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Biomedical subjects

M Arato

Publications and source records attributed to M Arato.

At least 19 recordsLinked to original sources

A 1-year, double-blind, placebo-controlled trial of ziprasidone 40, 80 and 160 mg/day in chronic schizophrenia: the Ziprasidone Extended Use in Schizophrenia (ZEUS) study.

We evaluated relapse in patients with stable, chronic schizophrenia over a 1-year period; inpatients were randomized to ziprasidone 40 mg/day (n = 72), 80 mg/day (n = 68), 160 mg/day (n = 67) or placebo (n = 71). The probability of relapse (Kaplan-Meier) at 1 year was significantly lower in the ziprasidone 40, 80, and 160 mg/day groups (43%, 35% and 36%, respectively) compared to placebo (77%; P = 0.002, P < 0.001 and P < 0.001, respectively). In those patients who remained on treatment for at least 6 months, only 9% subsequently relapsed on ziprasidone compared to 42% on placebo (P = 0.001). All three doses of ziprasidone were significantly superior to placebo on Positive and Negative Syndrome Scale (PANSS) efficacy variables (all P < 0.05). Ziprasidone was associated with a significantly greater mean improvement in the PANSS negative symptom subscale compared to placebo (P < 0.05). Discontinuation due to adverse events was similar with ziprasidone and placebo. Ziprasidone treatment was indistinguishable from placebo in assessments of movement disorders and was not associated with weight gain or cardiovascular abnormalities. These results demonstrate that ziprasidone was effective in reducing the frequency of relapse and was associated with long-term improvement in negative symptoms. Ziprasidone was well tolerated in this population of patients with chronic, stable schizophrenia.

Adolescent↗

Gender-dependent dissociation between oxytocin but not ACTH, cortisol or TSH responses to m-chlorophenylpiperazine in healthy subjects.

m-Chlorophenylpiperazine (m-CPP), a serotonin (5-HT) agonist with some selectivity for the 5-HT2C receptor subtype, which is widely used to examine 5-HT receptor function in human subjects, has been found to induce oxytocin and thyrotropin (TSH) responses in rodents. This study examined whether m-CPP had any effect on plasma oxytocin, TSH and aldosterone concentration in healthy volunteers using a double-blind, placebo-controlled crossover design. Plasma adrenocorticorticotropic hormone (ACTH) and cortisol responses, two generally accepted markers of m-CPP-induced 5-HT receptor activation, were measured in parallel. Male subjects (n=7) received placebo, 0.25 and 0.5 mg/kg oral m-CPP. In female subjects (n=5), the effects of placebo and 0.25 mg/kg m-CPP were studied. After placebo, given in the morning, ACTH, cortisol, TSH and aldosterone concentrations decreased over time. m-CPP 0.25 mg/kg avoided decreases in ACTH, cortisol and TSH concentrations; these responses were significant. At the dose of 0.5 mg/kg, m-CPP caused increase in ACTH, cortisol, TSH and aldosterone concentrations. Significant plasma oxytocin responses were found in female subjects only; thus this effect of m-CPP was statistically significantly gender dependent. Other responses to m-CPP were similar in male and female subjects. The present results suggest that there are clear differences, including dose and gender-dependent dissociations, among the 5-HT receptor agonist m-CPP-induced neuroendocrine responses.

Adrenocorticotropic Hormone↗

Ten-year outcome of tardive dyskinesia.

OBJECTIVE: The purpose of this study was to assess the long-term outcome of patients with tardive dyskinesia. METHOD: A group of 122 neuroleptic-treated Hungarian outpatients were assessed for tardive dyskinesia on the Abnormal Involuntary Movement Scale and the Tardive Dyskinesia Rating Scale by the same rater over a 10-year period. RESULTS: Sixty-three of the patients received both 5- and 10-year follow-up assessments and are the subjects of this report. The overall prevalence of tardive dyskinesia in this group changed little over time; it was 30.2% at baseline, 36.5% at 5 years, and 31.7% at 10 years. However, there were changes in the tardive dyskinesia status of individual patients; 11 patients had remissions, and 12 who did not have tardive dyskinesia at the baseline assessment had developed it by the 10-year assessment. These two subgroups did not differ significantly on demographic and drug history variables. Outcome of tardive dyskinesia was not significantly related to neuroleptic treatment or to age. CONCLUSIONS: The data of this 10-year follow-up study provide evidence for the long-term stability of tardive dyskinesia and for the feasibility of maintenance neuroleptic therapy for chronic psychotic patients who have tardive dyskinesia.

Adult↗

Serotonergic interhemispheric asymmetry: neurochemical and pharmaco-EEG evidence.

1. Postmortem neurochemical investigations revealed interhemispheric asymmetry in the mediofrontal region of human brain. Significantly higher right hemisphere serotonin metabolite (5HIAA) content as well as increased maximal imipramine binding (IB) were found in the right hemisphere than in the left side. 2. IB did not show a gender difference in the mediofrontal area. However, women had higher IB in the right orbital frontal cortex than did men. 3. In vivo pharmaco-EEG results tend to support the postmortem neurochemical data. Intravenous chlorimipramine resulted in an asymmetric topographic distribution of the P300 auditory evoked potential, peak amplitudes were shifted to the right hemisphere.

