Biomedical subjects

S Ulrich

Publications and source records attributed to S Ulrich.

At least 55 records · Page 3Linked to original sources

PubMed1999

Detection of two novel porcine herpesviruses with high similarity to gammaherpesviruses.

Evidence for the existence of porcine gammaherpesviruses was obtained by PCR and sequence analysis. Initially, samples of peripheral blood mononuclear cells (PBMC), spleens, lungs, kidneys and livers of pigs from Germany and Spain were tested with a PCR assay which targets conserved regions of the herpesvirus DNA polymerase gene with degenerate and deoxyinosine-substituted primers. Amplicons of identical sequence were obtained from one spleen and two PBMC samples. This sequence showed a high percentage of identity with the DNA polymerase genes of herpesviruses of the oncogenic subfamily Gammaherpesvirinae. Alignment of amino acid sequences showed the highest identity values with bovine gammaherpesviruses, namely alcelaphine herpesvirus type 1 (68%), ovine herpesvirus type 2 (68%) and bovine lymphotropic herpesvirus (67%). Comparison with pseudorabies virus and porcine cytomegalovirus, which are the only porcine herpesvirus species presently known, showed values of only 41%. PCR analysis of PBMC (n = 39) and spleen (n = 19) samples from German pigs, using primers specific for the novel sequence, revealed a prevalence of 87 and 95%, respectively. In this analysis, three out of eight spleen samples from Spanish pigs were also positive. Subsequent sequencing of the amplicons revealed the presence of two closely related gammaherpesvirus sequences, differing from each other by 8% at the amino acid level. The putative novel porcine herpesviruses, from which these sequences originated, were tentatively designated porcine lymphotropic herpesvirus type 1 and type 2 (PLHV-1 and PLHV-2). When using pig organs for xenotransplantation, the presence of these viruses has to be considered.

Amino Acid Sequence↗

PubMed1999

Decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia: investigation of in vivo benzodiazepine receptor binding.

OBJECTIVES: Catatonia is a psychomotor syndrome with concomittant akinesia and anxiety which both respond almost immediately to benzodiazepines such as lorazepam. The benzodiazepine receptor distribution was therefore investigated in akinetic catatonia with single photon emission tomography (SPECT) using iodine-123-iomazenil ((123) I Iomazenil). METHODS: Ten akinetic catatonic patients, 10 psychiatric controls (similar age, sex, medication, and underlying psychiatric diagnosis but without catatonic syndrome), and 20 healthy controls were investigated with SPECT 2 hours after injection of (123) I Iomazenil. To exclude potential effects of cerebral perfusion (r-CBF) r-CBF was additionally investigated with Tc-99mECD SPECT. RESULTS: Catatonic patients showed significantly lower iomazenil binding and altered right-left relations in the left sensorimotor cortex compared with psychiatric (p<0.001) and healthy (p<0.001) controls. In addition, there was significantly lower r-CBF in the right lower prefrontal and parietal cortex in catatonia whereas in the left sensorimotor cortex no differences in r-CBF between groups were found. Catatonic motor and affective symptoms showed significant correlations (p<0.05) with benzodiazepine binding in the left sensorimotor cortex as well as with right parietal r-CBF. CONCLUSIONS: Reduced iomazenil binding suggests decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia. In addition to reduced GABA-A receptor density in the left sensorimotor cortex the parietal cortex seems to be involved in pathophysiology of catatonic symptoms. It is concluded that, considering results from correlation analyses, both emotional and motor symptoms in catatonia seem to be closely related to left sensorimotor and right parietal alterations.

Adult↗

PubMed1998

Multi-anode detection in electrospray ionization time-of-flight mass spectrometry.

An electrospray ionization ion source coupled to a time-of-flight mass analyzer incorporating a multi-anode time-to-digital converter is described. High-speed data acquisition (kHz mass spectral acquisition) rates are achieved. The four-anode detector produces a significant increase in detection/counting efficiency over that for a single-anode detector. In this work a 2.5 times increase in detection efficiency is demonstrated. The multi-anode detector is also used as a diagnostic tool to optimize transmission of the ion optics.

Cytochrome c Group↗

PubMed1998

Nanoparticle technology for delivery of drugs across the blood-brain barrier.

