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Biomedical subjects

T Cooper

Publications and source records attributed to T Cooper.

At least 55 records · Page 3Linked to original sources
PubMed1994

Effects of parathyroid hormone depletion in dogs with induced renal failure.

Six parathyroidectomized (PTX) and 6 control dogs had renal mass reduced by 15/16, and were studied for effects of parathyroid hormone depletion on progression of renal failure. All PTX dogs and 4 of 6 control dogs survived until necropsy after 32 weeks. Plasma parathyroid hormone concentration was undetectable in PTX dogs throughout the study, but was greater than normal in control dogs. Serum inorganic phosphate (P) concentration was increased in PTX dogs (6.8 +/- 0.1 mg/dl) and in control dogs (7.5 +/- 0.2), but did not differ significantly (P = 0.254) between groups. Ionized blood calcium values (Ca2+) were significantly (P = 0.014) lower in PTX dogs (1.31 +/- 0.01 mmol/L) than in control dogs (1.36 +/- 0.00 mmol/L), but were more variable in PTX dogs. Values in PTX dogs were not significantly different from those in control dogs for glomerular filtration rate (P = 0.914), plasma creatinine concentration (P = 0.903), and urine protein to creatinine ratio (P = 0.756) determined at intervals during the study. Terminal glucose tolerance and plasma insulin concentrations, P tolerance, and renal P excretion did not differ between groups. Histologic comparison of kidneys removed during reduction of renal mass with kidneys removed at necropsy revealed development of lesions in both groups of dogs, and no protective effect from parathyroidectomy. Mineral analysis of aorta, brain, heart, lungs, and skeletal muscle obtained at necropsy revealed no significant difference between PTX and control groups. Renal cortical calcium concentration was significantly (P < 0.05) greater in kidneys obtained at necropsy then in kidneys obtained during nephrectomy, but PTX did not protect renal cortex from calcium deposition.

Animals↗
PubMed1994

Predictors of response to clozapine.

Clinical and biological measures were examined for their relationship to clinical response to clozapine. Associations were found between therapeutic response and the following variables: male gender, paranoid schizophrenia subtype diagnosis, older age at onset of illness, shorter duration of illness, higher levels of pretreatment acute EPS, low pretreatment CSF HVA/5-HIAA, greater decrease in prolactin (PRL) and increase in growth hormone (GH) response to apomorphine stimulation pretreatment and greater inhibition by clozapine treatment of PRL and GH response to apomorphine, and plasma clozapine levels above 350 ng/mL. These results are consistent with other investigators' findings and have practical and heuristic implications for the use of clozapine and understanding its mechanism of action.

Adult↗
PubMed1994

Blood levels of haloperidol and clinical outcome in schizophrenia.

Haloperidol levels in blood were measured in 55 acutely psychotic inpatients with schizophrenia, who were randomly assigned to three fixed doses of oral haloperidol. Nineteen of these subjects received 10 mg/day, 18 received 30 mg/day, and 18 of them received 80 mg/day. All of the subjects were treated under double-blind conditions for 6 weeks or until remission. Haloperidol and reduced haloperidol levels were measured in plasma and red blood cells at the end of 2, 4, and 6 weeks of treatment. There were statistically significant linear correlations between the dose of haloperidol and levels in blood. An examination of data for linear and curvilinear relationships between levels in blood and clinical response did not yield any statistically significant relations. The data did not support the concept of a "therapeutic window." The ratio of reduced haloperidol to haloperidol levels in plasma or red blood cells did not yield any statistically significant correlations to clinical outcome.

Adolescent↗
PubMed1993

Brain morphology, dopamine, and eye-tracking abnormalities in first-episode schizophrenia. Prevalence and clinical correlates.

