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Biomedical subjects

H Maurer

Publications and source records attributed to H Maurer.

At least 73 records · Page 4Linked to original sources

Metabolism of trimipramine in man.

This paper describes studies on the metabolism of the tricyclic antidepressant 5-(3-dimethylamino-2-methylpropyl)-10,11-dihydro-5H-dibenz[b,f]azepine (trimipramine, Stangyl) in man. The metabolites were identified after cleavage of conjugates, extraction and derivatisation by acetylation in human urine using gas chromatography-mass spectrometry. Besides the unchanged trimipramine (T), the following 15 metabolites could be identified: mono- and dihydroxy-T, hydroxy-methoxy-T; iminodibenzyl (I), mono- and dihydroxy-I, hydroxy-methoxy-I; nor-T (NT), mono- and dihydroxy-NT, hydroxy-methoxy-NT; bis-nor-T (BNT), mono- and dihydroxy-BNT and hydroxy-methoxy-BNT. Therefore 3 overlapping metabolic pathways can be postulated: N-dealkylation of the nitrogen in the iminodibenzyl ring, 1- and 2-fold N-demethylation of the nitrogen in the side chain and 1- and 2-fold aromatic hydroxylation of the iminodibenzyl ring. The dihydroxy metabolites are partly methylated at one of the hydroxy groups. The hydroxy metabolites are conjugated additionally.

Biotransformation↗

Identification and differentiation of alkylamine antihistamines and their metabolites in urine by computerized gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric screening procedure is described for the identification and differentiation of the following alkylamine antihistamines and their metabolites in urine: azatadine, benzquinamide, brompheniramine, chlorphenamine, (clofedanol), cyproheptadine, dimetindene, ketotifen, mebhydroline, phenindamine, pheniramine, pyrrobutamine, terfenadine and tolpropamine. After acid hydrolysis of the conjugates, extraction and acetylation, the urine samples were analysed by computerized gas chromatography-mass spectrometry. Using ion chromatography with the selective ions m/z 58, 169, 203, 205, 230, 233, 262 and 337, the presence of alkylamine antihistamines and/or their metabolites was indicated. The identity of positive signals in the reconstructed ion chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (OV-101) are documented. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs.

Acetylation↗

Screening procedure for the detection of alkanolamine antihistamines and their metabolites in urine using computerized gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric screening procedure for the detection of the following alkanolamine antihistamines and their metabolites in urine after acid hydrolysis and acetylation is described: bencyclane, carbinoxamine, chlorbenzoxamine, chlorphenoxamine, clemastine, diphenhydramine, diphenylpyraline, doxylamine, mecloxamine, medrylamine, orphenadrine and phenyltoloxamine. The acetylated extract was analysed by computerized gas chromatography-mass spectrometry. An on-line computer allows rapid detection using ion chromatography with the ions m/z 58, 139, 165, 167, 179, 182, 218 and 260. The identity of positive signals in the reconstructed ion chromatograms was confirmed by a comparison of the stored full mass spectra with the reference spectra. Possible interferences with related compounds that yield the same hydrolysis products or metabolites are discussed. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (OV-101) are documented. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs.

Acetylation↗

Identification and quantification of ethylene glycol and diethylene glycol in plasma using gas chromatography-mass spectrometry.

A method for the gas chromatographic-mass spectrometric identification and quantification of ethylene glycol and diethylene glycol in plasma is described. Such a method is necessary in clinical and forensic toxicology to diagnose probable intoxication and to control the efficacy of detoxification. For sample preparation, the glycols were isolated using acetone after the addition of 1,3-propylene glycol as internal standard. The glycols were then esterified by pivalic acid (pivalic acid anhydride, triethylamine and methanol, 70 degrees C, 15 min) to improve their gas chromatographic characteristics. The glycols were first identified by a comparison of the full mass spectra with reference spectra and then quantified. Therefore, the peak area ratio in the total ion chromatogram (ethylene glycol or diethylene glycol/1,3-propanediol) of the sample was compared with the calibration curve in which the peak area ratios of the standards (0.05, 0.1, 0.5, 1 and 2 g/l), prepared in the same way, were plotted versus their concentrations. The method was linear at least from 0.05 to 2 g/l, with a detection limit of less than 0.01 g/l. The analytical recoveries were 99.2-102.9% for the different concentrations. Precision studies show coefficients of variation of 3.0-6.3% for the different concentrations.

Ethylene Glycols↗

Identification of phenothiazine antihistamines and their metabolites in urine.

