D J Vonderschmitt

University of Zurich, Zürich, Zurich, Switzerland

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Publications (44)93.01 Total impact

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    ABSTRACT: We describe a normal-phase HPLC method for the stereospecific determination of R- and S-acenocoumarol and R- and S-phenprocoumon with S-warfarin as internal standard. The compounds were separated using a Whelk-O1 chiral stationary phase, detected by UV at 310 nm and quantified in the internal standard mode. Linearity was verified for acenocoumarol in the range of 15-2000 microg/l and for phenprocoumon from 15 to 2200 microg/l, respectively. The detection limits were 5 microg/l for all compounds. The recovery was >84% for R- and S-acenocoumarol and >74% for R- and S-phenprocoumon. The imprecision (C.V.) (50-1800 microg/l) for R- and S-acenocoumarol was <4.7% within-day and <7.8% between-day. For R- and S-phenprocoumon the respective values were <5.6% and <5.9%. The accuracy for all compounds was 96.5-110%.
    Journal of chromatography. B, Biomedical sciences and applications 06/2000; 742(1):131-42.
  • H R Schmid, D Schmitter, P Blum, M Miller, D Vonderschmitt
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    ABSTRACT: High resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a powerful research tool for the analytical separation of cellular proteins. The qualitative and quantitative pattern of polypeptides synthesized by a cell represents its phenotype and thus defines characteristics such as the morphology and the biological behavior of the cell. By analyzing and comparing the protein patterns of different cells it is possible to recognize the cell type and also to identify the most typical features of these cells. In applied pathology it is often difficult to identify the tissue of origin and the stage or grade of a neoplasia by cellular morphology analyzed by classical or immunostaining procedures. The protein pattern itself is the most characteristic feature of a cell and should therefore contribute to the identification of the cell type. For this reason we separated protein fractions originating from different lung tumor cell lines using 2-D PAGE and we compared the resulting patterns on a multivariate statistical level using correspondence analysis (CA) and ascendant hierarchical clustering (AHC). The results indicate that (i) protein patterns are highly typical for cells and that (ii) the comparison of the protein patterns of a set of interesting cell types allows the identification of potentially new marker proteins. 2-D PAGE is thus a unique and powerful tool for molecular cytology or histopathology, unveiling the protein expression level of tissues or cells.
    Electrophoresis 11/1995; 16(10):1961-8. · 3.26 Impact Factor
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    ABSTRACT: Nicotine consumption is one of the most important avoidable risk factors for atherosclerosis and cardiovascular, pulmonary as well as many other diseases. In daily practice one cannot always clearly detect whether a patient remains really abstinent. 68 patients following consultations for risk factors were included in this study. Smoking habits were evaluated by means of a questionnaire and by measurement of carbon monoxide concentration in the breath; also the cotinine concentrations in saliva and urine were investigated during consultation. Cotinine is one of the most important metabolic product of nicotine. Smokers showed significantly increased carbon monoxide concentrations in the breath as well as increased cotinine concentrations in urine and saliva. Anamnestic information from patients about their nicotine consumption correlated well with the cotinine concentration in urine and saliva (r = 0.54). The best correlation was found between creatine-corrected cotinine concentration and cigarette consumption on the day preceding in measurement (p < 0.001, r = 0.66). It is not clear if and to what extent cotinine determination may qualify for the evaluation of passive smoking; however, measurement of cotinine concentrations in saliva (or urine) represents a good biochemical parameter for the control of nicotine abstinence.
    Praxis 08/1995; 84(29-30):821-5.
  • D J Vonderschmitt
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    ABSTRACT: Numerical values for laboratory tests ae usually divided into positive and negative results by a discriminating value. This raises the question of the reliability of the results, i.e. the probability of the presence of the tested disorder, if the result is positive. The present paper shows that this probability depends on the sensitivity and the specificity of the test as well as on the prevalence of the disorder in the population of patients under investigation. The usual reference values for laboratory tests turns out to be highly specific. The predictive value of a test result can be considerably improved by limiting the diagnostic possibilities. Tests with insufficient sensitivity and specificity are not applicable in screening for disorders or diseases.
    Therapeutische Umschau 06/1995; 52(5):306-10.
