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Biomedical subjects

S Schlegel

Publications and source records attributed to S Schlegel.

At least 19 recordsLinked to original sources
PubMed2000

Epidural sufentanil during paediatric cardiac surgery: effects on metabolic response and postoperative outcome.

The metabolic and neuroendocrine effects of caudal epidural analgesia were studied during paediatric cardiac surgery. Combined epidural and general anaesthesia (EPI group; n=12) was compared with deep opioid anaesthesia (DOA group; n=12). During anaesthesia and surgery, haemodynamic stability was similar in the two groups. There was no significant difference between groups concerning the metabolic response to surgery but circulating catecholamines were significantly lower in the EPI group during and after surgery. Perioperative release of IL-6 was higher in the EPI group possibly reflecting a longer aortic clamp time. Incidence of postoperative life-threatening dysrhythmias was very low in the two groups. No significant reduction of postoperative mechanical ventilation, intensive care unit or hospital stays was reported with epidural analgesia. The incidence of postoperative infections was higher than expected in the two groups because of the poor properative clinical status of most of the children included in the study.

Analgesia, Epidural↗
PubMed1999

Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic.

RATIONALE: EMD 57445 (panamesine) is a high affinity sigma ligand with the profile of an atypical antipsychotic in animal studies. It has been reported recently to have antipsychotic activity in schizophrenia. However, its metabolite, EMD 59983, binds also to D(2) and D(3) dopamine (DA) receptors. OBJECTIVES: The aim of this study was to test, using single photon emission computed tomography (SPECT) and [(123)I]iodobenzamide (IBZM) as the radiotracer, whether EMD 59983 would pass the blood-brain barrier and to what extent it would contribute to the effects of EMD 57445 in schizophrenia. METHODS: Two IBZM SPECT-scans were performed in five neuroleptic-free schizophrenic patients (DSM IV), one before and one after treatment with 60 mg panamesine daily for a treatment duration of 12-26 days. RESULTS: A high occupancy of striatal D(2)-like DA receptors similar to that induced by typical neuroleptics was observed in all patients treated with EMD 57445. CONCLUSIONS: Our results suggest that a possible antipsychotic activity of EMD 57445 in schizophrenia is not necessarily attributable to its affinity for sigma receptors, but could be simply due to the potent antidopaminergic effects of EMD 59983, its main metabolite.

Adult↗
PubMed1999

Addition of low-dose fluvoxamine to low-dose clozapine monotherapy in schizophrenia: drug monitoring and tolerability data from a prospective clinical trial.

Combining fluvoxamine and clozapine may be a strategy to improve therapeutic effects on negative symptoms in schizophrenic patients. Fluvoxamine, however, markedly inhibits the metabolism of clozapine, and hazardous side effects may result. This study prospectively investigated the safety and tolerability of an add-on therapy with fluvoxamine to a clozapine monotherapy in schizophrenic patients. Sixteen schizophrenic patients received 50 mg fluvoxamine as a comedication after having reached steady-state conditions under clozapine monotherapy. Patients were monitored for subjective adverse events, laboratory parameters, EEG and ECG recordings, orthostatic hypotension and their psychopathology. Concomitantly, serum concentrations of clozapine and metabolites were measured during monotherapy and after addition of fluvoxamine. In all patients, the serum concentrations of clozapine and metabolites were markedly increased (average: 2-3 fold, up to 5 fold for clozapine) after addition of fluvoxamine. Side effects remained almost unchanged in frequency and severity in spite of the pharmacokinetic interactions. ECG or laboratory parameters and orthostatic tests were similar under monotherapy and comedication. Minimal increases of EEG abnormalities were observed, but they were not associated with clinical impairment. Epileptic activities were always absent. The psychopathology improved which continued after start of the comedication. Though the addition of fluvoxamine to clozapine medication was well tolerated and critical side effects were absent, the combined treatment should be controlled by drug monitoring, as serum concentrations of clozapine increased to unpredictably high levels. Further studies have to find out if the combined treatment could be advantageous to clozapine monotherapy.

