynortriptyline, were measured weekly. No relationship was found between levels of 10-hydroxynortriptyline and clinical response. Plasma levels of the trans isomer, E-10-hydroxynortriptyline, were significantly lower when dizziness and symptoms of orthostatic hypotension were reported, although there was no significant correlation with actual orthostatic drop in systolic pressure. Plasma level of 10-hydroxynortriptyline was not significantly correlated with the other reported side effects.

Aged↗
PubMed1989

Pharmacokinetics of desipramine in Asian and Caucasian volunteers.

The pharmacokinetic differences of tricyclic antidepressants (TCAs) in Asians and Caucasians remain controversial. Thirty-seven age-matched healthy volunteers (18 Asians and 19 Caucasians) ingested a single desipramine (DMI) dose of 1.0 mg/kg of body weight. Blood was obtained at 1, 3, 5, 7, 12, 24, 48, 72, and 96 hours after dosing. Serial 24-hour urine samples were collected for 5 days. There were no statistically significant differences in plasma levels between the two groups. DMI concentrations peaked a median of 5 hours after ingestion in Asians vs. 3 hours in Caucasians. Total clearances of DMI (CL DMI) and hydroxylated DMI (OH-DMI) were greater in Caucasians. These differences were no longer significant when corrected for body weight. Clearances appeared to follow tri-modal distributions. The proportions of Asians and Caucasians falling into the slow, intermediate, and rapid clearance groups were not significantly different, but there was a tendency for more Caucasians to be in the rapid clearance group.

Adult↗
PubMed1988

Formation of fatty acid ethyl esters during chronic ethanol treatment in mice.

Ethyl esters of long-chain fatty acids are formed in the liver and brain of mice after 1-6 days of ethanol intoxication. This observation extends the reports of Lange and co-workers who detected these compounds as unusual metabolites of ethanol in human tissues [E. A. Laposata and L. G. Lange, Science 231, 497 (1986)]. Ethyl esters of oleic and linoleic acids, and, in smaller amounts, ethyl esters of palmitic and stearic acids were found in the livers of mice that had been treated with ethanol by inhalation. In the brain, only the esters of unsaturated fatty acids were found, in lower amounts than in liver. All the fatty acid ethyl esters seemed to have reached steady-state levels in the tissues after 3 or 4 days of alcohol treatment. When incorporated into synaptosomal plasma membranes in vitro, in intramembrane concentrations estimated to resemble those observed in the mice, these esters reduced the fluorescence anisotropy, i.e. they disordered the membranes.

Alcoholism↗
PubMed1988

Isolation and identification of the glucuronide conjugate of 2-hydroxydesipramine by preparative liquid chromatography.

A semi-preparative column liquid chromatographic procedure for the isolation and purification of milligram quantities of the glucuronide conjugate of 2-hydroxydesipramine, a major metabolite of desipramine, is presented. Urine from patients receiving desipramine was collected and passed through a column of XAD-2 resin. The methanolic extract was chromatographed on a reversed-phase octadecyl semi-preparative column followed by further purification on a silica gel column of the same dimension, yielding a product 95% pure. Fast atom bombardment and thermospray mass spectroscopy, as well as ultraviolet photodiode-array spectroscopy and hydrolysis with beta-glucuronidase confirmed the identification and purity of 2-hydroxydesipramine glucuronide. This important glucuronide metabolite will be a useful tool as an authentic standard for pharmacokinetic and metabolism studies and for determining its pharmacological characteristics in laboratory animals.

Chromatography, High Pressure Liquid↗
PubMed1988

Heavy smokers, smoking cessation, and clonidine. Results of a double-blind, randomized trial.

Seventy-one heavy smokers who had failed in previous attempts to stop smoking participated in a randomized clinical trial to test the efficacy of clonidine as an aid in smoking cessation. The success rate in clonidine-treated subjects (verified by serum cotinine concentration) was more than twice that in the placebo-treated subjects. When the data were stratified by gender, a strong effect present in women was not apparent in men. After six months, cessation rates remained significantly higher among smokers treated with clonidine than those receiving placebo. The data also revealed an unexpectedly high prevalence (61%) of a history of major depression in this sample and a significant negative effect of such a history on cessation regardless of treatment. These findings, highly suggestive of an important role of clonidine in smoking cessation, warrant further studies to establish the long-term (greater than or equal to 12 months) efficacy of this drug and to replicate the association between nicotine dependence and depression.

