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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
PubMed1995

Uncoupling of the noradrenergic-hypothalamic-pituitary-adrenal axis in panic disorder patients.

In this paper the authors examine the interrelationship of both the noradrenergic (NA) system and the hypothalamic-pituitary-adrenal (HPA) axis and its implications for panic disorder (PD). Seventeen PD patients and 16 healthy volunteers were challenged orally 12 weeks apart with the alpha 2-agonist clonidine (13 healthy volunteers and 12 patients repeated the challenge). Between challenges, PD patients were treated with fluoxetine, with 10 of 12 improving at least moderately. Both during the acute phase of the illness and during the phase of pharmacological improvement, patients demonstrated a greater percentage of reductions of plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and plasma cortisol during clonidine challenge. We used correlational matrices to examine the relationship between the NA system, as reflected by plasma MHPG, and the HPA axis, as reflected by plasma cortisol measures. Healthy volunteers exhibited multiple significant "couplings" between either baseline or maximal decrease (delta max) of plasma MHPG, with either baseline or delta max plasma cortisol measures both within the first and second challenges and between the first and second challenges. In contrast, PD patients demonstrated "uncoupling" of the NA system and the HPA axis, with no significant correlations observed between either baseline and/or maximal decrease (delta max) measures of MHPG with the same cortisol measures for either the first or second challenge. The same uncoupling was observed for NA/HPA correlations between the first and second challenges. These data suggest that the hyperresponsivity to clonidine in PD patients persists during fluoxetine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1995

Plasma clozapine levels and clinical response for treatment-refractory schizophrenic patients.

OBJECTIVE: The purpose of this study was to determine if plasma clozapine levels were associated with treatment response. METHOD: To examine this question, neuroleptic nonresponsive patients with schizophrenia or schizoaffective disorder were given clozapine, which was titrated to 500 mg/day by day 14 of treatment, and the dose was held fixed at least through day 21. Subsequently, clozapine doses were adjusted as clinically indicated, up to a maximum of 900 mg/day. Plasma clozapine levels were obtained at weeks 3 and 6, and standard clinical ratings (Brief Psychiatric Rating Scale [BPRS] and Clinical Global Impression) were done at baseline and at weeks 3 and 6. RESULTS: Data from 45 subjects were analyzed. There were no correlations between plasma clozapine levels and change in BPRS scores at treatment weeks 3 and 6. However, when the subjects were classified as responders or nonresponders, therapeutic response was associated with clozapine blood levels above 350 ng/ml. CONCLUSIONS: This study suggest that clozapine blood levels are correlated with clinical response.

Adult↗
PubMed1995

Persistence of blunted human growth hormone response to clonidine in fluoxetine-treated patients with panic disorder.

OBJECTIVE: The authors determined the effects of antipanic treatment with fluoxetine on human growth hormone (GH) response to the alpha 2 agonist clonidine. METHOD: Seventeen patients with panic disorder and 15 healthy volunteers were challenged with clonidine. Thirteen of the patients and 12 of the volunteers were given a second challenge with clonidine 12 weeks later. The patients received open fluoxetine and the healthy subjects received no treatment between challenges. Subjects with high baseline human GH levels (greater than 2 ng/ml) at the first and second challenges were excluded from further analysis. RESULTS: The patients with panic disorder (N = 13 for the first challenge and N = 9 for the second) had significantly lower human GH responses to clonidine than the healthy subjects (N = 14 during the first challenge and N = 9 for the second) during both challenges, despite clinical improvement in eight of the nine patients at the time of the second challenge. CONCLUSIONS: Blunted secretion of human GH in response to clonidine in patients with panic disorder persists despite clinical recovery.

Clonidine↗
PubMed1994

Plasma homovanillic acid levels in first-episode schizophrenia. Psychopathology and treatment response.