Adolescent↗
PubMed1999

Randomised placebo-controlled trial of moclobemide, cognitive-behavioural therapy and their combination in panic disorder with agoraphobia.

BACKGROUND: In the treatment of panic disorder with agoraphobia, the efficacy of pharmacological, psychological and combined treatments has been established. Unanswered questions concern the relative efficacy of such treatments. AIMS: To demonstrate that moclobemide and cognitive-behavioural therapy (CBT) are effective singly and more effective in combination. METHOD: Fifty-five patients were randomly assigned to an eight-week treatment of: moclobemide plus CBT; moclobemide plus clinical management ('psychological placebo'); placebo plus CBT; or placebo plus clinical management. RESULTS: Comparisons between treatments revealed strong effects for CBT. Moclobemide with clinical management was not superior to placebo. The combination of moclobemide with CBT did not yield significantly better short-term results than CBI with placebo. The CBT results remained stable during a six-month follow-up, although a substantial proportion of patients treated with placebo plus CBT needed additional treatment. CONCLUSIONS: CBT was highly effective in the treatment of panic disorder with agoraphobia and reduced agoraphobia to levels that were comparable to those of non-clinical controls.

Adolescent↗
PubMed1998

Combination treatment with clozapine and paroxetine in schizophrenia: safety and tolerability data from a prospective open clinical trial.

Clozapine is a drug with many side effects, some of them with potentially hazardous outcome (e.g. seizures, agranulocytosis), if not carefully monitored. It has been shown that the metabolism of clozapine may be affected by concomitant treatment with selective serotonin reuptake inhibitors (SSRIs), while there have been reports of improved efficacy on negative symptomatology of clozapine in combination with SSRIs. Therefore, this prospective open clinical trial was performed to investigate the safety and tolerability of the coadministration of clozapine and paroxetine under control of serum concentrations of clozapine and its metabolites and the effect of this combination treatment on psychopathological outcome was evaluated. A total of 14 patients suffering from schizophrenia or schizodepressive disorder with predominant negative symptomatology were included. The duration of the study was at least 6 weeks for each patient. Initial treatment was a monotherapy with clozapine at a daily dose of 2.5 mg/kg weight. After two measurements of serum concentrations of clozapine and metabolites during steady state conditions, an add-on therapy with 20 mg paroxetine was initiated. No concomitant medication was allowed. The main finding of our prospective study was that addition of paroxetine to a monotherapy with clozapine was a well tolerated medication that did not give rise to new clinically relevant side effects. After addition of paroxetine the serum concentrations of clozapine and its major metabolites remained virtually constant. The results of the psychopathological measurements indicated a further clinical improvement, although the small open study could not test for efficacy.

Adult↗
PubMed1997

[123I]IBZM SPECT in patients treated with typical and atypical neuroleptics: relationship to drug plasma levels and extrapyramidal side effects.

[123I]Iodobenzamide (IBZM) is an iodine-labeled dopamine receptor ligand and can be used to visualize brain D2 receptors in humans with single photon emission computerized tomography (SPECT). The ratio of striatal IBZM uptake to uptake in frontal cortex (ST/FC ratio) represents a semiquantitative measure of D2 receptor binding in the striatum. Our study sample included six patients treated with haloperidol (3.0-8.0 mg/day orally; one patient with an average of 0.9 mg/day intramuscularly), five patients with benperidol (9.0-15.0 mg/day orally) and nine patients treated with clozapine (200.0-600.0 mg/day orally). Typical neuroleptics (TNs) and atypical neuroleptics (ANs) were significantly different in their ST/FC ratios. The ST/FC ratios indicated that patients treated with benperidol exhibited the lowest ST/FC ratios, with increasingly higher ratios in patients on haloperidol or clozapine. We found a curvilinear relationship between the ST/FC ratios and the dose/kg body wt. of TNs and ANs on the basis of a dose-normalization according to Ki-values of the neuroleptic at D2 receptors and a weaker, but also curvilinear relationship between ST/FC ratios and normalized dosages according to clinically defined chlorpromazine equivalents. The specific uptake of IBZM did not correlate with the plasma levels of the TN haloperidol at the present dose range (0-12.4 ng/ml). For clozapine, a meaningful negative correlation between plasma levels and ST/FC ratio could be established. There was a negative continuous correlation between uptake of IBZM and extrapyramidal side effects, which is different from the threshold-based relationship between extrapyramidal side effects and IBZM uptake reported previously.

