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W D Lehmann

Publications and source records attributed to W D Lehmann.

At least 73 records · Page 4Linked to original sources
PubMed1985

Investigations on antipyrine metabolism V. Differentiation of two isomeric hydroxyantipyrine glucuronides by field desorption and fast atom bombardment mass spectrometry.

The glucuronide conjugates of the two isomeric antipyrine phase I metabolites of antipyrine in man, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine have been analysed by field desorption and fast atom bombardment mass spectrometry. These isomers could be clearly distinguished on the basis of their fragmentation behaviour which was found to correlate with that observed under pyrolysis electron impact conditions.

Antipyrine↗
PubMed1984

Detection of heterozygous carriers for phenylketonuria by a L-[2H5]phenylalanine stable isotope loading test.

Oral loading with 25 mg/kg of pentadeuterated L-phenylalanine has been used for the discrimination between normozygous subjects and carriers for phenylketonuria. The test provides five types of data derived from plasma Phe and Tyr concentrations on which the discrimination can be based: fasting phenylalanine/tyrosine ratios, total Phe levels, total Phe/total Tyr ratios, absolute L-[2H5]phenylalanine plasma levels, and L-[2H5]Phe/L-[2H4]Tyr ratios. Absolute L-[2H4]Tyr and total L-Tyr concentrations provide the poorest discrimination with statistical classification errors around 30%. The corresponding classification error of fasting Phe/fasting Tyr ratios was circa 13%, and both labelled Phe/labelled Tyr and total Phe/total Tyr concentration ratios gave minimal errors below 2%.

Deuterium↗
PubMed1983

Stereospecificity of phenylalanine plasma kinetics and hydroxylation in man following oral application of a stable isotope-labelled pseudo-racemic mixture of L- and D-phenylalanine.

L-[15N]Phenylalanine and D-[2H5]phenylalanine have been administered orally to two healthy adult volunteers as a pseudo-racemic mixture at a dose of 25 mg/kg each. After oral application, the plasma kinetics of phenylalanine and tyrosine have been followed by the combined use of high pressure liquid chromatography and field desorption mass spectrometry. Additional incubation with D-amino acid oxidase was used to determine the enantiomeric composition of the differently labelled species of phenylalanine and tyrosine. D-Phenylalanine plasma levels show a faster rise to higher maximum values compared to L-phenylalanine (D/L ratio at maximum 3.19, 3.26). L-Phenylalanine is efficiently hydroxylated to L-tyrosine. In contrast, conversion of D-phenylalanine to the L-form with subsequent hydroxylation to L-tyrosine was observed. From the plasma kinetics it is estimated that about 1/3 of the applied dose of 25 mg/kg of D-phenylalanine is converted to the L-isomer. Of the administered dose of L-phenylalanine only very small amounts are excreted into urine as such (0.25%, 0.8%), whereas a substantial amount of the D-phenylalanine dose is found in urine (27.4%, 38.0%).

Adult↗
PubMed1983

Characterization and quantification of human plasma lipids from crude lipid extracts by field desorption mass spectrometry.

The main classes of human plasma lipids, free fatty acids, cholesterol, cholesterol esters, triglycerides and phosphatidylcholines were identified and quantified from samples of human plasma by field desorption mass spectrometry. A crude lipid extract was prepared from 50 microliters of human plasma and a 1-5% aliquot thereof was subjected directly to field desorption mass spectrometry without any chromatographic separation of the extract constituents. Within the classes of free fatty acids, triglycerides and phosphatidylcholines the fatty acid profile was obtained directly from the mass spectrum and accurate quantification could be achieved by the addition of stable isotope labelled internal standards.

Cholesterol↗
PubMed1983

Fatty acid profiling of phospholipids by field desorption and fast atom bombardment mass spectrometry.

