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Biomedical subjects

T B Cooper

Publications and source records attributed to T B Cooper.

At least 181 records · Page 10Linked to original sources
PubMed1987

A placebo-controlled comparison of the effect of nortriptyline and phenelzine on orthostatic hypotension in elderly depressed patients.

Seventy-five patients, 55 years or older, were treated for major depression with either nortriptyline, phenelzine, or placebo during a 7-week period. There was a significantly greater mean orthostatic fall in systolic pressure in patients treated with nortriptyline and phenelzine as compared to the placebo group, but no significant difference was evident between the nortriptyline and phenelzine groups. The orthostatic changes appeared during the first week of treatment and were not correlated with plasma level of nortriptyline, percent platelet monoamine oxidase inhibition, or pretreatment orthostatic changes.

Aged↗
PubMed1987

A reappraisal of surgical intervention for acute myocardial infarction.

Eighty-three patients underwent coronary artery bypass during acute evolving myocardial infarction 6.8 +/- 2.8 hours after the onset of symptoms. Linear discriminant analysis of preoperative variables identified predictors of mortality with an accuracy of 84%. Significant predictors in decreasing order of importance were cardiogenic shock, age over 65 years, left ventricular ejection fraction less than or equal to 0.30, cardiac index less than or equal to 2.0 L/min/m2, and absent collateral flow. Time to reperfusion did not influence outcome nor did the infarct-related artery. Hospital mortality was 15.6% (13/83). Among 51 low-risk patients under 65 years of age without cardiogenic shock, there were three deaths (5.9%). Follow-up angiography was performed in 21 patients. The graft patency rate was 94%. Left ventricular ejection fraction improved from 0.39 +/- 0.10 to 0.49 +/- 0.11 (p less than 0.05). Left ventricular end-systolic volume decreased from 53.2 +/- 19.3 ml/m2 to 41.4 +/- 16.8 ml/m2 (p less than 0.05), and end-diastolic volume remained unchanged: 86.2 +/- 21.2 ml/m2 before operation and 78.7 +/- 24.0 ml/m2 after operation (no significant difference). Regional ejection fraction of the infarct area, determined by the centerline method, increased 0.23 +/- 0.15. In contrast, among 215 patients treated by nonsurgical reperfusion (intracoronary thrombolysis or angioplasty, or both), mortality was 13.5%. In this group, reperfusion was successful in 144 patients (67%) and 89 underwent follow-up angiography. Persistent patency of the infarct artery was demonstrated in 73 (82%). Ejection fraction increased from 0.45 +/- 0.10 to 0.50 +/- 0.15 (p less than 0.05). We conclude that preoperative variables enable identification of patients with evolving acute myocardial infarction in whom coronary artery bypass is associated with low operative mortality and improved ventricular performance.

Coronary Artery Bypass↗
PubMed1987

Review of haloperidol blood level and clinical response: looking through the window.

The studies of relationship between haloperidol plasma levels and clinical response in schizophrenia have yielded variable results. A therapeutic window for haloperidol may exist, but the evidence for it is inconsistent. Future studies of this problem using larger patient samples would permit the investigation of interactions between the clinical predictors and the haloperidol plasma levels in the determination of clinical outcome. Although the reduced haloperidol in plasma as well as the red blood cell levels of haloperidol and reduced haloperidol or ratios of the metabolite to parent compound may also be related to clinical outcome, the evidence for this relationship is very tentative. More research is needed before routine clinical monitoring of haloperidol blood levels can be recommended.

Dose-Response Relationship, Drug↗
PubMed1987

Prospective study of scheduled withdrawal from nortriptyline in children and adolescents.

Thirty 6- to 16-year-old subjects were gradually tapered from their maintenance dose of nortriptyline while being monitored for withdrawal effects. Five subjects had brief gastrointestinal distress that did not require the administration of an extra dose. The results of this open study suggest that scheduled tapering of nortriptyline will preclude withdrawal symptoms in most pediatric patients.

Adolescent↗
PubMed1987

Prediction of individual dosage of nortriptyline in depressed elderly outpatients.

Individual daily dosages of nortriptyline (NT) can be predicted from administration of a 50-mg or 100-mg single test dose, with a determination of the plasma level 24 hours later. Because the 50-mg or 100-mg test dose used in previous studies may cause unmanageable acute side effects in elderly patients, a 25-mg NT test dose was used to establish a 24-hour plasma level in 18 physically healthy, moderately depressed, geriatric outpatients. Correlations between the 24-hour test dose plasma level and steady state levels were done for maintenance dosages of 50, 75, and 100 mg/day. A nomogram was made from the regression equations to predict the dosage required to achieve a steady state concentration within a 50 to 150 ng/ml range. The importance of the ability to predict NT dosage requirements in geriatric patients is indicated by findings that at daily NT doses of 50 and 100 mg, nearly one-half of subjects had steady state levels below or above 50 or 150 ng/ml, respectively.

