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Biomedical subjects

I Degrell

Publications and source records attributed to I Degrell.

At least 19 recordsLinked to original sources
PubMed2004

The role of cytochrome P450 enzymes in the metabolism of risperidone and its clinical relevance for drug interactions.

In the recent years it has been increasingly recognized that pharmacogenetical factors play an important role in the drug treatment. These factors may influence the appearance of side-effects and drug interactions due to interindividual differences in the activity of metabolizing enzymes. Risperidone in humans is mainly metabolized to 9-hydroxyrisperidone by the polymorphic cytochrome enzyme P450 2D6 (CYP2D6). Plasma concentrations of risperidone and 9-hydroxyrisperidone show large interindividual variability, which may be partly related to the activity of the CYP2D6 enzyme. Around seven percent of Caucasians have a genetically inherited impaired activity of the CYP2D6 enzyme. Debrisoquine metabolic ratio (a marker of CYP2D6 activity) and the number of CYP2D6 active genes have been related to risperidone plasma concentrations among patients during steady-state conditions. A large number drugs have been described to be metabolized by CYP2D6, and it is therefore important to evaluate the clinical significance of the impaired metabolism and possible drug interactions on the enzyme. Since risperidone/9-hydroxyrisperidone ratio strongly correlates with CYP2D6 enzyme activity and the number of CYP2D6 active genes, thus it might be a useful tool in clinical practice to estimate the possible risk of drug interactions due to impaired CYP2D6 enzyme activity. CYP3A4 is the most abundant drug metabolizing enzyme in humans, and in vitro and in vivo results suggest also a role for the enzyme in risperidone metabolism. The consideration of the implication of cytochrome P450 enzymes in risperidone metabolism may help to individualize dose schemes in order to avoid interactions and potentially dangerous side-effects, such us QTc interval lengthening among patients with cardiac risk factors.

Chromatography, High Pressure Liquid↗
PubMed2002

Relationship between risperidone and 9-hydroxy-risperidone plasma concentrations and CYP2D6 enzyme activity in psychiatric patients.

The implication of cytochrome P450 CYP2D6 enzyme activity in the metabolism of the antipsychotic drug risperidone has been reported in vitro and in studies of healthy volunteers. Around 7 % of Caucasians have inherited impaired capacity of this enzyme (poor metabolisers). These subjects might be prone to higher plasma concentrations of risperidone. The aim of the study was to determine the relationship between the debrisoquine metabolic ratio (MR), a marker of CYP2D6 enzyme activity, and risperidone plasma levels in psychiatric patients. A population of 40 Spanish and Hungarian schizophrenic patients was studied. The possible inhibition of CYP2D6 enzyme was also evaluated in a subgroup of patients co-medicated with inhibitors of CYP2D6. The risperidone/9-hydroxy-risperidone ratio correlated significantly with debrisoquine MR (p < 0.001). In patients co-medicated with strong inhibitors of CYP2D6, the plasma levels of risperidone (p < 0.05) and debrisoquine MR (p < 0.01) and risperidone/9-hydroxy-risperidone ratio were higher compared to patients with monotherapy. According to the present data, the evaluation of the risperidone/9-hydroxy-risperidone ratio may reflect the actual enzyme activity of CYP2D6. Therefore, the use of this ratio may help to assess potential pharmacokinetic interactions and to improve risperidone treatment.

Adult↗
PubMed2000

Clozapine withdrawal symptoms after change to sertindole in a schizophrenic patient.

A 30-year-old male patient with paranoid schizophrenia was on clozapine therapy for more than five years. Discontinuation of clozapine and an attempt to change his medication to sertindole has led to serious psychotic and somatic symptoms. After readministration of clozapine the psychotic symptoms rapidly disappeared. The patient was monitored by BPRS and PANSS positive and negative scale. Also clinical and labor parameters of the patient were monitored. The change of his medication from clozapine to sertindole was unsuccessful. This case report suggests that although atypical antipsychotics may be generally different from the classical neuroleptic drugs, there are also significant differences among the atypical antipsychotic drugs in their effects on the receptors of the central nervous system. Therefore the change of clozapine to another atypical antipsychotic medication in the clinical practice should be cross-tapered and the symptoms of withdrawal closely monitored.

Adult↗
PubMed1997

[First Hungarian experiences with positron emission tomography (PET) studies. Members of the PET working group].

Diagnostic investigations commenced on the 28th of June 1994 in Hungary's and Central Europe's first PET Centre at the University Medical School of Debrecen. The Centre is equipped with a GE 4096 Plus whole body PET scanner. A metabolic tracer, 18F-deoxy-D-glucose (FDG), was used in the investigations. During the first 15 months 249 PET investigations were made in the Centre of which 242 were diagnostic and 7 normal subjects served as control for the patient studies with brain scans. The number of oncological indications (intra- and extracranial tumours, Hodgkin's lymphomas) was n = 105 (43.4% of the 242 diagnostic examinations), neurological investigations (without intracranial tumours) formed the dominant group (n = 117; 48.3%), whereas the number of cardiological indications was 20 (8.3%). The oncological studies included those of intracranial tumours (n = 76; 31.4%); thyroid tumours (n = 9; 3.7%); Hodgkin's lymphomas (n = 7; 2.9%) and other extracranial tumours (n = 13; 5.4%). The distribution of different neurological and psychiatric investigations was as follows: localization of focal epileptogen zone (n = 60; 24.8%); differential diagnosis of dementias (n = 30; 12.4%); exploration of cerebrovascular diseases (n = 10; 4.1%); and other neurological diseases (n = 17; 7.0%). The main objective of the cardiological PET investigations was the exploration of viable myocardium. The present paper overviews both the procedures (including administrative issues, as well) and the results of the first 249 FDG-PET investigations.

