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Biomedical subjects

T Cooper

Publications and source records attributed to T Cooper.

At least 91 records · Page 5Linked to original sources

Immuno-competent cells in the murine epididymis.

Cryostat sections of epididymides from mice were stained with monoclonal antibodies against immuno-competent cells. This investigation was undertaken to gain basic data about the distribution of macrophages. T lymphocytes, MHC class II and MIF in the normal murine epididymis to establish the mouse as a model for immunological epididymal research. The most important findings were as follows. (1) Macrophages, T lymphocytes, MHC class II and MIF positive cells were distributed similarly in the caput, corpus and cauda epididymis. (2) Macrophages were the most frequent leucocytes and the majority were located in the peritubular layer. (3) The MHC class II determinant was also expressed mostly in the peritubular layer and interstitium. These cells were similar in appearance and location to macrophages. (4) Significantly fewer T lymphocytes were found and their main location was the interstitium. T-helper and T-suppressor/cytotoxic lymphocytes did not differ significantly in their regional or histological distribution patterns. (5) The ratio of T-helper to T-suppressor/cytotoxic lymphocytes was 1:1. (6) MIF was detected almost exclusively in blood vessels and the surrounding connective tissue. (7) No invasion of leucocytes into the epididymal lumen was observed. It is concluded that macrophages seem to be the most important immunological cell type in the murine epididymis.

Animals↗

Neuroleptic augmentation with alprazolam: clinical effects and pharmacokinetic correlates.

Alprazolam added to stable doses of neuroleptics in nine schizophrenic patients was associated with a 20%-30% mean reduction in positive and negative symptoms, although clinical response was variable and in some patients particularly brisk. The authors examined the possibilities of a pharmacokinetic effect of alprazolam on neuroleptic plasma levels and of a clinical effect of alprazolam. The modest increase in mean neuroleptic plasma levels did not correlate with clinical change, but those patients with the highest alprazolam plasma levels tended to show more robust clinical responses.

Adult↗

Who manages the managers? The 1989 Harvey Cushing oration.

New medical knowledge is emerging at a tremendous rate. Diseases such as Alzheimer's disease. Parkinson's disease, cancer, and others (diseases once considered beyond the scope of medicine) are receiving a great deal of attention. Yet it is a paradox that, at a time when we are learning more about the biology of the human being, it is more difficult to creatively develop the new knowledge into diagnostic tests, surgical interventions, and preventive strategies. The pace of biomedical innovation is being slowed by an increase in the intervention of nonmedical "managers of care." The driving force behind managed care is concern over cost. The managers of medical care have sought to control costs by controlling the doctor's decision making. This is the focus of managed care. The physicians of today, therefore, face a remarkable challenge. They must respond to the needs of patients while being held accountable to an increasing number of overseers in the public and private sectors. These managers of care justify their activities on the notion that the patient will be better off and the cost less if the doctor-patient encounter is regulated by protocols, statistical comparison, utilization review, and fee schedules. While doctor's decisions are being managed by others, who is managing the managers? The answer should be the medical community, principally doctors. Unfortunately, the answer at the moment is the payors--governmental reimbursement agencies, intermediaries, employers, hospitals, or new corporations designed to manage medical costs. The challenge to the physician is to retain the responsibility for those things for which he or she is held accountable. The challenge should not be ignored.

Costs and Cost Analysis↗

Effect of polymyxin B on hemoglobin-mediated hepatotoxicity.

In previous studies, enhanced toxicity of hemoglobin when combined with endotoxin has suggested a specific binding site. This binding may take place even when endotoxin-free hemoglobin is administered, due to some low levels of endotoxin usually present in the portal vein. To test this hypothesis, we administered endotoxin-free, stroma-free human hemoglobin (SFH) to rabbits in doses shown previously to be hepatotoxic or lethal. A second group of rabbits received the anti-endotoxin antibiotic polymyxin B (PB) to inactivate endotoxin, followed by a dose of SFH. A control group received intravenous PB alone. There was no differences in the incidence of hepatotoxicity among these three groups. To show the binding interactions of endotoxin with PB and endotoxin with hemoglobin, an experiment using toluidine blue was performed. According to this study, specific binding of hemoglobin with endotoxin did not occur. Our results do not agree with previous suggestions that hemoglobin-mediated hepatotoxicity is due to the interaction in vivo of hemoglobin with low levels of endogenous endotoxin.