Aged↗
PubMed1987

Child and adolescent nortriptyline single dose pharmacokinetic parameters: final report.

This is the final report of a study of single dose pharmacokinetic parameters of nortriptyline in children and adolescents 5 to 16 years old (N = 64). The data were analyzed separately for the 5- to 12-year-olds (N = 41) and for the 13- to 16-year-olds (N = 32). The results confirm the preliminary findings of the similarity of the pharmacology of nortriptyline between the pediatric and adult age groups with respect to a logarithmically linear rate of elimination and a wide interindividual rate of metabolism. The 5- to 12-year-olds had a significantly shorter mean half-life and a significantly greater mean apparent oral clearance than the 13- to 16-year-olds. The mean half-life in the 5- to 12-year-olds was 20.8 +/- 7.2 (range, 11.2 to 42.5) hours and in the 13- to 16-year-olds was 31.1 +/- 19.8 (range, 14.2 to 89.4) hours. A twice a day dosage regimen is recommended for the entire 5- to 16-year-old group based on their range of half-lives.

Adolescent↗
PubMed1986

Brain regional [3H]flunitrazepam binding in rats chronically treated with bupropion or B.W.306U.

After 21 days of twice daily i.p. injections of bupropion (10 mg/kg), B.W.306U (10 mg/kg) or saline, 5 rat brain regions were removed for [3H]flunitrazepam binding assay. Scatchard analysis of the binding data revealed no change in the Bmax in any brain regions in drug-treated rats compared to controls. There was, however, a significant change in the Kd value in the limbic forebrain of B.W.306U-treated rats.

Animals↗
PubMed1986

Comparative efficacy and safety of MAOIs versus TCAs in treating depression in the elderly.

This comprehensive study investigated both the role of antidepressant drugs in the treatment of affective disorders of later life and their safety with careful clinical and pharmacological monitoring. A 7-week double-blind comparison was made of the efficacy and safety of nortriptyline (a tricyclic), phenelzine (a monoamine oxidase inhibitor), and placebo. The results indicated a response rate of approximately 60% for both nortriptyline and phenelzine versus a 13% response rate for placebo. Anticholinergic side effects were more frequently reported in the nortriptyline group. Orthostatic symptoms were reported with similar frequency in both drug groups. Overall, both drugs were well tolerated.

Aged↗
PubMed1986

Modification of ligand binding to membranes by a soluble acceptor. Alpha-1-acid glycoprotein attenuates 3H-imipramine binding to cerebral membranes.

The effect of individual plasma proteins on the binding of 3H-imipramine (3H-IMI) was investigated, using rat cerebral membranes as the binding site source. Addition of alpha-1-acid glycoprotein (aAGLP) to an incubation medium containing 4 nm 3H-IMI resulted in a concentration-dependent inhibition of 3H-IMI binding, with an IC50 value of 0.53 microM. Albumin (0.7 mM) and gamma globulin (3 microM) had no apparent effect. Scatchard analyses of 3H-IMI binding in the presence and absence of 0.5 microM aAGLP revealed that the inhibition of 3H-IMI binding was associated with an increased Kd, with no appreciable change in Bmax. The inhibitory action of platelet-free plasma (PFP) on 3H-IMI binding to cerebral membranes was eliminated after treatment of PFP with specific antibodies to aAGLP. It is suggested that the inhibition of 3H-IMI binding to cerebral membranes by PFP is due, at least partially, to the presence of aAGLP in the plasma. The observed inhibitory effect is consistent with a competition for the ligand between the membrane binding site and the soluble protein acceptor. These findings may explain the serum effect confounding radioreceptor assays of various drugs.

Animals↗
PubMed1986

Effect of plasma from patients containing bupropion and its metabolites on the uptake of norepinephrine.

The uptake of norepinephrine into cortical punches from the brain of the rat was studied in the presence of buffer and plasma from patients containing bupropion and its metabolites. Even though bupropion and its metabolite (compound II) were equipotent in inhibiting the uptake of NE in buffer, compound II was twice as active as bupropion in the presence of human plasma. When the inhibition of uptake of NE in the presence of plasma, obtained from patients on bupropion on steady-state, was correlated with levels of bupropion and its metabolites (II, III, IV) a highly significant correlation was seen in the presence of compound II. Since this compound accumulated in plasma from patients 20-100 times that of the parent compound, the mode of action of bupropion may in part be due to the effect of this compound on the uptake of NE.

Animals↗
PubMed1986

Down regulation of beta-receptors by bupropion and its major metabolite in mouse brain.

