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W Maier

Publications and source records attributed to W Maier.

At least 127 records · Page 7Linked to original sources

A family-based study of the Cys23Ser 5HT2C serotonin receptor polymorphism in schizophrenia.

The 5HT2C receptor has a high affinity for clozapine, a nontypical neuroleptic, and has therefore been postulated to play a role in mediating negative symptoms and neuroleptic response in schizophrenia. In the current study, the Cys23Ser 5HT2C serotonin receptor polymorphism was examined for linkage to schizophrenia by genotyping 207 nuclear families consisting of both parents and schizophrenic child and using the transmission disequilibrium test to examine possible preferential transmission of these alleles from 68 heterozygous mothers to their ill child. No evidence was obtained for preferential transmission of the Cys23Ser 5HT2C alleles in schizophrenia in either of the two main ethnic groups examined (German and Palestinian Arab) or in the combined cohort (TDT chi-square = 0.00, NS).

Adolescent↗

ABC stenosis morphology classification and outcome of coronary angioplasty: reassessment with computing techniques.

BACKGROUND: The American College of Cardiology/American Heart Association (ACC/AHA) stenosis morphology classification (MC) stratifies coronary lesions for probability of success and complications after coronary angioplasty (PTCA). Modern computing techniques were used to evaluate the individual predictive value of MC in random PTCA cases. METHODS AND RESULTS: MC was attributed to the target lesions by consensus of 2 observers. The predictive value regarding procedural success (PS) and major adverse cardiac events (MACE) of MC was analyzed by conventional logistic regression analyses and by inductive machine learning models. The study was adequately powered for the methods applied with 325 target lesions of 250 cases. Overall, PS decreased and MACE increased from type A to type C lesions. Regression analysis identified no single factor as predictive. Logistic regression showed an error rate of 42%. Machine learning techniques achieved an individual predictive error of only 10%, which could be further reduced to 2% by addition of parameters. For PS, MC parameters showed a high ranking for building the model. For MACE, variables of the medical history showed more impact. CONCLUSIONS: MC per se cannot individually predict PS or MACE. However, when all MC parameters are integrated together with additional lesion-specific and history variables, a high individual predictive value can be achieved. This technique may be clinically helpful for risk stratification in the catheterization laboratory and improvement of classification systems in interventional cardiology.

Algorithms↗

Nonreplication of association between mu-opioid-receptor gene (OPRM1) A118G polymorphism and substance dependence.

In the present investigation we hypothesized the A118G (Asn40Asp) polymorphism of the mu-opioid receptor gene (OPRM1) as a particular vulnerability factor for heroin and alcohol dependence. Therefore, we tested this hypothesis in two independent large samples by two different methods: a case-control sample (comprising n = 287 heroin and n = 221 alcohol study subjects versus n = 365 nondependent controls) and a family-controlled sample of 111 parent-offspring trios of heroin-dependent study subjects and 75 parent-offspring trios of alcohol-dependent study subjects to avoid stratification artifacts. In both patient samples and by both methods we were unable to corroborate the hypothesis of OPRM1 A118G polymorphism as a particular risk factor for any kind of substance dependence including opioid addiction. In addition, there was no significant association between the endophenotype of the individuals under study (e.g., comorbidity, severity of illness) and a particular genotype of OPRM1.

Adenine↗

A family study of Alzheimer disease and early- and late-onset depression in elderly patients.

BACKGROUND: The substantial symptomatic overlap between depression and dementia in old age may be explained by common genetic vulnerability factors. METHODS: We investigated this idea by comparing the occurrence of both disorders in first-degree relatives of 78 patients with Alzheimer disease (AD), of 74 with late-onset depression (onset age of > or = 60 years), of 78 with early-onset depression, of 53 with comorbid lifetime diagnoses of AD/depression, and of 162 population control subjects. Diagnostic information on their 3002 relatives was obtained from structured direct assessments and from family history interviews. RESULTS: The 90-year lifetime incidence of primary progressive dementia was significantly higher in relatives of patients with AD (30%) and comorbid AD/depression (27%) than in relatives of patients with early-onset (21%) or late-onset (26%) depression, or of controls (22%) (P =.01). Lifetime incidence of depression was significantly higher in relatives of patients with early-onset depression (13%) than in relatives of patients with AD (10%) or controls (9.0%) (P =.006). Lifetime incidence of depression was similar in control relatives and in relatives of those patients with comorbid AD/depression (8.6%). Relatives of patients with late-onset depression also showed similar occurrence of depression until the age of 80 years, but the figure increased sharply thereafter to 19.1% by the age of 90 years. CONCLUSIONS: Primary progressive dementia and early-onset depression represent clinical entities with distinct inheritance. Late-onset depression does not share substantial inheritance in common with dementia or with early-onset depression, but does show modest familial clustering.