Absorption↗

Cyclic AMP and cyclic GMP in hyperresponsiveness.

Cyclic-AMP has been shown to cause a hyperresponse in blood pressure change in conjunction with norepinephrine in the anesthetized rat system. Recent experiments show that the antagonist to angiotensin II, Sar1-Thr8 angiotensin II, abolishes the hyperresponse produced by c-AMP. This is interpreted to mean that the added response caused by c-AMP is mediated through angiotensin II. When the antagonist is removed, the hyperresponse is observed to return. The experiments with cyclic-GMP indicate that the hyperresponse seen with c-AMP is not only absent, but a constant decrease in response to norepinephrine is observed as long as c-GMP is present. The decrease in blood pressure change in the presence of c-GMP suggests that the 10-5M c-GMP causes a relaxation of vascular smooth muscle. These two cyclic nucleotides seem to produce their effects by two completely different mechanisms.

Angiotensin II↗

Dexamethasone suppression test and plasma dexamethasone levels in bulimia.

A 1-mg dexamethasone suppression test (DST) was carried out in 66 women with bulimia and in 26 age- and sex-matched controls. Blood samples were obtained at 4 PM on the day following dexamethasone ingestion, and levels of cortisol and of dexamethasone in the plasma were measured. Thirty-two percent of the patients vs only 7% of the controls had plasma cortisol levels of 140 nmol/L (5 micrograms/dL) or greater following the DST (a positive DST). The plasma levels of dexamethasone varied substantially, and there was a significant inverse relationship between the plasma level of cortisol and that of dexamethasone. Patients with positive DST results had lower levels of plasma dexamethasone than did those with negative DST results, and the mean plasma level of dexamethasone was lower in the bulimic group than in the control group. These results suggest that factors other than a disturbance of hypothalamic-pituitary-adrenal activity may contribute to positive DST results in bulimia.

Adult↗

Early pharmacokinetics and clinical effects of oral D-amphetamine in normal subjects.

Seven normal subjects received 0.25 mg/kg D-amphetamine orally, both after an overnight fast and again after a standard breakfast. Plasma levels, subjective and cardiovascular effects, and observer-rated activation were assessed hourly for 5 hr. Food did not affect amphetamine levels. Plasma levels peaked at 2-3 hr. Maximum cardiovascular effects generally occurred at 1 hr, whereas maximum behavioral and subjective effects occurred at 2 hr. Subjective and behavioral effects declined thereafter, in spite of substantial amphetamine levels. A separate group of 8 subjects received 0.5 mg/kg D-amphetamine orally. Plasma levels, subjective and cardiovascular effects, and activation ratings were assessed hourly for 4 hr. Maximum plasma levels were approximately twice those seen in the first group. In this case, plasma levels peaked at 3-4 hr; blood pressure and subjective and behavioral effects were all maximal at 2-3 hr and were declining by 4 hr, in spite of stable or rising plasma levels.

Administration, Oral↗

Clinical predictors of response to antidepressants in elderly patients.

A group of 42 patients, ages 55 and above, suffering from major depression were examined in an attempt to isolate clinical variables that would predict response to antidepressants. These patients were part of a placebo-controlled, double-blind study and were given either nortriptyline or phenelzine for 5-7 weeks. There was no significant difference in response rates between patients subclassified as endogenous or nonendogenous by either RDC or Newcastle criteria. No difference in response rates was found between the DSM-III melancholic and nonmelancholic subtypes. Neither drug preferentially treated a subtype. None of the 21 variables representing symptoms, demographic traits, or characteristics of the depressive illness were found to be significant predictors of antidepressant response.

Aged↗

Prediction of response to nortriptyline and phenelzine by platelet MAO activity.

Thirty-seven depressed patients over the age of 55 were treated for 5-7 weeks with either nortriptyline, a tricyclic antidepressant, or phenelzine, a monoamine oxidase (MAO) inhibitor. Patients' platelet MAO activity was measured following a drug washout period before treatment. Patients with higher MAO activity had a better response to treatment, regardless of which drug was used.