Identification of the phenothiazine antihistamines alimemazine, dimetotiazine, isothipendyl, mequitazine, oxomemazine, promethazine, thiethylperazine, triflupromazine and their metabolites in urine is described. After acid hydrolysis of the conjugates, extraction and acetylation the urine samples were analysed by computerized gas chromatography-mass spectrometry. Using ion chromatography with the selective ions m/z 58, 72, 100, 114, 124, 128, 141, and 199 the possible presence of phenothiazine antihistamines and/or their metabolites was indicated. The identity of positive signals in the reconstructed ion chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (OV-101) are documented. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs.

Animals↗

Histopathology of childhood sarcomas, Intergroup Rhabdomyosarcoma Studies I and II: clinicopathologic correlation.

Histopathologic material from 1,782 patients registered in the Intergroup Rhabdomyosarcoma Study Committee (IRS)-I and -II were reviewed by the IRS Pathology Committee in order to provide a uniform approach to classification and correlate patient survival with tumor type. Categories considered eligible were the four types of rhabdomyosarcoma (RMS) (criteria of Horn and Enterline), extraosseous Ewing's tumor (EOE), and a group of somewhat variable undifferentiated sarcomas designated small round cell sarcoma, type indeterminate (STI). Tumors that were clearly sarcomas but were unclassifiable also were included (NOS). The committee diagnoses were embryonal (Emb) RMS in 877 (54%), alveolar (Alv) RMS in 343 (21%), botryoid (Botr) RMS in 88 (5%), pleomorphic (Pleo) RMS in 11 (1%), STI in 135 (8%), and EOE in 84 (5%). One in nine were mixtures of types, eg, Emb and Alv. Five percent of the sarcomas could not be classified because of inadequate material. In general, there was close agreement (94%) between the review committee and institutional pathologists in the diagnosis of RMS, but not in the specific types, particularly Alv RMS (41%) and STI (36%). This observation is important, since patients with Alv RMS and STI tumors had decreased survival compared with the other histologies. The prognosis varied by histology, with Botr having the best, Alv RMS and STI the worst, and Emb RMS and EOE an intermediate prognosis.

Age Factors↗

On the metabolism of ditazole in man.

This paper describes mass spectrometric studies on the metabolism of 4,5-diphenyl-2-bis-(2-hydroxyethyl)-amino-oxazole (ditazole, Ageroplas) in man. The metabolites were identified after cleavage of conjugates, extraction and derivatisation in urine of healthy volunteers orally administered with 400 mg of ditazole each. Besides the unchanged ditazole the following 7 metabolites could be detected: N-desalkyl and N,N-bisdesalkyl ditazole, hydroxy ditazole, N-desalkyl-hydroxy and N,N-bisdesalkyl-hydroxy ditazole as well as benzil and hydroxy benzil. Therefore, two main metabolic pathways, the aromatic hydroxylation and the N-desalkylation, can be postulated. Ditazole and its metabolites (with the exception of benzil) are excreted in urine partly in a conjugated form.

Biotransformation↗

Haemophilus influenzae type b immunization of children with sickle cell diseases.

Haemophilus influenzae type B vaccine is recommended for children 1.5 to 6 years of age with sickle cell anemia, but the adequacy of their response is unknown. A total of 69 children with sickle cell syndromes, 1.5 to 5.6 years of age, were immunized with two vaccines alternatively, single blind. PRP vaccine was given to 36 children and a diphtheria toxoid conjugated vaccine, PRP-D, was given to 36. Coded pre- and postvaccine sera were tested by radioimmunoassay for anti-PRP antibody. The groups did not differ in age distribution or type of sickle hemoglobinopathy. Preexisting antibody levels were low in both vaccine groups; 65% were less than 0.15 microgram/mL. The vaccines were safe but associated with frequent minor reactions. PRP-D gave higher geometric mean titers and mean fold titer increase than PRP in all children (15.58 micrograms/mL [234-fold] v 2.63 micrograms/mL [29-fold]) and in the subgroups 1.5 to 2.5 years of age or with pretiter values less than 0.15 microgram/mL. Titers for 64% of children receiving PRP and 94% receiving PRP-D were greater than or equal to 1.0 microgram/mL. Thus, both vaccines were useful in this population, but PRP-D was more immunogenic. Duration of antibody levels postvaccination, booster responses, and PRP-D immunogenicity in younger children with sickle cell syndromes all require further study.

Antibody Formation↗

Identification and differentiation of benzodiazepines and their metabolites in urine by computerized gas chromatography-mass spectrometry.