OBJECTIVE: To characterize the pathophysiology of schizophrenia and to identify biologic markers in first-episode patients with no or little prior treatment exposure. DESIGN: Prospective study of an inception cohort. SETTING: Psychiatric division of an academic medical center with a suburban metropolitan catchment area. PATIENTS: 70 patients in their first episode of schizophrenia (77%) or schizoaffective disorder (23%) with no (70%) or limited prior neuroleptic exposure (30%), and 50 healthy volunteer control subjects. ASSESSMENT MEASURES: Demographic and clinical evaluations of natural history and psychopathology; methylphenidate hydrochloride and apomorphine hydrochloride stimulation tests as measures of central nervous system dopamine activity; brain magnetic resonance imaging; eye-tracking examinations. RESULTS: Preliminary analyses demonstrate that pathobiologic features previously identified in heterogeneous and primarily chronically ill patients are also present in subgroups during their first episode. These include psychotogenic response to methylphenidate (59%), abnormal growth hormone (GH) secretion (50%), abnormal brain morphology (31%), and eye-tracking dysfunction (51%). An association of pathobiologic variables with increased symptom severity and earlier age of onset was observed but not statistically significant. The strongest associations among biologic variables were for the following: GH secretion and psychotogenic response to methylphenidate, which may reflect increased dopamine agonist neural activity; decreased GH response to apomorphine and third-ventricle enlargement, which may represent a neuropathologic correlate of anterior pituitary abnormalities; and morphologic abnormalities of the medial temporal lobe and third ventricle were associated with normal eye tracking, suggesting that these pathobiologic features are mediated by distinct processes. CONCLUSIONS: These phenomena appear to be a consequence of the disease rather than the effects of chronicity, drug treatment, or institutionalization. It remains to be determined if these biologic phenomena will remain stable over time or change with disease progression. A companion article examines the clinical significance of these findings.

Adolescent↗
PubMed1993

The dopamine-serotonin relationship in clozapine response.

The effects of clozapine on the dopamine and serotonin systems may underlie its atypical pharmacologic and clinical profile. To examine this hypothesis, we measured dopamine and serotonin plasma and cerebrospinal (CSF) metabolites and the relationship of these values to treatment response in 19 neuroleptic refractory and intolerant schizophrenic patients. Only a small change in the CSF and plasma homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) levels was found. However, the pretreatment CSF HVA/5HIAA ratio and, to a lesser extent, the CSF HVA level predicted treatment response. These results suggest that the modest relationship between HVA and 5-HIAA and treatment response supports the involvement of both neurotransmitters in the pathophysiology of schizophrenia.

Adolescent↗
PubMed1993

HIV-infected children in the pediatric emergency department.

Forty-three nonhemophiliac, confirmed HIV-positive children followed by the Children's Hospital AIDS Program made 184 visits to the children's Emergency Department (ED) during 1988 and 1989. The mean age was 30 +/- 28 months with a median of 25 months, a mode of 10 months, and a range from two days to 19 years. CD4 counts from within six months of the visit were available in 87% and were low enough to require Pneumocystis carinii pneumonia prophylaxis under current guidelines in 52%. Chief complaints included fever in 50%, respiratory symptoms in 21%, and gastrointestinal symptoms in 8%. The ED discharge diagnosis included fever/possible sepsis in 25%, pneumonia in 17%, otitis media in 9%, and upper respiratory tract infection or viral syndrome in 9%. Overall, an acute infection was identified at 62% of visits; of these, 33% were judged to be serious in nature. A total of 92 blood cultures were drawn, of which eight were positive with the following organisms: Streptococcus pneumoniae (3), Streptococcus faecalis (2), Escherichia coli (1), Torulopsis glabrata (1), and Staphylococcus non-aureus (1, a probable contaminant). Overall, 53% of patient encounters resulted in hospitalization. Patients with a white blood cell count more than 15,000/mm3 were more likely to be hospitalized (87 vs 62%, P < 0.01), though the white blood cell count was not helpful in identifying patients with bacteremia or serious infections. The mean temperature of patients admitted was higher than in those discharged (38.7 vs 37.9 degrees C, P < 0.01). In 1989, an estimated six per 1000 visits to our facility were by HIV-infected children.

AIDS-Related Opportunistic Infections↗
PubMed1993

Cortisol levels, immune status, and mood in homosexual men with and without HIV infection.

OBJECTIVE: Alteration in cortisol levels has been reported in HIV infection and may be related to levels of psychiatric distress and immune function. The goals of this study were to assess cortisol levels in subjects with HIV infection and to determine whether stress-related activation of the hypothalamic-pituitary-adrenal (HPA) axis results in compromised immune function. METHOD: As part of a longitudinal study, the authors assessed urinary free cortisol levels of HIV-positive and HIV-negative homosexual men at four time points during a period of 2 years. Subjects' scores on the Hamilton depression and anxiety rating scales, medical stage of HIV infection, and CD4+ and CD8+ cell counts were also assessed. Repeated measures analysis of variance was used to determine whether subjects' cortisol levels at the four time points differed according to their serological status. Pearson correlation coefficients were computed to examine the relationships among mood ratings, cortisol levels, medical stages, and cell counts. RESULTS: Cortisol levels did not differ significantly between the HIV-positive and the HIV-negative subjects and were not associated with stage of medical illness in HIV infection. An association between cortisol level and depressed and anxious mood was found only at the first assessment. Cortisol level was not associated with CD4+ cell count in either group of subjects. CONCLUSIONS: There were no significant elevations of cortisol levels in the HIV-infected subjects, nor was there consistent evidence for stress-related activation of the HPA axis in either the HIV-positive or the HIV-negative subjects.