Adolescent↗
PubMed1988

How effective and safe is continuation therapy in elderly depressed patients? Factors affecting relapse rate.

Sixty elderly depressed patients who had responded to either nortriptyline hydrochloride or phenelzine sulfate were followed up under double-blind conditions during four to eight months of continuation treatment. Over 70% of patients (43) remained well during this period, while 11 (18.3%) had relapses, three (5.0%) dropped out because of side effects, and three (5.0%) prematurely terminated in good clinical condition. There was no significant difference in the relapse rate between patients receiving nortriptyline (five [16.7%]) and those receiving phenelzine (six [20.0%]). Patients receiving phenelzine were more likely to require dose reductions, and all three patients who dropped out because of side effects were receiving phenelzine. Patients with chronic depression (greater than two years' duration) accounted for all of the relapses.

Age Factors↗
PubMed1988

A highly sensitive and specific radioimmunoassay for quantitation of plasma fluphenazine.

Antisera of high sensitivity and selectivity were obtained from rabbits immunized with conjugates of hemisuccinylated fluphenazine and porcine thyroglobulin. The antiserum selected (titer 1:6000) for the development of the RIA was obtained after a priming dose and a single iv booster injection three months later. This antiserum had negligible crossreactivity with known available metabolites of fluphenazine (FPZ) and an affinity constant of 2 X 10(10) L/mol. Tritiated FPZ was further purified by HPLC and used as a ligand. The method detects as little as 20 pg/mL of plasma (4 pg/RIA tube) after 1 mL of plasma is extracted. The extraction was performed at a basic pH with heptane: isoamyl alcohol (99:1); the solvent was then back extracted using an acetic phosphate buffer. Recoveries were uniformly high (88.6 +/- 2.1%), and this aqueous buffer extract was used directly in the RIA procedure. The assay has intra- and interassay coefficients of variation of 5.8 and 8.2%, respectively, in a plasma concentration of 95 pg/mL. Results using this procedure have been cross validated against an HPLC procedure (r = 0.952, slope = 1.032, intercept = 0.009, n = 18). In a single-dose FPZ study (10 mg, po), plasma FPZ levels in 25 normal volunteers could be monitored greater than 48 h post dose. Single plasma level profiles, after an initial injection of 12.5 mg of FPZ decanoate, could be measured greater than 36 d, and, in some cases, up to 100 d post dose.

Administration, Oral↗
PubMed1988

Response of the melatonin cycle to phototherapy for Seasonal Affective Disorder. Short note.

It is well-established that human nocturnal melatonin secretion is suppressed by presentation of artificial light greater than 2,000 lux, a level that is also therapeutically effective in alleviating winter depression symptoms of Seasonal Affective Disorder [SAD]. Furthermore, early-morning bright light induces phase advances of the melatonin cycle in SAD patients (Lewy et al., 1987a). The functional significance of melatonin in SAD remains unclear. With plasma melatonin sampled at 20-min intervals in a series of overnight studies, we found marked phase delays of the cycle, relative to that previously reported for normals, in 4/5 depressed SAD patients. 2,500 lux light exposure at 6-8 a.m. resulted in exponentially declining melatonin levels that approached low daytime baselines within two hours (t1/2 = 45.52 min). All five patients showed clinical remissions as well as phase advances of the melatonin cycle of 0.75 to 3.27 hours (mean, 1.94 +/- 0.84 hours) after one week of daily exposure from 6-8 a.m. and p.m. These results suggest that the combination of early morning and early evening light exposures induces circadian phase adjustments similar to those of morning light alone, by impacting a photosensitive interval when, in SAD, melatonin secretion overshoots its normal nocturnal phase.

Adult↗