The Leu-enkephalin dalargin and the Met-enkephalin kyotorphin normally do not cross the blood-brain barrier (BBB) when given systemically. To transport these neuropeptides across the BBB they were adsorbed onto the surface of poly(butylcyanoacrylate) nanoparticles (NPs) and the NPs were coated with polysorbate 80. Central analgesia was measured by the hot plate test in mice. The antidepressant amitriptyline, which normally penetrates the BBB, was used to examine the versatility of the NP method. The concentration of amitriptyline in serum and brain of mice was determined by a gas chromatographic method. Furthermore, NPs were fabricated with different stabilizers. After the adsorption of the peptides on polysorbate 85-stabilized NPs, analgesia was noted after intravenous application when NPs were not coated. The amitriptyline level was significantly enhanced in brain when the substance was adsorbed onto the NP and coated or when the particles were stabilized with polysorbate 85.

Amitriptyline↗

PubMed1998

Therapeutic window of serum haloperidol concentration in acute schizophrenia and schizoaffective disorder.

Although several studies have been performed on the serum level-therapeutic effect relationship of neuroleptic drugs, the application of therapeutic drug-monitoring of neuroleptics is still a matter of controversy. Until now, haloperidol provided the most promising results. For this reason, an investigation of the dependence of clinical improvement on haloperidol serum levels was conducted in an acute psychiatric ward (Landeskrankenhaus Bernburg). In an open clinical trial haloperidol serum levels were measured in 57 acute schizophrenic patients for at least three weeks and correlated with clinical outcome (percent change of Brief Psychiatric Rating Scale, BPRS). A bisigmoidal model was used for data analysis. After three weeks of treatment, the major result proved to be a significant relationship between haloperidol serum level and therapeutic effect with pseudo-r2=0.316 and p=0.0031. Clinical improvement is enhanced by increasing haloperidol concentration up to about 10 ng/ml. It attains a maximum at about 10 ng/ml and decreases at haloperidol serum levels in a range of 10 ng/ml to 50 ng/ml. A simulation of this dependence of clinical improvement on serum levels, mediated by the variable dose design, can be excluded because of the results of a retrospective analysis of dosing behavior. Further evidence is thus provided for the dependence of therapeutic effect on the serum haloperidol concentration in acute schizophrenia. For practical application the position of a therapeutic window can be defined by a lower threshold level of about 5 ng/ml and an upper threshold of about 17 ng/ml. However, a maximal therapeutic effect is assured at 10 ng/ml. This should be the target value in serum level-guided dose adjustments.

Adult↗

PubMed1998

The relationship between serum concentration and therapeutic effect of haloperidol in patients with acute schizophrenia.

Haloperidol is the most commonly used antipsychotic drug in the therapy of acute schizophrenia. Clinicians have been using therapeutic drug monitoring in an attempt to improve clinical application of this drug. The scale of interest in this area is emphasised by the large number of studies (about 50) concerning the serum concentration-therapeutic effect relationship (SCTER) of haloperidol, including 35 studies on patients with acute schizophrenia. However, conflicting results concerning the existence and position of a therapeutic window have emerged. This article aims to provide a comprehensive review of the study design of studies in patients with acute schizophrenia before the study data are used for decision-making. For this purpose, a reproducible system for the evaluation of studies in this special area, a so-called total study score (TSS), was developed on an empirical basis. Thus, insufficient study design was found to be a reason for negative results. On the other hand, in spite of a great variability, the majority of studies with good design provided evidence for a significant SCTER: a bisigmoidal dependence of clinical effect on haloperidol serum concentration. The therapeutic effects of haloperidol increase at low concentrations, and the concentration has a maximum effect at about 10 micrograms/L and again decreasing at higher concentrations. The data of 552 patients also fit to this model in a single scatter plot (pseudo-r2 = 0.076, p < 0.001). The position of the therapeutic window was determined at about 5.6 to 16.9 micrograms/L. Patients treated with serum concentrations within this optimal range had a significantly better response compared with outside this range (p < 0.001, Student t-test). Therefore, a quantitative synthesis of all available data by means of effect-size analysis provides a mean effect-size (g) = 0.499 +/- 0.182 (standard deviation) for the comparison of haloperidol-treatment with serum concentrations within versus outside the therapeutic window. Thus, because of this moderate positive effect, serum concentration assay of haloperidol is recommended for patients with acute schizophrenia in a therapeutic drug monitoring programme. The modalities of haloperidol therapeutic drug monitoring in clinical practice are discussed, e.g. patient selection, method and time for serum concentration measurement, influence of premedication and comedication, interpretation of results and dose adjustment. Clinical investigations into this subject should focus on covariates which are responsible for the variability of the SCTER. Serum concentration assay is advised for investigations of nonresponse to exclude patients with pseudo-drug resistance.

Acute Disease↗

PubMed1997

Solid-phase microextraction with capillary gas-liquid chromatography and nitrogen-phosphorus selective detection for the assay of antidepressant drugs in human plasma.