Natural phosphatidylcholines, phosphatidylethanolamines and sphingomyelins have been investigated by field desorption and fast atom bombardment mass spectrometry. It is demonstrated that using these soft mass spectrometric ionization techniques, accurate, fast, and sensitive fatty acid profiling of phospholipids can be performed. With respect to the analysis of intact molecular species both ionization techniques reveal similar results. Using field desorption, a specific fragment ion provides a fast access to the total distribution of fatty acids in complex lipids. Generally, a good agreement between the mass spectrometric abundance data and those produced by gas chromatographic analysis is observed.

Animals↗
PubMed1982

Investigations on antipyrine metabolism. II--Analysis of conjugated metabolites of antipyrine in rat and human urine by off-line combination of liquid chromatography and field desorption mass spectrometry.

The complex pattern of conjugates in the metabolism of antipyrine in man and rat has been investigated using an off-line combination of liquid chromatography and field desorption mass spectrometry. Using this approach, field desorption mass spectrometry enables the direct identification of underivatized glucuronides and sulphates in antipyrine metabolism on the basis of the corresponding protonated or cationized molecules representing the base peaks in the field desorption mass spectra. All conjugated metabolites of antipyrine established so far--four glucuronides and three sulphates--were identified in extracts of urine after stepwise purification by column chromatography and subsequent mass spectrometric analysis.

Adult↗
PubMed1982

Preparative isolation and purification of urinary conjugates in antipyrine metabolism in man and rat.

A series of six major urinary conjugates in the metabolism of antipyrine in man and rat has been investigated. A preparative isolation procedure has been developed using chromatography of methanolic extracts from urine on silica gel. In a two-step chromatographic procedure, methanolic extracts are first separated in 1) a "free fraction", containing unconjugated phase-I-metabolites and unchanged antipyrine, 2) a sulfate fraction and 3) a glucuronide fraction. Sulfate and glucuronide fraction, respectively, are each subjected to a second run for separation into their three components. Thus, the following conjugates have been prepared: 4-hydroxy-antipyrine sulfate, norantipyrine sulfate, 4,4'-dihydroxy-antipyrine sulfate, and 4-hydroxy-antipyrine glucuronide, norantipyrine glucuronide, 3-hydroxymethyl-antipyrine glucuronide. Methodology is also applicable to bile fluid and liver perfusate. Stability of isolated conjugates against acid hydrolysis has been studied to show that strongly marked differences exist in this series of conjugates. Field desorption mass spectrometry has been used for the direct identification of intact conjugates in an underivatized form. Using 13C-NMR, the structure of norantipyrine glucuronide has been established as an 5-enol glucuronide. By analogy, a structure of 5-enol sulfate is proposed for norantipyrine sulfate. From a semiquantitative examination by TLC of urine extracts from man and rat, it becomes apparent, that in the rat, at the dose level studied, sulfate formation is the predominant conjugation pathway. In man, glucuronides are the most prominent type of conjugates. Formation of sulfates is minimal up to a dose of 15 mg/kg antipyrine.

Adult↗
PubMed1982

Accurate quantification of nonesterified and total cholesterol in plasma and urine from crude lipid extracts by stable isotope dilution and field desorption mass spectrometry.

Levels of free and total cholesterol were quantified in control sera and human urine using [2H7]cholesterol or [13C2]cholesterol as internal standard and field desorption mass spectrometry for the quantification. These analyses are performed using a crude chloroform extract without chromatographic separation of the constituents. Due to the extremely soft ionization conditions in field desorption, the constituents of the crude lipid extract predominantly form molecular ion species and only a very low amount of fragment ions of low relative abundance thus minimizing the possibility of ion overlap in the mass spectrum. Mass spectrometric quantification of cholesterol in two control sera resulted in data within the range of assigned concentrations. The standard deviations of the mass spectrometric data were around +/- 2%. Generally, 50 microliters of serum or plasma or 500 microliters of urine are extracted and the mass spectrometric quantification performed using an aliquot of 2-10%. A characteristic pattern of intact cholesteryl esters is also obtained.