Adult↗
PubMed1993

Association of anticholinergic activity of prescribed medications with postoperative delirium.

In a prior study, delirium and plasma anticholinergic drug levels were significantly correlated in 9 of 25 surgical intensive care patients. The present study, using cumulative anticholinergic effects of parent compounds of these patients' medications, found that delirious patients' medication combinations had significantly higher cumulative anticholinergic effects than those of nondelirious patients.

Adult↗
PubMed1993

Effect of cisapride therapy for severe dyspepsia on gastrointestinal symptoms and quality of life.

Quality of life measures have received little attention in evaluation of therapy for dyspepsia. To examine the effect of cisapride on gastrointestinal symptoms and quality of life measures, we studied eight patients with chronic, severe dyspepsia, before and after therapy with cisapride (20 mg three times daily) for 12 months. Gastrointestinal (GI) Total Symptom Score (TSS), Overall Patient Assessment (OPA), and quality of life by both trait (Minnesota Multiphasic Personality Inventory (MMPI)) and physical function (Sickness Impact Profile (SIP)) were measured at base line and at month 12 of cisapride therapy. Results showed significant improvement in TSS, OPA, and the MMPI Depression and Anxiety scales (all, p < 0.05). Improvement in the SIP physical dimension score approached significance (p = 0.065). We conclude that, in this group of patients with severe dyspepsia, both GI symptoms and quality of life measures improved with 12 months of cisapride therapy. These quality of life measures may prove useful in evaluating the efficacy of drug treatment for dyspepsia.

Adult↗
PubMed1993

Influence of hydration state on renal functions of dogs.

Clinically normal dogs were evaluated in states of dehydration, euhydration, and after fluid administration to determine effects of hydration state on renal clearance values. Endogenous creatinine, exogenous creatinine, and [14C]inulin clearances, were determined to measure glomerular filtration rate (GFR); in some experiments p-aminohippurate clearance was determined to measure renal plasma flow. Dehydration caused significant (P < 0.05) decrease in clearance values, compared with euhydration, and clearance values during euhydration were significantly (P < 0.05) less than values obtained after a single gavage with water (30 ml/kg of body weight). Sustained administration of 3 fluid regimens was evaluated for effects on clearance values (treatment A = 30 ml of lactated Ringer's solution/kg/h; treatment B = 30 ml of water/kg by gavage hourly; treatment C = 10 ml of glucose:lactated Ringer's solution/kg/h). All regimens of fluid therapy caused significant P < 0.05), progressive increases in GFR, but treatment C resulted in the most stable GFR values. Increases in clearance values were associated with positive fluid balance; the rate of fluid administration was greater than the rate of urine formation. Data from 285 GFR determinations on 85 dogs were evaluated retrospectively. For each determination, three 20-minute urine collections were made beginning 40 minutes after 30 ml of water/kg was given by gavage. Values between collections were significantly (P < 0.05) different, but varied by < 3%. Comparison of methods for measurement of GFR indicated that endogenous creatinine clearance and [14C]inulin clearance were highly correlated (R2 = 0.82), but mean clearance values were markedly different (mean +/- SEM, 28.70 +/- 0.01 and 37.07 +/- 1.29 ml/min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

High plasma clozapine levels in tardive dyskinesia.

Studies in the literature that attempt to relate neuroleptic plasma levels to the development of tardive dyskinesia (TD) report inconsistent findings. As part of an open, long-term study, 60 schizophrenic and schizoaffective patients were started gradually on a b.i.d. schedule of the atypical antipsychotic drug clozapine. Blood samples were drawn weekly for 6 weeks and analyzed for a variety of constituents including clozapine plasma levels. Patients with higher levels of TD were found to have significantly higher levels of plasma clozapine and a higher ratio of plasma/dose than those with lower levels of TD. Our data suggests that schizophrenics with TD may have different pharmacokinetics, drug metabolism, and elimination processes than those without TD. Higher typical plasma neuroleptic levels may increase susceptibility to TD development. A second hypothesis implies that it is not the higher mean plasma level of a neuroleptic that is associated with TD but the greater fluctuations of plasma levels over time (i.e., a higher variance). This hypothesis is discussed in the context of our data.