Solid-phase microextraction (SPME) was tested as a sample preparation for the simultaneous assay of ten antidepressant drugs and metabolites (TADs) in human plasma. Aqueous NaOH (0.5 ml, 1 M) and chloramitriptyline (50 microliters, 40 micrograms/ml) as internal standard (I.S.) were added to a 2-ml plasma sample. This mixture was extracted with a 100-micron polydimethylsiloxane SPME fiber (Supelco) for 10 min. After washing in water and methanol (50%) and subsequent drying at room temperature, desorption of the fiber was performed in the injection port of a gas chromatograph at 260 degrees C for 1 min (HP 5890, DB-17 30 m x 0.25 mm I.D., 0.25 micron capillary; 0.7 ml/min nitrogen; nitrogen-phosphorus selective detection). The recovery was found to be very low from plasma (0.3% to 0.8%) but considerably higher from water (about 15%). Therefore, the high protein binding of antidepressants appears to be the main limiting mechanism for a better extraction. However, the analytes were well separated and the calibrations were linear between 125 ng/ml and 2000 ng/ml. The limits of quantification were about 90 ng/ml for imipramine and desipramine, 125 ng/ml for amitriptyline, trimipramine, doxepine, nortriptyline and mianserine and about 200 ng/ml for maprotiline, clomipramine and desmethylclomipramine. The recovery was improved by increasing the extraction time. The influence of the concentrations of the sum of proteins and of alpha-acid glycoprotein on the peak-area ratios ATAD/A I.S. and on absolute peak areas was studied. Peak-area ratios increased with decreasing protein concentration but were found to be independent on alpha-acid glycoprotein. A simple model for the explanation of the effect is presented. Measures for the improvement of sensitivity are discussed. As presented in this paper, which first describes SPME for the analysis of drugs in plasma, SPME with a short extraction time can be of only very limited value for therapeutic drug monitoring. Lower concentrations than the limit of quantification are usually found at therapeutic doses. The method can be useful for toxicological analysis after the accidental or suicidal intake of higher doses. However, an about 10-fold improvement of the sensitivity of the method seems to be possible.

Antidepressive Agents↗

PubMed1997

[Intercorrelation of psychopathological, morphologic, neurophysiologic an psychometric parameters in schizophrenic patients].

The present study was designed to determine the intercorrelation between schizophrenic symptoms, brain morphology, electrophysiological and neuropsychological variables. 44 patients, who met ICD-10 criteria for schizophrenic disorder, were included. At baseline, after 3 and 6 weeks BPRS, CGI, psychometric measurements and QEEG/ERP were performed. A CT scan was performed only at the beginning of the study. Data were evaluated by a multivariate test for data with an inherent structure. One of the most interesting findings is a correlation between BPRS total score and theta EEG power at baseline as well as under treatment. In conclusion, the study suggests the usefulness of multimethodological approaches in order to optimise diagnostic procedures in schizophrenia.

Adult↗

PubMed1997

The long-term effects of functional communication training in home settings.

A four-phase study was conducted in the homes of 4 young children who displayed aberrant behavior. Phases 1 and 2 consisted of a series of descriptive and experimental analyses to identify the environmental antecedents and consequences that controlled aberrant behavior. Phases 3 and 4 evaluated the short- and long-term effects of treatment on aberrant behavior, target mands, and collateral (social and toy play) behaviors. The effects of treatment were monitored for up to 27 months to assess long-term suppression of aberrant behavior. The assessment results successfully identified environmental events that occasioned and maintained aberrant behavior for all children. The short-term treatment resulted in immediate decreases in aberrant behavior for 3 of 4 children. Long-term treatment was successful for all children and was correlated with substantial response generalization. These results are interpreted in relation to functional equivalence, pivotal responding, and response generalization.

Behavior Therapy↗

PubMed1997

[Keratometry in dogs: two automatic hand-held keratometers compared].

In human medicine keratometric examinations are an essential tool for the determination of ocular refraction preceeding cataract operations. In dogs the use of manual keratometric methods is not feasible due to the lack of active cooperation. It is therefore necessary to apply autokeratometers which are also utilized in human pediatric patients. In this investigations we compared two portable automated keratometers in respect to their applicability in dogs. 40 dogs, comprising eight clinic beagles and 32 patient-dogs of various breeds were examined awake and under anesthesia using both hand-held keratometers. The horizontal and vertical corneal radius was measured consecutively by one investigator in all dogs and assessed statistically (standard deviation, analysis of regression and Student t-test). Both instruments yielded comparable results in all dogs. Furthermore, they were both tolerated well as they ensure a both rapid and minimal stress-inducing method of keratometry in dogs.