Body Fluids↗
PubMed1981

Assay for plasma free phenylalanine and tyrosine by high-pressure liquid chromatography and field desorption mass spectrometry and its application to an in vivo study of the phenylalanine hydroxylating system in man.

An analytical assay for the determination of free amino acids in human plasma based on high-pressure liquid chromatography and field desorption mass spectrometry has been developed. Compared with assays using gas chromatography and mass spectrometry, this method appears to be advantageous with respect to the analysis of polar and/or labile amino acids. Using stable isotope labelled analogues as internal standards quantifications by field desorption can be performed on about 250 pmol of individual amino acids as dansyl derivatives, corresponding to about 10 mul of human plasma. The practicability of the assay is demonstrated by a stable isotope in vivo study of the phenylalanine hydroxylating system in man.

Chromatography, High Pressure Liquid↗
PubMed1980

[Caesarean section with splenectomy in a patient with idiopathic thrombocytopenic purpura (author's transl)].

We report a patient who had a marked exacerbation of idiopathic thrombocytopenic purpura at 33 weeks of pregnancy. The platelet count rose in response to treatment with high doses of glucocorticoids and it was possible to allow the pregnancy to continue until 39 weeks. The patient was then delivered by elective Caesarean section and she had a splenectomy at the same time. A transfusion of platelets was administered as soon as the splenic vessels had been clamped. The resultant excess of platelets necessitated treatment with acetylsalicylic acid. At 18 months after Caesarean section and splenectomy the thrombocytopenia had not recurred. The infant had transient neonatal thrombocytopenia but required no active treatment for this.

Adult↗
PubMed1980

Fibroelastosis of the right ventricle in two brothers of triplets.

We present an autopsy report of endocardial fibroelastosis of the right heart in two brothers of triplets. Beside this anomaly no other macroscopical malformations in the hearts were found. Morphologically an unusual hypertrophy of the subendocardial myocardiocytes in the right heart was observed. A history of tocolysis (sympathomimetic drugs for treatment of premature labour) was the main reason for publishing this case report. We could not answer the question if the drug was causative or only coincident with the observed lesions.

Autopsy↗
PubMed1978

[Favorable effects of estrogens and progesterones on general diseases].

Estrogens and progestagens exert positive effects on some general diseases as iron deficiency, anemia, premenstrual syndrome, intermenstrual migraine, akne, seborrhoea, hirsutism, androgenetic alopecia, slerodermia, rheumatoid arthritis, osteoporosis and depressive disorders. The mechanism of action and the mode of treatment in such cases are discussed.

Acne Vulgaris↗
PubMed1978

[Clinical and biochemical studies in three pregnancies with placental sulphatase deficiency (author's transl)].

Three pregnancies (two I. parae and one II. para) with abnormally low urinary estrogen excretion of less than 5 mg estrogens per day have been investigated in this study. After intravenous injection of 100 mg DHA-S to the mothers no increase of estrogen production was observed. The level of human placental lactogen, was found within normal range. Ultrasonographic measurement of fetal size and monitoring of the fetal heart rate have demonstrated fetal benefit. At the end of pregnancy the cervix of both did not dilate after infusion of Syntocinon. Healthy male infants were delivered by Caesarean sections in both cases. The II. para, however, developed spontaneous labour and delivery at term. Clinical and laboratory tests have indicated the possibility of rare placental sulphatase deficiency. After delivery the placental steroid sulphatase activity was measured as the rate of hydrolysis of (6,7-3H) oestrone-sulphate or (4-14C) dehydroepiandrosterone-sulphate during in vitro incubation with the homogenate or the microsomal fraction from the pathological placentae. In all three cases the specific activity of 3-sulphatase was considerably (more than 80%) decreased when compared to three normal placentas, whereas the activity of the other enzymes (17beta-hydroxysteroidoxidoreductase, delta4/5-isomerase, aromatizing enzyme system) was found within the normal range.

Adult↗
PubMed1978

Quantitative field desorption mass spectrometry. V. Discussion of methodology and examples of applications.