Mice were treated with bupropion Compound II (major metabolite of bupropion) or desmethylimpramine (DMI) twice a day intraperitoneally for either 1 or 3 weeks. The binding of dihydroalprenolol and spiroperidol in the frontal cortex and limbic forebrain areas were analyzed. There was a significant reduction in beta-receptors in the frontal cortex induced by DMI at both times examined. Bupropion showed a significant reduction of beta-receptor in the frontal cortex by 3 weeks. Though propiophenone did not have any significant effect on beta-receptors in the frontal cortex, it down-regulated beta-receptors in the limbic forebrain area significantly by 1 and 3 weeks. There was no significant effect of buropion or propiophenone on the binding of spiroperidol either in the cortex (S2 receptor) or in the limbic forebrain (dopaminergic). These results show that bupropion may exert part of its clinical effect through its metabolite propiophenone.

Animals↗
PubMed1986

Inhibition of 3H-imipramine binding by plasma from depressed and normal subjects.

The inhibition by human plasma of 3H-imipramine (3H-IMI) specific binding to rat cerebral membranes was investigated using platelet-free plasma (PFP) from normal and depressed subjects. The specific binding of 3H-IMI at a ligand concentration of 4 nM decreased with increasing PFP volumes, reaching 50% inhibition following the addition of 10-13 microliters PFP to a final incubation volume of 250 microliters. The extent of this inhibition was the same using PFP from controls or depressed patients. The inhibitory activity was associated with plasma proteins. Scatchard analysis of 3H-IMI binding in the presence and absence of PFP indicated that the inhibitory effect was associated with an increased Kd without an appreciable change in Bmax. It is suggested that an endogenous acceptor in the PFP, such as alpha 1-acid-glycoprotein may be responsible for the observed inhibition of 3H-IMI binding to the cerebral membranes.

Adolescent↗
PubMed1986

Relationship of platelet MAO activity to characteristics of major depressive illness.

Sixty-seven patients (greater than or equal to 55 years of age) with major depressive disorder had pretreatment assays of platelet monoamine oxidase (MAO) activity. As in previous studies, women had higher MAO activity than men, and MAO activity was positively correlated with age. Patients with melancholia (DSM-III) had significantly higher MAO activity than those without melancholia. This finding may reflect the higher MAO activity associated with the symptoms of anhedonia and mood autonomy. Anxiety also was correlated with higher MAO activity, as was a positive family history of depression. In addition, postdexamethasone cortisol levels were correlated with platelet MAO activity.

Age Factors↗
PubMed1986

The nephrotoxicity of Isotropis forrestii in sheep.

Sheep were drenched with a single toxic dose of dried and milled Isotropis forrestii in water. Intoxication resulted in early onset of glycosuria, enzymuria and proteinuria. Terminal gross lesions included pale kidneys and perirenal oedema. Histologically and ultrastructurally the renal lesions were typical of primary nephrotoxicosis, with extensive proximal tubular epithelial necrosis. The tubular damage was sufficient to cause acute primary renal failure, characterised by oliguria, azotemia and failure of urinary concentrating mechanisms.

Animals↗
PubMed1986

Preliminary data on the relationship between nortriptyline plasma level and response in depressed children.

Twenty-two subjects 6-12 years old who met Research Diagnostic Criteria and DSM-III criteria for major depressive disorder received a fixed daily dose of nortriptyline during an 8-week protocol. Weekly plasma levels were measured; the raters performing behavioral assessments were blind to these levels. There was a highly significant difference between the mean steady-state plasma levels and the milligram-per-kilogram doses of the responders and nonresponders. The data suggest that the lower limit of the therapeutic range of nortriptyline in children (over 60 ng/ml) is similar to that reported for adults. The disadvantages of the use of a milligram-per-kilogram dose rather than a pharmacokinetic approach are discussed.

Age Factors↗
PubMed1986

Pharmacokinetics of desipramine in Caucasian and Asian volunteers.

The plasma levels of 20 healthy Asian subjects who received a single dose of desipramine were compared with those of 20 healthy Caucasian subjects who received such a dose. The groups differed significantly only in that Asian subjects had an earlier time of peak serum concentration.

Adult↗
PubMed1985

Serotonin depletion induced by reserpine is attenuated by prophylactic administration of lithium.

Prophylactic administration of lithium significantly attenuated the serotonin depleting effects of reserpine. In rat brain, lithium did not change the capacity of the storage protein, serotonin binding protein to bind the amine either in vivo or in vitro nor did it change its sensitivity to reserpine. However, the chronic administration of lithium significantly decreased reserpine levels in plasma and brain tissue of treated rats compared with rats which were treated only with reserpine. It is concluded that the antagonism between reserpine and lithium does not involve the serotonin binding protein but may be due to the lithium-induced reduction of reserpine levels.

Animals↗