Anesthesia, General↗

PubMed1996

Simultaneous determination of amitriptyline, nortriptyline and four hydroxylated metabolites in serum by capillary gas-liquid chromatography with nitrogen-phosphorus-selective detection.

A method for the simultaneous quantification of the antidepressant drug amitriptyline, its demethylated metabolite nortriptyline and four hydroxy metabolites (E-10-hydroxyamitriptyline, Z-10-hydroxyamitriptyline, E-10-hydroxynortriptyline, Z-10-hydroxynortriptyline) in human serum or plasma has been developed. The method is based on a three-step liquid-liquid extraction followed by gas-liquid chromatography (split-splitless injection, HP-5, 25 m x 0.2 mm I.D., 0.33 microns capillary) with nitrogen-phosphorus-selective detection (GLC-NPD). The limits of detection are 1.5 ng/ml for amitriptyline, nortriptyline, E-10-hydroxyamitriptyline and Z-10-hydroxyamitriptyline and 3 ng/ml for E-10-hydroxynortiptyline and Z-10-hydroxynortriptyline. The within-day and between-day precision is between 6 and 15% at three concentrations (low, moderate and high) for amitriptyline, nortriptyline and E-10-hydroxy metabolites. At low concentrations of 10 ng/ml, the precision of the assay of the Z-10-hydroxy metabolites has been found to be up to 19%. Accuracy is between 91 and 115% for all analytes. The performance of the assay of the hydroxy metabolites is mainly determined by the cleanness and the deactivation of the quartz insert of the injector port. Therefore, every day a freshly cleaned and deactivated insert was used.

Amitriptyline↗

PubMed1996

A capillary gas-liquid chromatographic method for the assay of the neuroleptic drug zotepine in human serum or plasma.

A capillary gas-liquid chromatographic method suitable for the assay of the atypical neuroleptic drug zotepine in human serum or plasma was developed. A liquid-liquid extraction with three subsequent extraction steps was applied for sample preparation. The minimum detectable concentration was 1.0 ng ml-1. The within-day relative standard deviation (RSD) (n = 6) was 5.3% at 5 ng ml-1, 3.6% at 10 ng ml-1 and 6.1% at 100 ng ml-1. The day-to-day RSD (n = 6) was 9.3% at 10 ng ml-1 and 5.1% at 100 ng ml-1. Steady-state serum levels of four schizophrenic patients were measured.

Adult↗

PubMed1996

[Severe HELLP syndrome with temporary kidney and lung failure].

This report is on a severe case fo a HELLP-syndrome (H haemolysis, EL elevated liver enzymes, and LP low platelets). A 32-year old gravida developed severe preeclampsia with epigastric pain at 33 weeks' gestation. During a few hours post partum she showed disseminated intravascular coagulation (DIC) and required intensive care. The severe HELLP-syndrome was combined with a fast increasing acute respiratory distress syndrome (ARDS) and acute oligo-anuric renal failure. She was treated in the intensive-care unit for several days with artificial respiration, 10 acute haemodialyses, 4 plasma exchanges with fresh-frozen plasma and many blood and platelet transfusions. An early Caesarean section and treatment in the intensive care unit managed to turn the otherwise complicated progression of the disease. It is pointed out that plasma exchange with fresh-frozen plasma is a rarely employed treatment.

Acute Kidney Injury↗

PubMed1996

[Computer-assisted evaluation of a "medium resolution" HLA-DRB oligotyping of bone marrow donors].

One drawback of a 'medium resolution' generic dotblot oligonucleotide typing of the HLA-DRB locus has been the time consuming evaluation of the collected SSO-hybridisation datas. We developed a program on the basis of MS-ACCESS, written in visual basic, called HIDE (HLA Intelligent Data Evaluation) to manage this problem. HIDE offers a complete data management for the donor and the incoming sample, supports a membrane based data entry of the hybridisation-reactions and multiple testing of a sample. If an evaluation shows more than one matching allele combination, the result is summarized according to the main DRB-groups. The flexible structure of the program allows the entry of additional allelspecific reaction-patterns as well as the adaption to different SSO-typingsets.

Alleles↗

PubMed1996

[Prognostic value of Doppler flow measurement of the middle cerebral artery for morbidity of premature infants with null or negative flow in umbilical arteries].