Aged↗
PubMed1990

Concentration gradients for HVA, 5-HIAA, ascorbic acid, and uric acid in cerebrospinal fluid.

Concentrations of HVA, 5-HIAA, ascorbic acid, and uric acid in the lumbar and cisternal cerebrospinal fluid (CSF) were measured in psychiatric and neurologically impaired patients. The concentration of HVA is 6.1 times and of 5-HIAA 2.7 times higher in cisternal than in lumbar samples, the cisternal level of uric acid is half that of the lumbar region, but no significant differences were found in ascorbic acid concentrations. Correlation between lumbar and cisternal metabolite concentrations is high for 5-HIAA and ascorbic acid, and is less for HVA and uric acid. In cisternal CSF there is a significant correlation between levels of HVA-5-HIAA, 5-HIAA-ascorbic acid, and 5-HIAA-uric acid. These correlations disappear in lumbar CSF. These findings indicate that extrapolations to cisternal neurotransmitter metabolite concentration from lumbar measures are unwarranted for HVA, but not for 5-HIAA.

Adult↗
PubMed1989

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↗
PubMed1988

Purine metabolites in the CSF in presenile and senile dementia of Alzheimer type, and in multi infarct dementia.

Concentrations of hypoxanthine, xanthine, uric acid and creatinine were measured in CSF of patients suffering form presenile and senile dementia of Alzheimer type (PDAT, SDAT) and multi infarct dementia (MID) and in a reference group of young neurotic patients. There was no difference in hypoxanthine concentration, but there was a marked elevation of xanthine concentration in each dementia group, independent of the type of dementia. There was a significant elevation of uric acid in SDAT and MID but not in PDAT. The concentration of uric acid was higher in MID than in SDAT. There was a higher level of creatinine in the dementia groups, but no difference was seen among the dementia groups. These results are discussed in order to better interpret the etiology and the differentiated diagnosis of the types of dementia.

Adolescent↗
PubMed1988

Hypoxanthine, xanthine, urate and creatinine concentration gradients in cerebrospinal fluid.

The purine metabolites hypoxanthine, xanthine and urate as well as creatinine were measured in cerebrospinal fluid (CSF) from two groups of patients and a reference sample group. In one of the patient groups lumbar CSF was collected in 2 ml portions until a total volume of 14 ml was withdrawn. Every second portion was analysed for its content of the metabolites in focus. In the other patient group both cisternal CSF and a fixed volume (20 ml) of lumbar CSF were obtained and analysed. An increase in concentration of hypoxanthine, xanthine and creatinine and a decrease in urate concentration was found in the successive CSF specimens. The mean individual increase in hypoxanthine concentration between the first and the last 2 ml portion was as high as 39.6%, while it was lower for xanthine, 21.5%, and creatinine, 6.7%. The decrease in urate concentration was 17.2%. The results from the other patient group were in good agreement with these findings. The concentrations in the cisternal CSF was 162% of that in lumbar CSF for hypoxanthine, 155% for xanthine, 123% for creatinine and 80% for urate. Mechanisms behind inter- and intraindividual differences in gradients are discussed.

Biological Transport, Active↗
PubMed1985

Dementias, psychological tests, and neurotransmitters.

A preliminary investigation was made of data of intelligence quotient, dementia quotients, objective profile analysis of MAWI (Hungarian standardized version of WAIS) in patients suffering from multi infarct, primary degenerative and alcoholic dementia (MID, PDD, Alc. D). Homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) were measured in lumbar cerebrospinal fluid (CSF) from patients with presenile dementia and senile dementia of Alzheimer's type (PDAT and SDAT) and multi infarct dementia. They were compared to controls and to each other. Alcoholic dementia can be differentiated from other types of dementia mainly by the values of verbal and practical quotients (VQ/PQ), Hewson Index 5 and by the objective profile analysis. MID can hardly be differentiated from PDD, but the objective profile analysis can help, mainly subtests 1 and 3 of MAWI. No decrease was found in the concentrations of HVA and 5-HIAA in lumbar CSF of demented patients compared to controls, but there was an elevation in 5-HIAA concentration.

Aged↗
PubMed1983

Monoamine metabolites in the CSF of conscious unrestrained cats.

The dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured repeatedly over a period of up to 5 months at different sites of the brain ventricular system in unrestrained, awake cats. Samples of 10 microliter CSF were analyzed by high pressure liquid chromatography and subsequent electrochemical detection. Concentrations were in the range of 30-130 ng/ml for DOPAC, 110-340 ng/ml for 5-HIAA and 180-750 ng/ml for HVA. The monoamine metabolites were constant even over a period of several months if measured in the same animal but there was a marked interindividual variation. A marked gradient for monoamine metabolites was found when CSF samples from frontal sites of the lateral ventricle were compared to CSF samples from the dorsal lateral ventricle. The concentrations of DOPAC and HVA were higher at frontal sites.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Aspiration cytology of breast carcinoma.

In the past 12 years aspiration cytological examination was carried out in 310 cases of histologically verified breast cancer. A classification of mammary carcinomas is presented and the cytomorphological features of cells constituting the different types of tumour are described. The value of aspiration cytology in preoperative diagnosis of early cancerous proliferations is emphasized. In the light of clinical, mammographic and cytological investigations the accuracy is about 96%. The method is reliable, quick, has no hazard, and can be performed in out-patients. Its routine application is recommended to all institutions possessing adequate facilities and staff.

Adenocarcinoma↗