Adult↗
PubMed1997

Proton magnetic resonance spectroscopy in dementia of Alzheimer type.

Reduced N-acetyl aspartate (NAA) and increased myo-inositol (MI) levels have been reported in patients with dementia of Alzheimer type (DAT) in comparison with controls. We wished to assess the validity of these findings and to evaluate possible correlations of metabolite proportions with cognitive dysfunction in DAT. Twelve patients with DAT and 10 healthy age-matched controls were included. The severity of dementia was assessed using different scales including the Mini-Mental State Examination. MRS was performed with a conventional 1.5 Tesla scanner in a single voxel in the centrum semi-ovale (TE = 30 ms or TE = 136 ms; TR = 1500 ms). The evaluation of MRS results was limited by low interrater, intermeasurement (different echo times) and test-retest reliabilities, by a high interindividual variance and by the failure to measure absolute metabolite concentrations. These problems in mind, it was remarkable that previously reported reductions of NAA levels in patients with DAT could be reproduced in the present sample. The proportion of NAA was diminished in demented subjects in comparison with controls (37% vs 44.90%, short TE). A non-significant trend towards minor reductions of creatine, choline and MI proportions in these subjects might indicate that proportions of other metabolites necessarily increase when NAA is reduced. Cognitive dysfunction of demented subjects was significantly correlated with reductions of NAA, but not with increases of MI. Due to the present technical and methodological problems and to the non-specificity of findings, proton MRS cannot be applied to support the diagnosis of DAT in a clinical setting.

Aged↗
PubMed1997

[Value of computerized tomography and magnetic resonance tomography in psychiatric diagnosis].

This paper evaluates the role of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of psychiatric disorders according to the "International Classification of Diseases" (ICD-10). Indications for CT/MRI can be derived from ICD-10 for the identification or exclusion of defined cerebral lesions resp. for the etiology in organic disorders. Due to the lack of specific morphological findings, CT/MRI do not contribute to the classification of all other diagnoses. CT/ MRI can only exclude causal organic factors. However, ICD-10 provides only few guidelines for ruling out cerebral pathology (e.g. tumors in bulimic anorexia). Therefore, recommendations for routine CT/MRI-investigations for the exclusion of organic disorders are required and might be developed by the quality assurance. Application of CT or MRI: CT plays an important role in diagnostic imaging in routine as well as in emergency situations (haemorraghe, hamatoma, infaction, head injury, tumour, vascular malformation). MRI on the other hand, is more sensitive in the diagnosis of inflammatory diseases, skull base lesions, degenerative changes of the white matter and in the imaging of hydrocephalus and epilepsy.

Brain↗
PubMed1996

Expression of alpha subunit genes of nicotinic acetylcholine receptors in human lymphocytes.

Using immunohistochemistry and in situ hybridisation, we have studied whether alpha-subunits of nicotinic acetylcholine receptors (nAChRs) are expressed in human lymphocytes. Cells were isolated by differential low speed gradient centrifugation from heparinised venous blood of 10 healthy volunteers. Receptor sites were visualised using the monoclonal antibody WF6 which specifically recognises alpha-isoforms from several species including man. For visualisation of transcripts, digoxigenin-labelled cRNA probes for alpha 4- and alpha 3-subunits were used. Immunostaining revealed specific binding of WF6 to isolated human lymphoid cells. The antibody was bound to most cells and concentrated preferentially in the perinuclear/surface region. The immunoreactivity resembled that observed after application of an antibody recognising CD4 surface proteins which was conducted for comparison. In situ-hybridisation revealed that the alpha 4-subunit genes of nAChRs was expressed in lymphocytes of all probands. The alpha 3-subunit was found, with lower intensity than alpha 4-transcripts, in eight of the 10 individuals. Control incubations with corresponding sense cRNAs were negative. It is concluded that human lymphocytes are able to express alpha-subunit genes of nAChRs.