Adult↗
PubMed1992

Cloning of a mu-class glutathione S-transferase gene and identification of the glucocorticoid regulatory domains in its 5' flanking sequence.

The expression of a mu-class glutathione S-transferase gene (hGSTYBX) isolated from hamster smooth muscle tumor cells (DDT1 MF-2) is transcriptionally up-regulated by glucocorticoids, and this hormonal regulation is dependent upon protein synthesis. To study the mechanism of regulation, we have cloned and sequenced hGSTYBX genomic DNA including its 5' flanking region. The hGSTYBX gene contains nine exons dispersed over a 6.3-kilobase region. When linked to a chloramphenicol acetyltransferase (CAT) reporter gene, the 5' flanking region was able to direct transcription of the reporter gene. With 5' deletion studies, we have localized the major glucocorticoid-inducible regulatory element between nucleotides -353 and -239. Within this region no classic glucocorticoid response element (TGTTCT) was identified, but four potential helix-loop-helix binding domains are embedded in two 16-base-pair repeats. Another glucocorticoid regulatory domain has been localized between nucleotides -239 and -136. Cycloheximide blocks glucocorticoid-induced transcription of both the -353CAT and -239CAT reporter genes (nucleotides -447 to -12 and nucleotides -239 to -12 of hGSTYBX, respectively, ligated to a CAT reporter gene); therefore, our observations support previous results suggesting that hGSTYBX induction by glucocorticoids is a secondary response.

Amino Acid Sequence↗
PubMed1992

Haloperidol blood levels and clinical effects.

This study explored the relationships between plasma levels and the clinical effects of haloperidol in 176 acutely exacerbated schizophrenic or schizoaffective patients. After a single-blind placebo period of 1 week (period 1), they entered the double-blind period 2 randomly assigned to one of three plasma levels of haloperidol: low (2 to 13 ng/mL), medium (13.1 to 24 ng/mL), or high (24.1 to 35 ng/mL). Patients whose conditions did not improve in period 2 continued on one of the three haloperidol levels (period 3). Periods 2 and 3 lasted 6 weeks each. Only minor differences in clinical responses were noted among the three levels of haloperidol. These results imply that low or moderate doses of neuroleptics are appropriate for many acutely psychotic patients.

Acute Disease↗
PubMed1992

Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium.

Anticholinergic effects of the 25 drugs most commonly prescribed for the elderly were measured by radioreceptor assay. Fourteen had detectable anticholinergic drug levels; 10 of these had levels that have been associated with impairments in memory and attention in normal elderly subjects. These data indicate that patients taking multiple medications may be at increased risk for side effects from psychotropic drugs, most of which have anticholinergic effects.

Age Factors↗
PubMed1992

Enhanced serotonergic responsivity following electroconvulsive therapy in patients with major depression.

Prolactin release in response to fenfluramine hydrochloride (60 mg orally) and placebo was evaluated in 18 medication-free patients with RDC major depressive disorder, endogenous subtype, before and after a series of bilateral treatments with ECT. Before ECT, fenfluramine induced a twofold increase in plasma prolactin levels. This response was significantly enhanced after the ECT series, while baseline prolactin levels and response to the placebo challenge were not altered. There was no significant difference in plasma fenfluramine and norfenfluramine levels during the pre- and post-ECT challenges. These findings suggest that ECT enhances central serotonergic responsivity and extend to depressed patients pre-clinical observations regarding the effect of electroconvulsive shock on serotonergic function.

Depressive Disorder↗
PubMed1992

Impedance plethysmography and thrombo-embolic disease.

This study compares the results of impedance plethysmography with lower limb venography in 68 patients referred for investigation of clinical deep vein thrombosis, and with the results of ventilation/perfusion isotope scans in 125 patients with suspected pulmonary embolism. Impedance plethysmography had a sensitivity of 100% and a specificity of 61% for the detection of thromboses involving popliteal or more proximal veins (30 patients), but a sensitivity of 90% and a specificity of 68% in the detection of thrombosis at any level, because of a low sensitivity in the detection of isolated calf vein thrombosis (60% in 10 patients). It is a non-invasive, portable and low-cost technique and, in centres where anticoagulation is only given to patients with popliteal or more proximal thrombosis, venography may only be necessary if impedance plethysmography is positive. It may also be of value in the assessment of patients with suspected pulmonary embolic disease and an indeterminate ventilation/perfusion lung scan.

Humans↗