A method for the identification and differentiation of the following benzodiazepines and their metabolites in urine after acid hydrolysis and acetylation is described: bromazepam, camazepam, chlordiazepoxide, clobazam, clonazepam, clorazepate, clotiazepam, cloxazolam, delorazepam, diazepam, ethylloflazepate, flunitrazepam, flurazepam, halazepam, ketazolam, loprazolam, lorazepam, lormetazepam, medazepam, metaclazepam, midazolam, nitrazepam, nordazepam, oxazepam, oxazolam, prazepam, quazepam, temazepam and tetrazepam. The acetylated extract was analysed by computerized gas chromatography-mass spectrometry. An on-line computer allowed rapid detection using ion chromatography with ions m/z 205, 211, 230, 241, 245, 249, 312 and 333. The identity of positive signals in the reconstructed ion chromatogram was confirmed by a comparison of the stored full mass spectra with reference spectra. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (on OV-101) are documented.

Acetylation↗

Context of directives given to young children with Down syndrome and nonretarded children: development over two years.

The context in which directives are given in parent-child interactions was studied for 2 years in 6 families who had children with Down syndrome and 4 families with nonretarded children, beginning when the children were 12 months old. Comparisons were based on chronological, mental, and verbal age. Measures included implicit and explicit directives, children's moods, play behaviors, attention, and compliance behaviors. The hypothesis that all of these parents would give directives in similar situations was supported by the data. The differences found when the children were matched on CA essentially disappeared when MA was considered. All parents showed similar patterns of change over time, but for parents of children with Down syndrome, the significant changes often started 6 to 12 months later than for parents of nonretarded children.

Age Factors↗

Facial expressions of mentally retarded and nonretarded children: I. Recognition by mentally retarded and nonretarded adults.

Mentally retarded and nonretarded adults' ability to recognize happiness, anger, sadness, and neutral affect from slides of young mentally retarded and nonretarded children was investigated. Recognizing affects in others is part of social awareness and necessary for successful social interactions. Retarded adults recognized fewer facial expressions than did nonretarded adults. Nonretarded children's expressions were identified more accurately than were those of retarded children. Happiness was recognized best. Retarded adults used the label "happy" most often, whereas nonretarded adults used the label "neutral" most often. Absence of affect (neutral) was recognized least well by retarded adults. Neutral and sad were confounded most often by nonretarded adults, whereas retarded adults confounded angry and sad most often.

Adult↗

Facial expressions of mentally retarded and nonretarded children: II. Recognition by nonretarded adults with varying experience with mental retardation.

The influence of experience with mental retardation on nonretarded adults' ability to recognize facial expressions of emotion by young retarded children was examined. Four emotions were studied: happiness, anger, sadness, and neutrality (absence of affect). Slides of retarded and nonretarded children were presented to three groups: adults without experience in mental retardation, parents of retarded children, and teachers of the retarded stimulus children. Inexperienced adults identified fewer expressions of retarded children than did parents who, in turn, identified fewer expressions than did teachers. Teachers recognized expressions of retarded children best, inexperienced adults recognized expressions of nonretarded children best, and parents recognized expressions equally well in both retarded and nonretarded children. Happiness was recognized best in all children by all participants.

Adult↗

Localized orbital rhabdomyosarcoma. An interim report of the Intergroup Rhabdomyosarcoma Study Committee.

Children with rhabdomyosarcoma (RMS) (1461 total cases) were included in two prospective, randomized protocols conducted by the Intergroup Rhabdomyosarcoma Study (IRS) Committee from November 1972 to June 1983. Treatment assignment was determined by extent of tumor at diagnosis (clinicopathologic group) and not by primary site. Accordingly, 127 patients with RMS confined to the region of the eyelid and orbit were treated by a variety of regimens characterized by initial partial tumor resection followed by concurrent multiagent chemotherapy and orbital radiation therapy. Recurrent tumor developed in ten patients. Seven relapsed initially in the orbit (of whom 4 were salvaged) and three in regional nodes. In addition to the six patients who died of tumor, three died of other causes for a 93% 3-year actuarial survival rate. In 89 children who had subtotal resection or biopsy only, the local control rate with radiotherapy and chemotherapy was 94%.

Adolescent↗

Identification and differentiation of beta-blockers and their metabolites in urine by computerized gas chromatography-mass spectrometry.

A method for the identification and differentiation of beta-blockers and their metabolites in urine after acid hydrolysis is described. The acetylated extract is analysed by computerized gas chromatography-mass spectrometry. An on-line computer allows rapid detection using ion chromatography with the ions of m/z 72, 86, 98, 140, 151, 159, 200 and 335. The identity of positive signals in the reconstructed ion chromatogram is confirmed by a comparison of the stored entire mass spectra with the reference spectra. The ion chromatogram, the reference mass spectra and the gas chromatographic retention indices (OV-101) are documented. References for the quantitation of the single beta-blockers are cited.

Acetylation↗