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    ABSTRACT: A sensitive and precise gas chromatography-mass spectrometry method with selected ion monitoring has been developed for identification and quantification of the phencyclidine derivative ketamine in human plasma. The assay is based on an alkaline extraction from aqueous to organic solvent from plasma and an efficient gas chromatographic separation on a DB-5 capillary column. The analytical procedure has a coefficient of variation of 0.7-6.2% and from 1.3 to 8.7% within-day and from day-to-day analysis, respectively. The low level of sensitivity was 10 ng/ml. It was used to measure low plasma concentrations in volunteers during ketamine-induced experimental psychosis. The method is not enantio selective.
    Therapeutic Drug Monitoring 03/1995; 17(1):95-100. · 2.23 Impact Factor
  • M R Büeler, F Wiederkehr, D J Vonderschmitt
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    ABSTRACT: Urinary proteins from both sexes were analyzed by high resolution two-dimensional gel electrophoresis (2-DE). For well reproducible 2-DE patterns, the samples were concentrated and desalted in one step by vacuum dialysis. A reference map for urine proteins was established by the analysis of urine from 10 healthy persons. Proteins in urine that share immunogenicity with serum proteins were identified by use of antibody to whole human-serum protein in an affinity-column fractionation of urine and differential analysis of the adsorbed (serum component) and unadsorbed (non-serum component) fractions. For identification of individual proteins, coelectrophoresis, immunoblotting and affinity chromatography with corresponding antibodies were used. Proteins identified in the map, besides known serum proteins, included: the subunit of Tamm-Horsefall protein, the secretory component of IgA, constant breakdown products of alpha 1-antitrypsin and retinol-binding protein, the five isoforms of the beta chain of human chorionic gonadotropin and the subunit of prostatic acid phosphatase. In addition, we could demonstrate three proteins which are markedly pronounced in female urine, especially pregnant women. To get more information about the native properties of various urinary proteins, they were separated into four main peaks according to their sizes using fast protein liquid chromatography equipment. Possible interpolypeptide disulfide bonds were studied using a nonreducing 2-DE system. 2-DE in combination with other methods seems to be a valuable tool for the characterization of urinary proteins in defined renal or extra-renal diseases. An example is given by analyzing the immune complexes from seven patients with a urinary tract infection.
    Electrophoresis 02/1995; 16(1):124-34. · 3.26 Impact Factor
  • N Feng, B Schnyder, D J Vonderschmitt, B Ryffel, R A Lutz
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    ABSTRACT: The interleukin-13 receptor is characterized by ligand-binding and crosslinking studies and compared with the interleukin-4 receptor. Crosslinking of radio-labeled hIL-4 and hIL-13 to the receptors on human carcinoma and mast cell lines demonstrated a predominant subunit at 130 kDa with two other minor bands of lower molecular mass (75 kDa and 65 kDa) in autoradiography. All binding of 125I-IL-13 was specifically blocked when the carcinoma cell suspensions were incubated with an excess of unlabeled hIL-4. However, unlabeled hIL-13 was unable to completely displace 125I-hIL-4 from the 130 kDa protein. In addition, 125I-hIL-13 showed no binding to mouse fibroblast cells transfected with human 130 kDa hIL-4 receptor c-DNA. Using weighted nonlinear computer modeling of the data from several equilibrium binding studies with human mast cells, a model of two binding sites for IL-4 (Kd = 50 and 190 pmol/L) and one site for IL-13 (Kd = 100 pmol/L) fitted better than a one site model with a very high level of significance (F = 10.66, P < 0.0001). It can be concluded that human IL-4R and hIL-13R are similar but distinct. This conclusion is supported here for the first time by a strong statistical criterion.