The possibilities for the application of field desorption mass spectrometry in quantitative analyses are described and evaluated. The advantages of and the sources of errors in the use of different standards as well as in the application of different methods such as photographic detection, single ion monitoring, repetitive scanning, selected ion monitoring, and double ion detection are illustrated by representative examples. Sensitivity and precision of the different techniques are evaluated. Most importantly, the use of stable isotope labelled compounds as internal standards has enabled quantitative determination with good precision, accuracy, and sensitivity. In order to demonstrate the capabilities of the methods, examples of applications are presented and the scope of quantitative analysis with field desorption mass spectrometry is discussed.

Humans↗
PubMed1978

Determination of lithium in microlitre amounts of human body fluids at therapeutic and normal levels by stable isotope dilution and field desorption mass spectrometry.

The use of field desorption mass spectrometry for the determination of lithium in body fluids at therapeutic levels--ppm region--as well as at the normal level--ppb region--has been developed. The use of a stable isotope enriched internal standard, together with the outstanding sensitivity of field desorption for alkali cations and the high specificity of mass spectrometry, allows a quantitative determination of lithium in microlitre amounts of body fluids, such as plasma, saliva and urine. The assay allows a determination of lithium even at ultratrace concentrations where routine spectroscopic procedures cannot be applied. Analysis of plasma required a simple protein precipitation, whereas saliva and urine could be analysed without treatment. The precision of the data obtained ranged from 2--10%. The time consumption for one analysis in routine work is about 20--30 min.

Humans↗
PubMed1978

Determination of choline and acetylcholine in distinct rat brain regions by stable isotope dilution and field desorption mass spectrometry.

The determination of choline and acetylcholine by field desorption mass spectrometry from rat brain tissue samples has been demonstrated. Essential points of the assay are the use of stable isotope labelled internal standards, a simple ion pair extraction procedure, direct analysis of the quaternary ammonium ions without derivatization, and accumulation of the electrically recorded field desorption ion signals with a multi-channel analyser. The analysis of sample amounts in the picogram range gave quantitative data of good precision (0.6--10% standard deviation).

Acetylcholine↗
PubMed1978

[Progress in diagnosis and treatment of pregnancies with low birthweight infants (author's transl)].

In order to prove the progress in diagnosis and treatment of pregnancies with low birthweight we performed a retrospective computer-analysis of three groups of patients including newborns below 2750 g delivered dumping the last 10 years. The first group contains the years 1967/68; the deliveries of low birthweight infants were monitored without cardiotocogram. The second group of patients from the years 1971/72 was monitored continuously during delivery by cardiotocogram. The endocrinologic diagnostic methods for detection of a possible placental insufficiency in low weight fetus were applied regularly (DHEA-S-loading test, oestriol, HPL). The treatment of premature newborns with respiratory distress syndrome was facilitated by CPAP. A thorough ultrasound diagnosis was available additionally for the third group of patients. Long term treatment with Partusisten was applied in cases of premature labour in this group and betamethasone-therapy was used for accelleration of fetal lung maturation. With a nearly constant number of preterm eutrophic newborns, preterm infants with retarded growth and mature infants with retarded growth over a period of ten years the unpurified mortality rate decreased from 14.3% to 6.7% when the pregnancies and deliveries had intensive (obstetrical medical) care. With the help of Shirodkar procedure and tocolytic treatment the birthweight could be shifted significantly into the favourable group over 2000 g. The prenatal prophylactical treatment of the respiratory distress syndrome with beta-methasone and the postnatal CPAP-therapy decrease the mortality rate caused by respiratory deficiency from 13.7% to 6.4%. The preventive caesarean section in cases of low birthweight infants with abnormal positions in utero helped to reduce the mortality rate from 21% to 10.6% in these cases. The accuracy of prenatal diagnosis of intrauterine retarded fetal growth by hormone analysis and ultrasonic measurement of the fetus was improved from 24% to 66%.

Female↗