Aged↗

Cyclic AMP, the hyperresponsiveness factor from hog kidney.

The isolation and identification of a material present in the plasma of hypertensive dogs and hypertensive human patients has been under study since 1972. The earliest experiments in relation to this work, noted that plasma from hypertensive dogs cause a hyperresponse to norepinephrine when both were administered by way of the vein. Employing a rat assay system that consisted of an anesthetized rat with polyethylene catheters in the vein for giving norepinephrine and the test fractions and a catheter in the artery for blood pressure monitoring, fractions from hog kidney were tested for hyperresponsiveness activity. The active material is very comparable to cyclic AMP in molecular weight, ultraviolet spectrum, paper chromatography, Enzyme hydrolysis and activity in the anesthetized rat system. This evidence indicates that the hyperresponsiveness factor of renal origin is cyclic AMP.

Angiotensin II↗

The effect of imipramine treatment on brain serotonin receptors and beta-adrenoceptors and on pineal beta-adrenergic function in adult and aged rats.

The effect of age and of imipramine treatment on cortical serotonin and beta-adrenergic binding sites and on pineal N-acetylserotonin and melatonin were examined in Fischer-344 rats. Cortical serotonin-1 and -2 receptor binding was reduced by 15 and 22.5% respectively, in 24 vs. 6 months old animals. Ten single daily imipramine (10 mg/kg) injections in the aged animals resulted in reductions in both types of serotonin sites, while in adult animals significant binding reduction occurred only at the 5HT2 site. Cortical beta-adrenoceptor binding was also diminished in the aged rats. Imipramine treatment elicited a significantly greater decrease in these adrenergic sites in the aged (39.2%) than in the adult (27.6%) animals. In the pineal gland, N-acetylserotonin and melatonin content were reduced by age; imipramine treatment induced decreases in both indoles in the adult animals and a reduction in N-acetylserotonin in the aged animals. These age-related effects of imipramine on cortical serotonin receptor and beta-adrenoceptor binding and on pineal indoles may be a consequence of the higher drug and metabolite (desmethylimipramine) blood and tissue concentrations which were found in the aged animals.

Aging↗

Imipramine in adolescent major depression: plasma level and clinical response.

Thirty-four adolescents with mean age 14.25 years who met RDC criteria for major depressive disorder as assessed with the K-SADS, were treated for 6 weeks on a fixed schedule of imipramine hydrochloride titrated to a dosage of 5.0 mg/kg/day except as limited by side effects. Mean dose was 246 mg/day (4.5 mg/kg/day). In spite of good indications of compliance with treatment only 44% of the adolescents improved to the level of no or only slight depressed mood or anhedonia, though most had less depressive symptomatology at the end of treatment. There was neither a linear nor curvilinear relationship between total plasma level of IMI plus DMI and clinical response, despite a wide range of both plasma level (77 ng/ml to 986 ng/ml) and outcome. Adolescents with associated separation anxiety had significantly poorer response to treatment of their depressive disorder than those with major depression alone. Poor response was also weakly associated with being female, having endogenous subtype of depression, and having higher plasma IMI (but not DMI) level. In the context of similar studies of IMI on depression in other age groups, it is hypothesized that high levels of sex hormones during adolescence and young adulthood may interfere with IMI's antidepressant effects. It is concluded that other types of antidepressants should be tested in adolescents with major depression.

Adolescent↗

Different pattern of association of beta-endorphin and cortisol responses to dextroamphetamine in postmenopausal women and young men.

A negative correlation between plasma beta-endorphin and cortisol responses to 0.15 mg/kg dextroamphetamine i.v. was found in a group of seven normal postmenopausal women, while the responses of the two hormones were positively correlated in nine normal young men. These results suggest that even though the adrenocorticotropic hormone (ACTH)-cortisol and beta-endorphin are usually regulated by the same mechanism (both ACTH and beta-endorphin are derived from proopiocortin), there are situations in which these systems can be associated in a different pattern. The elucidation of these situations may contribute to the understanding of regulatory mechanisms of the two systems.

Adult↗