    Journal of Receptor and Signal Transduction Research 01/1995; 15(7-8):931-49. · 1.63 Impact Factor
  • H R Ha, K M Rentsch, J Kneer, D J Vonderschmitt
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    ABSTRACT: We describe a new high-performance liquid chromatography (HPLC) method for measurement of midazolam and its major metabolite, alpha-hydroxymidazolam, in clinical samples. Plasma or urine was mixed with 100 ng internal standard Ro 05-6669 and borate buffer, 0.1 M, pH 9. Midazolam and its related compounds were extracted into diethylether. The organic phase was evaporated to dryness. The residue was dissolved in HPLC mobile phase [methanol-isopropyl alcohol-perchloric acid, 0.5 microM (57:25:18)] and injected into the chromatograph. The separation of substances was performed on an Spherisorb S5CN 250 x 4.6 mm HPLC column maintained at 45 degrees C. The detection was performed by absorption measurement at 245 nm. At a flow rate of 1.7 ml/min, the retention times of Ro 05-6669, 1,4 dihydroxymidazolam, alpha-hydroxymidazolam, 4-hydroxymidazolam and midazolam were 4.0, 6.7, 7.8, 9.6, and 10.8 min, respectively. In the concentration range of 5-1,000 ng/ml, the calibration graphs for both compounds were linear. The coefficients of variation of the between-day and within-day assay were < 14% for the concentration range 5-10 and < 7% for the range 10-600 ng/ml. The limits of detection for midazolam and alpha-hydroxymidazolam were 2 and 4 ng/ml, respectively. This assay is more sensitive than earlier methods; it is simple and rapid, and it enables the quantification of midazolam and its alpha-hydroxy metabolite with very good precision and accuracy in human plasma and urine.
    Therapeutic Drug Monitoring 09/1993; 15(4):338-43. · 2.23 Impact Factor
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    K Gautschi, B Keller, H Keller, P Pei, D J Vonderschmitt
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    ABSTRACT: The relationship between the concentration of the analyte and the imprecision of an analytical method can be displayed by the precision profile in which the coefficient of variation (relative standard deviation) is plotted against the concentration of the analyte. The function of the curve of the profile and its confidence limits can easily be assessed by a computer program developed by W.A. Sadler & M.H. Smith (Clin. Chem. 36 (1990), 1346-1350). For the assessment of limits of detection and of quantification the following procedure is proposed: The lower (and upper) limit of the measuring interval is defined by the point at which an acceptable CV-line intersects the confidence limit. If, in the variance function one sets the concentration to zero, the normal distribution of the random errors of the blank will result. The mean of the next adjacent normal distribution, following the variance formula and overlapping the "zero-distribution" by a defined amount, represents the limit of detection. Within the described measuring interval, or within a fraction of it, one might construct overlapping normal distributions in an analogous manner. Their number represents the "power of definition" (PD) (instead of the "analytical sensitivity"), which also depends on the concentration of the determinand according to the variance function. We tested these hypotheses by a comparison of two methods for the determination of cyclosporin A (ciclosporin, INN). Our results demonstrate that the data of the lower limits of the measuring interval and of the limit of detection agree well with data from the literature obtained in extensive interlaboratory surveys.
    European journal of clinical chemistry and clinical biochemistry: journal of the Forum of European Clinical Chemistry Societies 07/1993; 31(7):433-40.
  • F Wiederkehr, M R Büeler, R Fried, D J Vonderschmitt
    Schweizer Archiv für Neurologie und Psychiatrie (Zurich, Switzerland: 1985) 02/1993; 144(3):210-2.
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    K. Gautschi, B. Keller, H. Keller, P. Pei, D. J. Vonderschmitt
    Clinical Chemistry and Laboratory Medicine - CLIN CHEM LAB MED. 01/1993; 31(7):433-440.