We analysed 78 fetuses with absent or reverse endiastolic flow velocities (AREDFV) of the umbilical arteries with respect to fetal acidosis, resistance index of the middle cerebral artery (MCA) and abnormal neurological evaluations. A control group was matched for gestational age and normal umbilical artery flow velocity waveforms. Fetuses with AREDFV showed an increased incidence of fetal acidosis. The number of fetuses with abnormal neurological signs was significantly increased compared to the control group. Most of these fetuses (86%) showed abnormal blood flow velocity waveforms of the middle cerebral arteries called "brain-sparing effect". The combination of premature delivery in the 30th week of gestation, severe idiopathic respiratory distress syndrome, and a resistance index under the 10th percentile in the middle cerebral arteries seems to be a risk factor of the early neurological morbidity in fetus with AREDFV.

Blood Flow Velocity↗

PubMed1995

Sensitive gas-liquid chromatographic method for the assay of the neuroleptic drug cis(Z)-flupentixol in human serum or plasma.

A gas-liquid chromatographic (GLC) assay suitable for the analysis of the cis(Z)-stereoisomer of the antipsychotic drug flupentixol in human serum or plasma was developed. The minimal quantifiable concentration was 0.5 ng/ml and the day-to-day coefficient of variation was 11.2% at 1 ng/ml and 8.7% at 10 ng/ml. Following addition of perphenazine as the internal standard (I.S.) and aqueous NaOH, samples (2 ml) are extracted with n-hexane-isoamyl alcohol (98.5:1.5, v/v) (solvent), back-extracted to 0.1 M HCl and after one washing-step and addition of aqueous NaOH again extracted into 100 microliters solvent. After evaporation to dryness, the extract is reconstituted in 20 microliters solvent and evaporated to approximative 10 microliters. A 4-microliter aliquot is injected cool on-column onto the GLC system. A gas chromatograph HP 5890 with on-column injection port, nitrogen-phosphorus detector (NPD), a HP-1 25 m x 0.32 mm I.D., 0.52 micron capillary and hydrogen (3 ml/min, automated pressure control) as the carrier gas was applied. The negative influence of light on the assay was measured and discussed. The suitability of this method for clinical pharmacokinetic studies and therapeutic drug monitoring (TDM) was determined by the analysis of serum samples of 12 schizophrenic patients.

Adult↗

PubMed1995

Megabore capillary gas-liquid chromatographic method with nitrogen-phosphorus selective detection for the assay of haloperidol and reduced haloperidol in serum: results of therapeutic drug-monitoring during acute therapy of eight schizophrenics.

A gas chromatographic method using a HP-5 megabore capillary and nitrogen-phosphorus selective detection for the quantitative analysis of haloperidol (H) and reduced haloperidol (RH) in human serum or plasma is described. A 3-step liquid-liquid extraction is applied. The extraction yield of this procedure is 63% for haloperidol at 20 ng/ml. The limits of detection are 0.4 ng/ml for haloperidol and 1.0 ng/ml for the metabolite if 2 ml of body fluid are applied. At 10 ng/ml the within-day precision is 4.5% for H and 8.3% for RH. Serum levels of eight schizophrenic patients have been monitored weekly over a therapeutic period of six weeks. Seven patients mainly had metabolite ratios RH/H < 1 over the entire period of investigation. They exhibited a linear correlation between dose and serum concentration of haloperidol. In contrast, one patient had metabolite ratios RH/H > 1 over the entire period of the study. Due to considerable increased serum concentrations this patient did not show a linear correlation between the dose and the serum level of haloperidol.

Adult↗

PubMed1994

CK-BB as indicator of prenatal brain-cell injury in fetuses with absent or reverse end-diastolic flow velocities of the umbilical arteries.

The purpose of this study is to determine the levels of brain type isoenzyme of creatine kinase (CK-BB) as a possible indicator of a pre-existing intrauterine brain-cell damage in cord blood sera of fetuses with preceding absent or reverse end-diastolic flow velocities of the umbilical arteries (AREDFV). CK-BB isoenzyme activities were determined in umbilical cord sera of 13 newborn infants with preceding AREDFV and in 14 fetuses with low end-diastolic flow velocities (LEDFV) of the umbilical arteries. 50 newborn infants with elective cesarean section and normal umbilical artery blood flow velocity waveforms were used as controls. Two-tailed Student's t-test and Fischer's exact test were used for statistical evaluation of the results. CK-BB isoenzyme activity did not depend on gestational age. Fetuses with AREDFV showed a significant increase in CK-BB values, whereas fetuses with LEDFV had CK-BB activities within the normal range of the controls. The elevated CK-BB values of the AREDFV group were not correlated with fetal acidosis at birth. Brain-cell injury with leakage of CK-BB isoenzyme might be present in fetuses with AREDFV even before (preterm) delivery.

Blood Flow Velocity↗