Adult↗

Biochemical assay of Alzheimer's disease--associated protein(s) in human brain tissue. A clinical study.

The concentration of Alzheimer's disease-associated protein (ADAP) was measured in postmortem brain tissue samples of temporal or frontal cortex from 111 human brains using a sandwich immunoassay. Alzheimer's disease-associated protein has three major ALZ-50-reactive subunits, including A-68. This assay utilizes ALZ-50 and a rabbit antibody raised against a highly ADAP-enriched brain protein fraction. The frequently observed cross-reactivity of ALZ-50 with normal brain components in direct immunoassays is minimized by this configuration. There were 27 normal controls, 28 neurologic disease controls, and 56 Alzheimer's disease cases. The normal control and neurologic disease control cases had essentially no detectable level of ADAP, while ADAP was clearly detected in 85.7% of the Alzheimer's disease cases. Clinical dementia, neuritic plaques, and old age per se are not correlated with increased ADAP levels. This biochemical assay of ADAP may prove to be helpful as an adjunct in the clinicopathologic diagnosis of Alzheimer's disease.

Aged↗

A quantitative analysis of placental vasculature in the third-trimester fetus with autosomal trisomy.

Growth disturbance in the trisomic fetus is believed to be primarily fetal in origin. There has been only sparse description of placental pathology in the third trimester in these fetuses, and therefore the placental role in their growth and development remains unexplored. We performed quantitative morphometric analysis on the placentas of 18 fetuses with trisomy and ten normal control fetuses. Doppler umbilical artery analysis was performed on ten abnormal fetuses and all controls. The placentas of trisomic fetuses exhibited a significant reduction in small muscular artery count and small muscular artery/villus ratio. Abnormal Doppler waveforms correlated closely with reduced small muscular artery counts. Undervascularization and increased vascular resistance of the placenta of trisomic fetuses may contribute to diminished fetal growth. The placenta appears to be another fetal organ whose structure and function are affected adversely by abnormal karyotype.

Arterioles↗

Prolactin response to fentanyl in depression.

Ten unmedicated female inpatients with major depression (DSM-III) and 10 healthy volunteer women were given an intravenous injection of 0.1 mg fentanyl at 9:00 AM and 9:00 PM on different days. The prolactin secretory response to this opioid agonist was investigated for 1 h with serial blood sampling. Repeated measures Analysis of Variance yielded a significant effect of fentanyl administration on prolactin secretion (p less than 0.0001), and there were elevated hormone responses in the evening (p less than 0.005). No group difference was seen between healthy volunteers and depressed patients, but four of the depressives showed the most blunted response, and three of these low responders committed suicide within 1 year.

Adult↗

Cholecystectomy accompanying major abdominal surgery for gynecologic cancer.

In a 66-month period 950 major abdominal operations were performed for known or suspected gynecologic malignancy. Thirty-five patients (3.6%), of whom 29 had proven gynecologic malignancy, underwent cholecystectomy for cholelithiasis known from prior evaluation or found incidentally during abdominal exploration. All cholecystectomies were performed through the original incision with no direct operative morbidity or mortality. Cholecystectomy accompanying gynecologic cancer surgery appears to be well tolerated if performed expeditiously, and avoids the potential of postoperative cholecystitis in this select group of patients.

Adult↗

Multivariate analysis of monoamine indices in patients with chronic schizophrenia.

Levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid and serum levels of prolactin (PRL) and dopamine-beta-hydroxylase (DBH) were measured in 42 chronic schizophrenic inpatients grouped according to their scores on the Brief Psychiatric Rating Scale (BPRS) and the Abnormal Involuntary Movement Scale (AIMS). Factor analysis was carried out on various combinations of variables. In patients with tardive dyskinesia (TD), cerebrospinal fluid DA, DOPAC, HVA, NA, and serum DBH were distributed into three factors; in patients without TD, these substances were assembled in only one factor. Cerebrospinal fluid DA, DOPAC, and HVA were dispersed in two factors in patients with severe positive symptoms versus one factor in subjects with mild productive signs. Factor structures diverged only when the variables listed above were included in the analysis. These findings support the hypothesis that both the dopaminergic and the noradrenergic system contribute to TD and that positive schizophrenic symptoms are associated with dopaminergic dysregulation.

3,4-Dihydroxyphenylacetic Acid↗

Effect of adjuvant reserpine treatment on catecholamine metabolism in schizophrenic patients under long-term neuroleptic treatment.

The clinical and biochemical effects of adjuvant reserpine treatment were investigated in 12 chronic schizophrenic patients on long-term neuroleptic medication. The global severity of the symptoms using the Brief Psychiatric Rating Scale did not change significantly in the whole group, however, a moderate decrease in positive symptoms (factors though disturbance, activation and hostile-suspiciousness) was observed for 5 patients. Cerebrospinal fluid (CSF) noradrenaline levels showed a consistent decrease, but other biochemical parameters (CSF dopamine metabolites, platelet MAO and serum dopamine-beta-hydroxylase activities) did not change significantly. The changes of clinical symptoms and biochemical parameters did not show any correlation.