Age Factors↗

Mind reading: neural mechanisms of theory of mind and self-perspective.

Human self-consciousness as the metarepresentation of ones own mental states and the so-called theory of mind (TOM) capacity, which requires the ability to model the mental states of others, are closely related higher cognitive functions. We address here the issue of whether taking the self-perspective (SELF) or modeling the mind of someone else (TOM) employ the same or differential neural mechanisms. A TOM paradigm was used and extended to include stimulus material that involved TOM and SELF capacities in a two-way factorial design. A behavioral study in 42 healthy volunteers showed that TOM and SELF induced differential states of mind: subjects assigned correctly first or third person pronouns when providing responses to the stimuli. Following the behavioral study, we used functional magnetic resonance imaging (fMRI) in eight healthy, right-handed males to study the common and differential neural mechanisms underlying TOM and SELF. The main factor TOM led to increased neural activity in the anterior cingulate cortex and left temporopolar cortex. The main factor SELF led to increased neural activity in the right temporoparietal junction and in the anterior cingulate cortex. A significant interaction of both factors TOM and SELF was observed in the right prefrontal cortex. These divergent neural activations in response to TOM and SELF suggest that these important differential mental capacities of human self-consciousness are implemented at least in part in distinct brain regions. Press

Adult↗

Identification of items which predict later development of depression in primary health care.

To improve recognition and treatment of depression in primary care it would be advantageous to have criteria for identification of later depression. Only a few studies were performed on primary care samples to examine risk factors for new depressive episodes. These were mostly cross-sectional and did not include psychiatric symptoms as possible predictors. This is the first one-year-follow-up study investigating prospectively psychiatric symptomatology as risk factors for depressive episodes in a primary care sample. An international primary care sample of initially non-depressed subjects (n = 2,445) was examined for the presence of depression (ICD-10) at follow-up. Initial measures addressed presence of psychiatric symptoms according to the CIDI-Primary Health Care Version and sociodemographic variables. Logistic regression analysis was carried out to determine the relationship with the development of new depressive episodes. After one year, 4.4% of primary care patients met ICD-10 criteria for a depressive episode. Logistic regression analysis revealed that symptoms of depression and physical, mainly pain-related symptoms were associated with depression at follow-up. General practitioners therefore should be careful in the consideration of depressive symptoms but also of somatic complaints which might precede depression or mask depressive symptomatology. The present results might be helpful for future development of prediction scales.

Adolescent↗

[Structural brain changes in patients with schizophrenic psychoses. From focal pathology to network disorder].

Schizophrenia is a brain disorder characterized by a heterogeneous clinical symptomatology. Accordingly, many structural brain changes are not associated directly with clinical symptoms. These structural changes can be detected in the frontotemporal cortex and may correlate with the course of the disease. The most important etiological concept is the neurodevelopmental hypothesis according to which developmental, morphologically detectable changes predispose for the acquisition of schizophrenia. The relevance of neurodegenerative components also remains to be determined. However, it is becoming increasingly clear that schizophrenia is not associated with pathological changes in a circumscribed brain region but with widely distributed morphological changes. Presently, the leading hypothesis for explaining these changes is a frontotemporolimbic network disturbance with cytoarchitectural changes in the heteromodal association cortex. Present research therefore focuses on testing this theory using functional imaging on a macroscopic level and examination of the neuronal cytoarchitecture on a microscopic level.

Brain↗

An economic model of the long-term health care burden of Type II diabetes.