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    ABSTRACT: Analytical performance and practicability of the new Boehringer Mannheim/Hitachi 747 analysis system were assessed in a multicentre evaluation involving four laboratories. The analytical performance was evaluated according to a protocol similar to the ECCLS guidelines and comprised 13 analytes including enzymes, substrates and electrolytes. About 65,000 results were obtained within three months. The evaluation was planned and supported by a program system called "Computer Aided Evaluation". Acceptance criteria have been established for judging the results. The median of the within-run coefficients of variation (CVs) in control sera of all methods was below 1%, being far below the acceptance limit of 2%. The median of CVs of between-days imprecision was below 2% (acceptance criterion 3%). The high degree of precision prompted us to set up a biometrical model suitable for the differentiation between deviant points, outliers and measurements that can still be explained by the system performance. No relevant drift effects were observed during eight hours. The methods were linear over a wide range, avoiding rerun analysis in most cases. No sample-related carry-over was found. Reagent-dependent carry-over outside the acceptance limits was measured from uric acid to phosphorus to a slight extent, and from triacylglycerols to lipase, as well as from total protein to bilirubin to a perceptible degree. It can be avoided by separating these reagent combinations in the channel arrangement. Taking a systematic deviation of more than 10% as unacceptable, four of the 13 analytes suffered from interference by haemoglobin, one by bilirubin and one by turbidity. The Boehringer Mannheim/Hitachi 747 analysis system is capable of determining serum indices which in combination with the interferogram allow an assessment of the interference. With the exception of chloride the recovery of the assigned values for all control sera showed values between 95 and 105%. Out of 40 method comparison studies for enzymes and substrates, 31 yielded regression equations with less than 5% proportional errors and less than 5% constant errors. Deviations exceeding these acceptance criteria can be explained by differences in the reagent formulation, in the method employed or in calibration. The agreement of the ISE method comparisons was within a +/- 5% deviation over a wide analytical range. Practicability of the Boehringer Mannheim/Hitachi 747 analysis system was assessed with the help of a questionnaire, in which properties of the instrument were quantified, thus permitting a relatively objective rating. The 190 questions were placed in 14 groups, each dealing with an attribute of the instrument.(ABSTRACT TRUNCATED AT 400 WORDS)
    European journal of clinical chemistry and clinical biochemistry: journal of the Forum of European Clinical Chemistry Societies 01/1993; 30(12):881-99.
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    E I Minder, J P Vuilleumier, D J Vonderschmitt
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    ABSTRACT: Unpleasant specimens, sensitive analytes, and a lengthy chromatographic procedure were the main reasons we implemented fecal porphyrin analysis with a laboratory robot. We describe the system in detail and compare it with the same technique performed manually. The day-to-day variation of assays of standards was lower with the robot than with the manual operation: 8% (CV) for coproporphyrin I and 11% for protoporphyrin IX. We repeatedly analyzed a specimen from a healthy volunteer and determined that the specimen contained (in nmol/g dry wt) 7.1 (SD 0.7) for coproporphyrin I, 3.0 (SD 0.4) for coproporphyrin III, and 44.4 (SD 4.3) for protoporphyrin IX. Upper reference limits as measured in 20 healthy volunteers were 20 nmol/g dry wt for coproporphyrin I, 12 nmol/g for coproporphyrin III, and 80 nmol/g for protoporphyrin IX. We also present characteristic chromatograms for samples from various different porphyrias that exhibit abnormal fecal porphyrin excretion. Calculations of return on investment show that the robot, working at full capacity, is a profitable tool.
    Clinical Chemistry 05/1992; 38(4):516-21. · 7.15 Impact Factor
  • N Feng, E I Minder, T Grampp, D J Vonderschmitt
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    ABSTRACT: A highly sensitive and simple gas chromatographic-mass spectrometric method is described for the identification and quantification of ergotamine in plasma or serum. Ergotamine is extracted with chloroform from the alkalinized sample and detected by electron ionization mass spectrometry. This analytical method was selected for an intense high-mass ion ideal for the specific quantification. It shows good linearity in the range from 50 pg/ml to 50 ng/ml for ergotamine in plasma. The practicability of this method is demonstrated by determining the plasma concentration of ergotamine in a sample from a patient.
    Journal of Chromatography A 04/1992; 575(2):289-94. · 4.61 Impact Factor
  • R Fried, F Wiederkehr, D J Vonderschmitt
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    ABSTRACT: A method is described for the characterization of protein antigens from circulating immune complexes from plasma. Free immunoglobulins G were separated from larger immune complexes by gel filtration with a fast protein liquid chromatographic system. The collected immune complexes were dissociated with 4M urea into antigens and antibodies. With a second column run with 4M urea, antigens smaller than 120 kDa were separated from unloaded antibody fractions. After concentration, they were analyzed by two-dimensional gel electrophoresis.