Adjuvants, Pharmaceutic↗

Diurnal variation in fentanyl-induced hormone responses and side effects.

The prolactin (PRL) and thyrotropin (TSH) secretory response to the opioid agonist fentanyl (0.1 mg IV) was investigated with serial blood sampling in ten healthy women at 9 AM and 9 PM on different days. In five subjects saline control trials were also performed. A repeated-measures analysis of variance yielded a highly significant effect of fentanyl administration both on PRL and TSH secretion. In every case there were elevated hormone responses in the evening, and more drug-related subjective symptoms were reported at this time than before noon. These findings indicate a diurnal variation of opioid responsiveness, with lower sensitivity in the morning.

Adult↗

Elevation of immunoreactive CSF TRH in depressed patients.

The concentration of thyrotropin-releasing hormone (TRH), a tripeptide (pyroglutamylhistidylprolin-amide), in the CSF of drug-free patients with DSM-III major depression, somatization disorder, and peripheral neurological disorders was measured with a sensitive and specific radioimmunoassay. The depressed patients had markedly higher CSF TRH concentrations than the other patient groups, and this finding could not be attributed to any demographic variables. The elevation of TRH in CSF provides further evidence of hypothalamic-pituitary-thyroid dysfunction in depression.

Adult↗

Changes in serum enzymes in moderate drinkers after an alcohol challenge.

When 14 "moderate" drinkers abstained from alcohol for four weeks, the activity of gamma-glutamyltransferase (GGT; EC 2.3.2.2) in their serum showed a large decrease. Immediately after the period of abstention, an orally given ethanol challenge of 1 g/kg produced a marked increase in serum GGT at 24 h, followed by a slow decline thereafter. Aspartate amino-transferase activity in serum was significantly increased at 24 h; however, alkaline phosphate, alanine aminotransferase, and lactate dehydrogenase showed much smaller or no changes. An abnormal increase in lactate dehydrogenase isoenzyme 5 was observed in seven subjects. In some of the moderate drinkers, liver biopsies showed mild chronic hepatitis or nonspecific changes. Eight nondrinking controls showed only slight increases in serum GGT following the same alcohol challenge; results for the other enzyme tests were unchanged. We consider it probable that pre-existing liver disease affects the response to ethanol, so that greater amounts of GGT are released from hepatic tissue; alternatively, drinkers may have a higher GGT activity in this tissue as a result of enzyme induction by ethanol. The alcohol challenge test was an effective discriminator between moderate drinkers and abstainers.

Adult↗

Ureteral injuries in an obstetrics and gynecology training program: etiology and management.

Between July 1980 and September 1987, 3185 major gynecologic operations were performed in our residency program. Ureteral injury occurred in 17 cases, 14 of which (0.4%) were accidental. In 16 cases, the injury was noted intraoperatively and repaired primarily; one injury was repaired after identification on the fourth postoperative day. Large pelvic masses, which limited exposure, and tumor invasion of the parametrium contributed to ureteral injury. Preoperative intravenous pyelogram or computed tomography did not prevent ureteral damage. Sixteen ureteroneocystostomies were performed with good result. One ureteroureterostomy leaked, but healed over a percutaneous stent without problems. All patients subsequently had normal renal function.

Aged↗

Multiple hormonal responses to morphine: relationship to diagnosis and dexamethasone suppression.

Plasma cortisol, prolactin (PRL), growth hormone (GH), and thyroid stimulating hormone (TSH) responses to intravenous morphine (0.1 mg/kg body weight) were investigated in five healthy women and 22 female psychiatric inpatients (eight with major depression, 12 with schizophrenia and two with personality disorders) during a 120 min period. The results were also related to a subsequent dexamethasone suppression test (DST). Morphine caused a strong and progressive decline in plasma cortisol which was uniform in controls, depressed, and nondepressed patients. DST nonsuppressors had significantly higher cortisol levels during the entire period, but the same response to morphine. Morphine strongly stimulated PRL secretion, which was found to be significantly smaller in patients than in controls, but no difference was seen between depressed and nondepressed subjects. GH and TSH showed only minor and variable changes after morphine, with no overall significant differences. The data in this study do not support the assumption of a major alteration in opiate receptor responsivity either in depression or in DST nonsuppressor patients insofar as the regulation of the adrenal, thyroid, GH and PRL hormone secretion is concerned.

Adult↗

CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia.

To further investigate the hypothesis that hyperactivity of the hypothalamic-pituitary-adrenal axis in patients with depression may be mediated by hypersecretion of corticotropin-releasing factor (CRF), the authors measured CRF-like immunoreactivity in CSF samples from 138 neurological control, 54 depressed, and 27 nondepressed (23 schizophrenic and four manic) subjects. The CSF CRF concentration was markedly higher (almost twofold) in depressed patients than in control subjects and nondepressed psychiatric patients. The concentration of CSF CRF was slightly but significantly higher in schizophrenic patients than in control subjects. These findings provide further support for the hypothesis that CRF hypersecretion occurs in major depression.

Adult↗