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Biomedical subjects

J Hardt

Publications and source records attributed to J Hardt.

35 records · Page 2Linked to original sources
PubMed1999

Biological monitoring of exposure to pirimicarb: hydroxypyrimidines in human urine.

Pirimicarb (2-dimethylamino-5,6-dimethylpyrimidin-4-yldimethylcarbamate ) is used as insecticide in agriculture and fruit growing. During its metabolism in mammals the carbamate moiety is hydrolysed and subsequent demethylation at the dimethylaminogroup which is attached to the heterocyclic moiety results in the following major metabolites which are excreted in urine: 2-dimethylamino-5,6-dimethyl-4-hydroxypyrimidine (DDHP), 2-methylamino-5,6-dimethyl-4-hydroxypyrimidine (MDHP), and 2-amino-5,6-dimethyl-4-hydroxypyrimidine (ADHP). These metabolites were detected in every urine sample of seven workers who had applied pirimicarb. Concentrations of the MDHP and ADHP were much higher than that of DDHP indicating a considerable demethylation capacity in humans. No metabolites were found in urine specimens of controls. The investigated pyrimidines represent sensitive and specific parameters for biological monitoring of exposure to pirimicarb.

Carbamates↗
PubMed1999

Determination of urinary 2-thiazolidinethione-4-carboxylic acid after exposure to alkylene bisdithiocarbamates using gas chromatography-mass spectrometry.

This is a newly developed method which permits the quantitative determination of 2-thiazolidinethione-4-carboxylic acid (TTCA, an established biomarker of exposure to CS2) as a metabolite of alkylene bisdithiocarbamates (ABDCs) in human urine. After separation of TTCA from the urinary matrix using liquid-liquid extraction the analyte was converted into its diethyl derivative. Separation and quantitative analysis was carried out by capillary gas chromatography and mass selective detection in single ion monitoring mode. 4-(4-Chloro-2-methylphenoxy)butanoic acid (MCPBA) served as internal standard. The detection limit was 0.7 microg/l in urine. The relative standard deviation of the within-series imprecision was 4.3% at a concentration of 13 microg/l. The relative recovery was within the range of 86 to 98%. In order to determine the suitability of TTCA for biological monitoring after exposure to ABDCs, we analysed 87 24-h urine samples from occupationally exposed workers. The results were compared with the levels of TTCA excreted in urine by 50 control persons without known exposure to dithiocarbamates or CS2. This collective of unexposed persons also provided TTCA reference values for the general population. The urinary TTCA concentrations of the exposed persons were in the range from 0.8 microg/g creatinine to 515 microg/g creatinine. Unexposed persons excreted TTCA in concentrations from below the detection limit to 182 microg/g creatinine. The median concentration found in exposed persons (27 microg/g) was nearly 2.5 times higher than in non-exposed persons (11 microg/g). The difference between the exposed and unexposed collective was highly significant. Assessment of an individual's exposure by determining the level of TTCA in urine nevertheless was not possible. This was due to the relatively wide range of concentrations and because the ranges of both collectives overlapped.

Calibration↗
PubMed1999

Gas chromatographic method with mass-selective detection for the determination of 2-isopropoxyphenol in human urine.

Human metabolism of the insecticide propoxur yields 2-isopropoxyphenol (IPP) which is excreted conjugated in urine. In this publication a sensitive and selective analytical method is described which permits the determination of IPP as a suitable parameter for biomonitoring. The clean-up of the hydrolysed urine samples consisted of steam distillation and solid-phase extraction using a reversed-phase column. IPP and the internal standard 2-ethoxyphenol were converted to their pentafluorobenzyl ethers. Excess of the derivatisation reagent was removed using deactivated silica gel. Separation and quantitative analysis was carried out by capillary gas chromatography and mass selective detection. Coefficients of variation were below 5% for concentrations from 6 to 300 microg/l. The detection limit was 0.5 microg/l. The method was checked by analysing six urine samples from pest controllers after indoor application of propoxur. The IPP concentrations ranged from 45 to 306 microg/g creatinine. IPP was not detected in urine specimens from 10 non-exposed persons. The sensitivity of the developed method permits the detection of latent exposure to propoxur.

Gas Chromatography-Mass Spectrometry↗
PubMed1999

No changes in mood with the seasons: observations in 3000 chronic pain patients.

OBJECTIVE: Seasonal affective disorder (SAD) and the theory of the effect of light on depression have gained some popularity in recent years. Research on epidemiology is largely based on retrospective measures asking explicitly for the experience of seasonal variations. Those measures have a low positive predictive value and do not enable us to distinguish between experience and belief. METHOD: A consecutive sample of chronic pain patients filled out a depression questionnaire (CES-D) routinely as part of the diagnostic interview on becoming in-patients at a Pain Clinic in Mainz during a 5-year period. RESULTS: No support for seasonality or light effects was found. CONCLUSION: The effect of light on depression or seasonality may be smaller than expected in general. SAD as a true disorder is probably rare.

Affect↗
PubMed1997

Selection bias during recruitment of elderly subjects from the general population for psychiatric interviews.