Adult↗
PubMed1996

Prolactin plasma levels and D2-dopamine receptor occupancy measured with IBZM-SPECT.

By the application of 123([123I]IBZM), an iodine-labelled dopamine D2-receptor antagonist, brain D2 receptors in humans can be visualized with single photon emission computed tomography (SPECT). The ratio of IBZM binding to striatal regions versus binding to frontal cortex (ST/FC ratio) provided a semiquantitative measurement of D2 receptor binding in the striatum. This study investigated the relationship between receptor occupancy and plasma prolactin levels in 12 male patients treated with haloperidol, benperidol or clozapine. Prolactin levels were positively correlated with D2 receptor occupancy, reflecting at least in part a comparable dopamine receptor antagonism in different dopaminergic pathways.

Adult↗
PubMed1995

D2-receptor imaging with [123I]IBZM and single photon emission tomography in psychiatry: a survey of current status.

D2-dopamine receptors can be visualized in the human brain in vivo by Single Photon Emission Tomography (SPECT) and the radiolabeled benzamide [123I]IBZM. The present paper reviews the current status of this type of functional brain imaging with respect to basic methodological aspects, data analysis and quantification. The results from published clinical studies in different psychiatric patient populations and normal controls with [123I]IBZM are reviewed. [123I]IBZM-SPECT is a powerful tool for the investigation of D2-dopamine receptor status in psychiatric disorders, different types of drug treatment as well as therapeutic and side effects of pharmacologic agents. However, there still is a need for standardized imaging times and image-processing procedures. Advantages and disadvantages of SPECT with special regard to Positron Emission Tomography (PET) are also discussed.

Benzamides↗
PubMed1995

Seroquel (ICI 204 636), a putative "atypical" antipsychotic, in schizophrenia with positive symptomatology: results of an open clinical trial and changes of neuroendocrinological and EEG parameters.

Preclinical data indicated that seroquel (ICI 204 636), a dibenzothiazepine with 5-HT2 and D2-like receptor antagonistic properties, might be an effective antipsychotic agent, causing fewer extrapyramidal side effects than typical neuroleptics. In the present study, 12 patients suffering from schizophrenia or schizophreniform disorder with predominantly positive symptomatology were treated in an open clinical trial for 4 weeks with seroquel at a maximum dosage of 750 mg/day. The drug was generally well tolerated, and virtually no adverse extrapyramidal side effects such as acute dystonia, parkinsonism or akathisia were observed. Total scores for BPRS (item score 0-6; baseline: 42.0 +/- 2.3; mean +/- SEM), SAPS (64.5 +/- 4.8) and SANS (55.0 +/- 4.3) showed a moderate decrease at the end of treatment (BPRS: 30.0 +/- 3.5; SAPS: 36.1 +/- 6.7; SANS: 42.5 +/- 5.9), when intention-to-treat analysis was applied. There were considerable interindividual differences in treatment response, with some subjects showing almost full remission of positive symptoms, in contrast to about half of the patients who showed no satisfactory clinical improvement. Interestingly, patients showing good antipsychotic response reported slight initial side effects like mild sedation. Prolactin and TSH levels were not altered during seroquel administration. As to pharmaco-EEG investigations, seroquel caused a moderate increase of the absolute power in the alpha, theta, and beta frequency bands, paralleled by a decrease of delta activity. There were no signs of paroxysmal EEG activity under seroquel.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Decreased benzodiazepine receptor binding in panic disorder measured by IOMAZENIL-SPECT. A preliminary report.