AIMS/HYPOTHESIS: To develop a long-term economic model of health care for Type II diabetes initially for the United Kingdom; characterize experiences of diabetes-related morbidities and the use of health care resources among a typical Type II diabetes cohort; to estimate lifetime differences in expected health outcomes and costs attributable to Type II diabetes; and to facilitate evaluation of policies or interventions in treating Type II diabetes from the funder's perspective. METHODS: A compact spreadsheet structure of interconnected Markov chain modules was developed to facilitate rapid estimation of costs and outcomes for whole populations. Recent clinical findings from the United Kingdom Prospective Diabetes Study and other sources were incorporated and a detailed costing module developed from United Kingdom observational data. RESULTS: The model allows the assessment of costs and long-term complications experienced by people suffering from Type II diabetes, including direct health care costs associated with the main diabetic complications and second-order effects on other health services required by such patients. Initial results suggest that the lifetime cost of health care for patients from the diagnosis of diabetes is more than double that for an equivalent non-diabetic population. CONCLUSION/INTERPRETATION: The model is intended for use by health care policy makers and payers to assess the long-term budgetary impact of trends in a variety of demographic and epidemiological factors on future services, and is also useful to physicians when considering the impact of new treatment strategies or programmes to modify risk factors for diabetic complications.

Adult↗

Influence of CYP2D6 genotype and medication on the sparteine metabolic ratio of psychiatric patients.

OBJECTIVE: To investigate the influence of CYP2D6 genotype and medication on the reliability of phenotyping in a naturalistic setting of psychiatric inpatients. METHODS: The phenotype of 160 psychiatric inpatients was estimated by taking the urinary metabolic ratio (MR) of the concentrations of sparteine to 2- and 5-dehydrosparteine. Genotyping identified CYP2D6*1, *3, *4, *5 and *6 alleles as well as duplication of the CYP2D6 gene. All subjects underwent detailed drug history including drug dose and therapeutic drug monitoring to control compliance and abuse of other psychotropic drugs. These data were compared with those of 195 unmedicated healthy Germans. RESULTS: The cumulative distribution of the MR in patients showed a significant shift to higher MR when compared with that of healthy subjects (P < or = 0.001). Patients medicated either with selective serotonin reuptake inhibitors (SSRIs, P < or = 0.001), antipsychotic drugs (P= 0.002) or other drugs known to be substrates or inhibitors of CYP2D6 (P < or = 0.001) showed a significantly higher mean MR than unmedicated patients. However, there was no significant effect of tricyclic antidepressants on the MR. Healthy subjects with CYP2D6 deficiency were separated by a MR of greater than 20 from those who expressed functional CYP2D6. Seven patients carrying at least one functional CYP2D6 allele revealed a MR of greater than 20, indicating the occurrence of phenocopying. CONCLUSION: The results of phenotyping may be falsified by drugs known to be substrates or inhibitors of CYP2D6; thus, this method is not sufficiently reliable. However, since we observed the phenomenon of phenocopying only in patients treated with a SSRI such as fluoxetine, fluvoxamine or paroxetine, we conclude that sparteine phenotyping of medicated patients detects CYP2D6 deficiency correctly, provided that patients treated with these SSRIs are excluded.

Adult↗

Clinical evaluation of a new stationary high strip density antiscatter grid in comparison with a conventional moving grid: influence on image quality and patient radiation dose.

This study aimed to evaluate a new stationary 13/75 antiscatter grid in comparison with a moving 12/40 grid with regard to its influence on image quality and patient radiation dose. One hundred consecutive patients had plain films of the abdomen using a moving 12/40 grid and another 100 patients were examined with a stationary 13/75 grid (tube voltage 73 kV, film size 35 cm x 43 cm, film-screen system speed class 400). As an intraindividual comparison, radiographs of the abdomen with a film size of 18 cm x 43 cm were taken of 27 patients using both grid types for every patient. Patients' weight and dose-area product were recorded. Image quality was evaluated by a multireader study using standardized questionnaires and three- or five-level grading systems. Results showed that use of the 13/75 grid accords with the ALARA principle: measurement of the dose-area product demonstrated a dose saving of 24% for a film size of 35 cm x 43 cm and a saving of 34% for a film size of 18 cm x 43 cm without calling into question the diagnostic image quality. The mean scores of the 12/40 grid were lower for three out of six normal anatomic structures (P<0.05) among the 200 patients, indicating a loss of image quality with the 13/75 grid. Assessment of the intraindividual trial revealed reduced detectability of three out of four anatomical details when the 13/75 grid was employed. At the cost of a minor loss of image quality in comparison with the 12/40 grid, the new stationary grid provides a clear reduction of radiation dose under clinical circumstances.

Aged↗

Major psychoses symptomatology: factor analysis of 2241 psychotic subjects.