The aim of the present study was to determine and assess a possible selection bias in an epidemiologic investigation in the elderly. A stratified sample of 1305 probands aged 60-99 years was initially contacted by mail and then by telephone to obtain their consent to participate in a psychiatric interview. A liberal recruitment procedure led to interview participation of only 291 subjects. The proportion of younger, male, and married subjects participating in the study was greater than that of elderly, female, and single or widowed subjects. Subjects without a psychiatric lifetime diagnosis were more cooperative than those with a psychiatric disorder. The latter finding demonstrates the need to determine and assess the selection bias in psychiatric epidemiologic studies in elderly subjects.

Aged↗
PubMed1996

Validity of the family history method in relatives of gerontopsychiatric patients.

It was the aim of the present study to evaluate the validity of the family history method in relatives of a sample of elderly subjects. A total of 201 relatives of patients and 89 relatives of control subjects were interviewed directly using the Composite International Diagnostic Interview and the Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, Multi-infarct Dementia and Dementias of other Etiology. At least one relevant other could provide family history information on a respective subject. Family history information for psychiatric disorders including dementia (DSM-III-R) was neither accurate, nor sensitive (10 to 40%), but highly specific (> 95%). The sensitivity of the family history for dementia and depression increased in relation to the severity of the disorder. Relatives of patients were better informants than relatives of controls (at least for the presence of any psychiatric disorder). The use of several informants only slightly improved the sensitivity of the family history, without reducing the specificity to a significant extent. The combination of different sources of information may serve to reduce information biases. The evaluation of possible biases in future family studies is required to draw adequate conclusions from differences in familial loads.

Adult↗
PubMed1996

A convenient method to discriminate between cytochrome P450 enzymes and flavin-containing monooxygenases in human liver microsomes.

Liver microsomes are a frequently used probe to investigate the phase I metabolism of xenobiotics in vitro. Structures containing nucleophilic hetero-atoms are possible substrates for cytochrome P450 enzymes (P450) and flavin-containing monooxygenases (FMO). Both enzymes are located in the endoplasmatic reticulum of hepatocytes and both need oxygen and NADPH as cofactors. The common method to distinguish between the two enzyme systems is to use the thermal inactivation of FMO and to inhibit P450 completely with carbon monoxide, N-octylamine or N-benzylimidazole. In the literature no indication could be found that the heat inactivation of FMO does not affect any of the human P450 enzymes or that the overall P450 inhibitors inhibit the different human P450 enzymes sufficiently and do not affect the FMO. The effect of N-benzylimidazole and heat inactivation was tested on specific activities of seven P450 enzymes in human liver microsomes, 1A2, 2A6, 2C9, 2C19, 2D6, 3A4/5, and 2E1, using methoxyresorufin O-demethylation, coumarin 7-hydroxylation, (S)-warfarin 4-hydroxylation, (S)-(+)-mephenytoin 4-hydroxylation, dextrometorphan O-demethylation, oxidation of denitronifedipine, and chlorzoxazone 6-hydroxylation respectively. The sulfoxidation of methimazole (MMI) was used as a specific probe for the determination of FMO activity. Methimazole sulfoxidation was compared with the well known assay for FMO metabolism, the formation of N,N-dimethylaniline (DMA) N-oxide, to be confirmed as an exclusively FMO mediated reaction. The participation of P450 and FMO in the sulfoxidation of four sulfur containing peptides, ametryne; terbutryne, prometryne and methiocarb was investigated using human liver microsomes. All four reactions were demonstrated to be catalysed predominantly by cytochrome P450.

Aniline Compounds↗
PubMed1994

Attentional abilities and measures of schizotypy: their variation and covariation in schizophrenic patients, their siblings, and normal control subjects.

Thirty-five schizophrenic patients in the early stages of illness, 26 of their healthy siblings, and 35 normal control subjects performed the Continuous Performance Test, Identical Pairs version (CPT-IP). Both schizophrenic patients and their siblings were significantly impaired in their attentional performance compared with normal subjects. These results support impaired attention as a vulnerability marker of schizophrenia and indicate that at-risk siblings of schizophrenic patients display attentional deficits comparable to those found for the offspring of schizophrenic parents. By contrast, a decline in performance with the onset of a distraction condition (auditory and visual stimuli) was seen only in schizophrenic patients; siblings and normal control subjects did not differ from one another in response to experimental distraction. Therefore, it was concluded that differential distractibility is likely to be a state marker of schizophrenia. In clinical assessments, healthy siblings rated themselves as experiencing significantly more physical anhedonia than did normal control subjects, but the siblings did not differ from normal control subjects in self-rated perceptual aberrations. Contrary to expectation, performance on the CPT-IP did not correlate significantly with either anhedonia or perceptual aberration in high-risk siblings. These results suggest that psychometrically measured "psychosis proneness" and neuropsychologically detected deficits may tap two nonoverlapping sources of vulnerability to schizophrenia.

Attention↗
PubMed1994

Reaction time paradigms in subjects at risk for schizophrenia.