Single photon emission tomography (SPECT) imaging of the central benzodiazepine receptor (BZr) became possible with the newly developed ligand 123I-IOMAZENIL. The BZr binding was investigated in ten patients with panic disorder (PP) compared to ten epileptic patients (EP). Panic patients had lower IOMAZENIL uptake rates in the frontal, occipital and temporal cortex than EP indicating the involvement of the BZr complex in panic disorder.

Adult↗
PubMed1994

[Quality assurance in nursing: nursing standard. Nausea, gagging and vomiting during emetogenic cytostatic therapies. Report of research into the development and introduction of nursing standards].

This report documents the introduction of standard-setting in the haemato-oncological reverse-isolation unit of the Kanton hospital, Basle. The topic is the prevention or reduction of nausea, choking and vomiting, and the treatment of patients who are receiving prolonged chemotherapy. The objective was quality assurance in nursing care. The definition of the desired outcome was the well-being and safety of patients. In addition the wish of the staff to increase their security in dealing with antiemetics was taken into consideration. The authors describe the basic problems they encountered in their strategies and actions for standard setting. By extensive use of measurement and evaluation it was possible, in cooperation with medical leadership, to develop instructional leaflets and checklists. Approximation to the intended outcome was achieved. The well being of patients and satisfaction of the safety-needs of staff and patients reached a high level. The report shows that the introduction of nursing standards requires great effort and a high level of commitment of the entire team. It also shows that the effort is worthwhile for patients and staff.

Antineoplastic Agents↗
PubMed1992

Relationships between psychomotor retardation and EEG power spectrum in major depression.

In 63 depressed patients, the associations between severity of depression, psychomotor retardation, assessed by the Bech-Rafaelsen Melancholia Scale, and EEG spectral analysis were examined. Slow EEG activity (theta 2/alpha 1 bands) was positively and fast activity (alpha 3/beta bands) negatively correlated with the observed retardation. Out of the four retardation subitems (motor, verbal, intellectual and emotional), motor retardation was closest correlated with slow EEG activity.

Adult↗
PubMed1991

Latencies of the P300 component of the auditory event-related potential in depression are related to the Bech-Rafaelsen Melancholia Scale but not to the Hamilton Rating Scale for Depression.

The relationship between severity of depression and the P300 latency of auditory event-related potential was investigated in 36 patients with a major depressive episode according to DSM-III. Positive correlations were found between of the P300 latency and the total score of the Bech-Rafaelsen Melancholia Scale (BRMS), the 4 retardation items of the BRMS (motor, verbal, intellectual and emotional) and the item for lowered mood. In contrast, latencies were not associated with the scores of the Hamilton Rating Scale for Depression, which considers retardation to a lesser extent than the BRMS.

Adult↗
PubMed1991

Early undifferentiated connective tissue disease. II. The frequency of circulating antinuclear antibodies in patients with early rheumatic diseases.

The presence of antinuclear antibodies (ANA) in the serum is a common finding in various connective tissue disorders, but usefulness of these antibodies in making diagnoses or prognoses is not known. We report the results of a panel of ANA determinations including ANA, anti-dsDNA, Sm, RNP, SSA, SSB, Jo-1, Scl-70 and PM-1 in 410 patients in a 5-year descriptive study of 410 patients with rheumatic disease symptoms of less than one year's duration. While some patients met diagnostic criteria for a specific rheumatologic diagnosis, others were classified as undifferentiated connective tissue disease (UCTD) and were subclassified by a constellation of symptoms. Our results show that ANA is sensitive in systemic lupus erythematosus (SLE) and progressive systemic sclerosis even in early disease but is not specific. Other "specific" autoantibodies were seen most frequently in SLE but were relatively insensitive and were seen in low frequency in UCTD. ANA have limited diagnostic value in patients with early disease. The prognostic value of these tests will be assessed as the prospective study of these cohorts progresses.

Antibodies, Antinuclear↗