    Electrophoresis 01/1992; 13(9-10):718-9. · 3.26 Impact Factor
  • D J Vonderschmitt
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    ABSTRACT: New techniques for stat-tests (e.g. "dry chemistry") are discussed with respect to their reliability, speed and economy. Based on these factors, a list of stat-tests is proposed which appears to meet the needs of the general practitioner's laboratory. The new techniques may also affect hospitals and pharmacies.
    Schweizerische medizinische Wochenschrift 01/1992; 121(50):1870-5. · 1.68 Impact Factor
  • P Pei, C Cigler, D J Vonderschmitt
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    ABSTRACT: In the hospital clinical laboratory, plasma potassium and sodium are usually determined by using a flame photometer or ion-selective electrodes, for which special equipment is required. The new enzymatic methods of sodium and potassium can be used as a routine chemical method. We evaluated the new enzymatic methods for the determination of sodium and potassium in human plasma on the Hitachi 747. The sodium and potassium assay kits were purchased from Boehringer Mannheim, Germany. Precision studies were performed using three levels of pool plasma. The coefficients of variation (CV) of sodium and potassium determination were less than 1.0% and less than 2.2% by intraassay and interassay respectively. The recoveries of the assigned values of the ten control sera were 97-102%. Comparisons with results either from flame photometry and from ion-selective electrodes showed no clinically relevant differences for 100 patient samples. Performance of the enzymatic methods for Na+ and K+ is clinically comparable to flame photometry or ion-selective electrodes in the routine clinical chemistry laboratory.
    Schweizerische medizinische Wochenschrift 01/1992; 121(50):1883-6. · 1.68 Impact Factor
  • E.I. Minder, D.J. Vonderschmitt
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    ABSTRACT: Unpleasant specimens, sensitive analytes and a lengthy chromatographic procedure were the main reasons to implement the analysis of fecal porphyrin using a laboratory robot. It was considered as a pilot project for the clinical laboratory to examine if manual methods for such unpleasant, low-volume work can be replaced by flexible automation. The system consists of a Zymate II core system with a number of peripherals required for liquid-liquid extraction, a reversed-phase high-performance liquid chromatographic system with fluorescence detection and a personal computer as system controller. Programming was performed in EASYLAB language for robot control and in HP Basic version 5.1 for data reduction. The reproducibility (C.V. = 10%) is better than for the manual technique and the system has been used routinely for two years. 250 samples have been analysed. The flexibility of the robot enabled other methods to be implemented on the same system. Thus, determination of urosynthase activity (150 samples per year) and porphyrines in urine (650 samples in two years) are run partially automated. These three analyses save US$ 50 000 per year, compared to an investment of US$ 55 000. As the number of analyses is rapidly increasing, the robot will soon be a profitable investment.
    Chemometrics and Intelligent Laboratory Systems. 01/1992;
  • F Wiederkehr, M R Büeler, D J Vonderschmitt
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    ABSTRACT: The protein nature of soluble immune complexes from fresh plasma was studied by combining several analytical biochemical techniques. Free immunoglobulins (Ig) G were separated from larger immune complexes by gel permeation chromatography. In a second step, immune complexes, free IgA and IgM were isolated by protein-A and protein-G affinity chromatography and analysed by two-dimensional gel electrophoresis. Sixteen plasma samples from healthy donors were analysed and evaluated visually. Their protein profiles on the gels turned out to be similar, showing only slight quantitative differences. In one case, additional proteins were detected. To prove the ability of the method, immune complexes were analysed from four plasma samples that showed macro creatine kinase type 1, a complex formation between creatine kinase BB and IgG. This methodology can be used for the examination of immune complexes of unknown protein composition in serum or plasma.
    Journal of Chromatography A 06/1991; 566(1):77-87. · 4.61 Impact Factor
  • D J Vonderschmitt
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    ABSTRACT: Principle and function of systems that work with carrier-bound reagents are explained for the practitioner, in order to give a better overview over the possibilities and limitations of 'dry chemistry'. The four systems that are currently available for the doctor's office are presented and compared. The many possibilities for failures and ways to avoid them are shown. Finally, the obligation for a quality assessment scheme is recalled and a reasonable use of 'dry chemistry' panels discussed.
    Schweizerische Rundschau fur Medizin Praxis = Revue suisse de medecine Praxis 04/1991; 80(13):335-9.