OBJECTIVES: To examine plasma homovanillic acid (pHVA) levels in first-episode schizophrenia, to compare pHVA levels in patients and controls, and to assess the association of pHVA levels with psychopathology and treatment response. METHODS: Forty-one patients entered the study, and pHVA levels were measured at baseline and on a weekly basis for up to 6 weeks of open standardized neuroleptic treatment. Psychopathology was evaluated with the Schedule for Affective Disorders and Schizophrenia, the Scale for Assessment of Negative Symptoms, and the Clinical Global Impressions scale. Ten healthy controls were used for comparison of baseline pHVA levels. RESULTS: No differences were observed between patients and controls. Baseline pHVA level was not associated with psychopathology but was associated with time to reach remission. Baseline pHVA levels and week-1 pHVA levels were higher in responders than nonresponders. Regardless of responsiveness, female participants had higher pHVA levels than male participants throughout the study. The pattern of pHVA levels with treatment was similar in all patients with a short-term rise initially and then a decrease toward baseline values. CONCLUSIONS: These findings suggest that pHVA levels have prognostic significance for response and time to reach remission. Qualitative and quantitative differences between first-episode patients' pHVA levels and studies using a long-term, neuroleptic-exposed population suggest that changes occur with neuroleptic treatment or the progression of the illness.

Adult↗
PubMed1994

Methylphenidate response, psychopathology and tardive dyskinesia as predictors of relapse in schizophrenia.

Despite the proven efficacy of acute and maintenance pharmacotherapy in schizophrenia, practical methods for identifying patients who require continuous treatment to prevent relapse have not been established. We hypothesized that a pathologic overactivity of mesolimbic and mesocortical dopamine neural systems, that mediates positive psychotic symptoms in the acute phase of the illness, persists in some outpatients who are vulnerable to relapse despite appearing clinically stable. To test and determine if putative measures of central nervous system dopamine activity predict outcome, 41 stable outpatients receiving neuroleptic maintenance treatment underwent provocative tests with methylphenidate in a randomized double-blind placebo controlled design in which behavioral, neuromotor, biochemical, and cardiovascular responses were measured. Patients were then withdrawn from medication and monitored for 52 weeks, or until relapse. The results indicate that psychotic symptoms and their activation by methylphenidate, and the presence of tardive dyskinesia are associated with each other and with a higher risk of relapse. These findings partially support our hypothesis and offer potentially useful measures for the identification of candidates for reduced dose neuroleptic maintenance treatment strategies in schizophrenia.

Adolescent↗
PubMed1994

Relation of plasma fluphenazine levels to treatment response and extrapyramidal side effects in first-episode schizophrenic patients.

OBJECTIVE: The aim of this study was to determine the relation between plasma fluphenazine levels and clinical response in first-episode schizophrenic patients. METHOD: Data from 36 first-episode schizophrenic or schizoaffective inpatients diagnosed according to the Research Diagnostic Criteria were evaluated. The patients received open, standardized treatment with fluphenazine, 20 mg/day, for at least 4 weeks. Psychopathology was assessed biweekly, and plasma fluphenazine levels were ascertained weekly. Patients were classified as responders or nonresponders, and correlations between their neuroleptic levels and ratings of psychopathologic and extrapyramidal symptoms were computed. RESULTS: Plasma fluphenazine levels for weeks 1 through 4 were significantly correlated with each other but were not correlated with age, gender, diagnosis, or race. Mean neuroleptic levels (weeks 3 and 4) were not different between responders and nonresponders and were not correlated with measures of psychopathology or extrapyramidal symptoms. CONCLUSIONS: These results do not indicate an association between plasma fluphenazine levels and response to treatment or extrapyramidal side effects in first-episode schizophrenia. The disparity between the results of this study and those of previous studies may be due to methodological differences or to a biologically based difference between first-episode and chronic patients.

Adolescent↗
PubMed1994

Post-anaesthetic pulmonary oedema following upper airway obstruction.

Twelve cases of post-anaesthetic pulmonary oedema (PO) secondary to upper airway obstruction (UAO) are reported. All were adult male patients undergoing uneventful elective surgical procedure under general anaesthesia. Post-anaesthetic laryngospasm was the single most important factor for the upper airway obstruction (UAO) in 5 (41.6%) patients. PO secondary to partial UAO in drowsy patients was observed in 4 (33.3%) patients. UAO due to foreign body was responsible for PO in two patients. A combination of negative intrathoracic pressure, hypoxia and associated hyperadrenergic state were the most likely causes of PO in these patients with UAO. Early recognition, maintenance of patent airway and adequate oxygenation via face mask or endotracheal tube with mechanical ventilation resolved the syndrome within 6-36 hours in all of these patients. Invasive haemodynamic monitoring or aggressive drug therapy were not applied in any of the patients. A heightened awareness among anaesthesiologists of the varied causes of post-anaesthetic UAO leading to PO may help reduce the occurrence and facilitate early management of the potential complications.

Adolescent↗
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↗