Deviant response patterns in experimental reaction time paradigms in schizophrenic probands are well documented. Although simple reaction times are strongly influenced by the current psychopathological status of the proband (e.g. florid psychotic patients versus remitted patients) these influences are less clear for measures obtained from more complex reaction time paradigms. These include the crossover paradigm (reaction time to stimuli presented after constant preparatory intervals in comparison to reaction time to stimuli presented after irregular preparatory intervals) and the modality shift paradigm (reaction time to a stimulus (light or tone) when the modality of the stimulus on the preceding trial was the same compared to when it was different). It is not clear if these peculiarities of response patterns occur as a consequence of the disease or if they represent vulnerability markers for schizophrenia. Both crossover reaction time and modality shift reaction time paradigms were applied to 56 drug free schizophrenics, 45 healthy siblings of these patients and 68 healthy controls. The results indicate that retarded reaction times and the occurrence of the crossover effect as well as of the modality shift effect distinguish schizophrenics and controls. Healthy siblings of schizophrenics differed from healthy controls with regard to the crossover effect but not with regard to the modality shift effect. Therefore only the crossover effect represents a vulnerability marker for schizophrenia. Correlations between the modality shift and the crossover effect revealed strong correlations in the schizophrenic group only.

Adolescent↗
PubMed1993

Cognitive functioning and anhedonia in subjects at risk for schizophrenia.

This study investigated the performance of individuals with familiar loading of schizophrenia (healthy siblings of schizophrenic inpatients) on three neuropsychological tasks assumed to require frontal lobe functions: Trail Making Test (TMT), verbal fluency and Wisconsin Card Sorting Test (WCST). Healthy siblings of schizophrenics differed in performance from healthy controls not only on the WCST, but also on the Trail Making Test and the verbal fluency task. Furthermore, scores of physical anhedonia, assessed in a self-report rating scale (Chapman et al., 1976) were also significantly higher in the high risk group than in the control sample. However, healthy siblings of schizophrenics did not differ from controls with regard to experiences of perceptual aberrations, measured by the same method (Chapman et al., 1978). Neuropsychological performance and elevated anhedonia scores in the high risk group were interpreted under the conceptual framework of vulnerability markers: they were supposed to represent a trait shared by family members of schizophrenic probands. Amongst the neuropsychological tests, there were significant correlations between the physical anhedonia score and WCST and Trail Making test performance in the group of healthy siblings of schizophrenics, but not in the control group.

Adult↗
PubMed1993

Assessment of frontal lobe functioning in schizophrenia and unipolar major depression.

This study has used neuropsychological tasks--Wisconsin Card Sort (WCST), Trail Making (TMT) A and B, Verbal Fluency, Digit Span--to compare acute and currently off-medication schizophrenics, patients with unipolar nonpsychotic major depression and healthy controls. Both patient groups differed significantly from healthy controls in their neuropsychological performance. Furthermore there was only little (quantitative) difference between schizophrenics and depressed patients in the frontal lobe associated tasks: WCST, TMT and Verbal Fluency. Depressed patients tended to perform worse than schizophrenics on Digit Span, a task hypothesized to involve other than frontal areas of the brain. Although the group of depressed patients was older than the schizophrenic sample, the effect of age may not totally explain the findings. The results indicate that there do exist disturbances in frontal lobe cognitive functioning in schizophrenia and depression. Symptomatology (SANS/SAPS) and cognitive functioning in the schizophrenic group revealed only a trend for negative symptoms to be associated with worse performance in the WCST, but were significantly correlated with negative as well as positive symptoms on the TMT.

Adult↗
PubMedDate not supplied

Determination of dialkyl phosphates in human urine using gas chromatography-mass spectrometry.

Organophosphates are used as pesticides in agriculture and pest control. They are metabolized to dialkylphosphates, which are excreted in urine. Determination of these metabolites is useful for assessing human exposure to organophosphates. This publication describes a new, reliable, and very sensitive analytical procedure for quantitating dimethylphosphate (DMP), diethylphosphate (DEP), O,O-dimethylthiophosphate (DMTP), O,O-diethylthiophosphate (DETP), O,O-dimethyldithiophosphate (DMDTP), and O,O-diethyldithiophosphate (DEDTP) in human urine. The analytes are extracted from acidified urine into a mixture of diethylether and acetonitrile. Dibutylphosphate serves as internal standard. Derivatization is performed using pentafluorobenzylbromide at 40 degrees C overnight. After further liquid-liquid extraction, analysis is carried out by gas chromatography-mass spectrometry. The limits of detection are 5 microg/L urine for DMP and 1 microg/L for the other five metabolites. Using the new procedure, 54 spot urine samples from persons in the general population in Germany were analyzed. Nearly every sample contained DMP, DEP, and DMTP, and the median values (95th percentiles) of the concentrations were 30 microg/L (105 microg/L), 4 microg/L (21 microg/L), and 22 microg/L (174 microg/L), respectively. DETP and DMDTP were found in lower concentrations.

Environmental Monitoring↗