Current nosography classifies major psychoses as separate disorders, but their symptomatological presentation during illness episodes largely overlaps and diagnoses may change during a lifetime. Few analyses of major psychoses symptomatology have been performed so far because of the large number of subjects needed to obtain stable factors. The purpose of this study was, therefore, to identify the symptomatologic structure common to major psychoses based on lifetime symptoms. Two thousand and forty-one inpatients affected by schizophrenic (n=1008), bipolar (n=563), major depressive (n=352), delusional (n=108) and psychotic not otherwise specified disorder (n=210) were rated for lifetime symptoms using the Operational Criteria Checklist for Psychotic Illness (OPCRIT) and included in a factorial analysis. Four factors were obtained, the first consisted of excitement symptoms, the second comprised psychotic features (delusions and hallucinations), the third comprised depression and the fourth disorganization. When scored by the OPCRIT checklist, major psychoses symptomatology is composed of excitement, depressive, delusion and disorganization symptoms.

Adult↗

Effect of drugs inhibiting spermidine biosynthesis and metabolism on the in vitro development of Plasmodium falciparum.

Treatment of Plasmodium falciparum with the potent inhibitor dicyclohexylamine completely arrests in vitro cell proliferation of the chloroquine-susceptible P. falciparum strain NF54 and the R strain, which shows less sensivity to chloroquine. The average inhibitory concentration (IC50) values determined for both strains revealed different inhibition profiles. The IC50 value for the chloroquine-sensitive NF54 strain was 97 microM and 501 microM for the R strain. Monitoring polyamine pools after treatment with dicyclohexylamine leads to a significant decrease in the intracellular spermidine content, which was nearly reversed by supplementation with spermidine. Since spermidine is an important precursor for the biosynthesis of hypusine and homospermidine in eukaryotes, we studied the developmental effect on both P. falciparum strains of 1,7-diaminoheptane as an inhibitor of deoxyhypusine synthase (EC 1.1.1.249) in mammalian cells, and agmatine as a moderate inhibitor of homospermidine synthase (EC 2.5.1.44). Inhibition profiles with 1,7-diaminoheptane resulted in an IC50 value of 466 microM for the NF54 strain and 319 microM for the R strain. Spermidine pools changed significantly. Inhibition with agmatine caused a strong decrease in parasitemia for the chloroquine-susceptible NF54 strain, with a determined IC50 value of 431 microM and an IC50 value of 340 microM for the less chloroquine-susceptible R strain. Spermidine was not detectable after inhibition. The uncommon triamine homospermidine occurred in both P. falciparum strains. To our knowledge this is the first evidence of homospermidine in P. falciparum. The use of specific inhibitors of spermidine metabolism might be a novel strategy for the design of new antimalarials, and suggests the occurrence of both enzymes in the parasite.

Agmatine↗

Affective symptomatology in schizophrenia: a risk factor for tardive dyskinesia?

Affective symptomatology has repeatedly been suggested to confer susceptibility to tardive dyskinesia (TD). In our sample of 174 schizophrenic patients a history of depressive symptoms was not associated with the occurrence of TD, whereas manic symptomatology was significantly associated with the absence of TD. Thus, our data suggest that affective symptomatology cannot unambiguously be considered to predispose to TD.

Adult↗

Seasonal distribution of births in patients with Alzheimer's disease and elderly depressive patients.

Winter births have been associated with a higher risk of Alzheimer's disease (AD) and other psychiatric disorders. In the present investigation, this putative association was examined in a sample of gerontopsychiatric patients. An analysis of the quarterly birth rates of 83 patients with AD, 78 elderly depressive patients with an early onset and 74 patients with a late onset of the depressive disorder, 48 patients with both AD and depression (co-morbid patients) and 107 healthy control subjects, revealed no particular seasonal distribution for any of the diagnostic groups. In AD and co-morbid patients, controlling for the ApoE genotype did not change this finding. Logistic regression analysis revealed the expected findings that increasing age and the presence of the ApoE4 allele were associated with a higher risk of dementia. Younger age and female gender were identified as risk factors for a depressive disorder. A winter birth (birth in the first three months of the year) was not associated with any of the diagnostic subgroups. We concluded that in our sample a seasonal distribution of births was not found to increase the risk for AD or geriatric depression.

Age Distribution↗

Familial occurrence of tardive dyskinesia.

OBJECTIVE: Familial occurrence of tardive dyskinesia (TD) and schizophrenia has been hypothesized to confer risk to the development of TD. We investigated these hypotheses in a large patient sample applying standardized methods for phenotype characterization. METHOD: Two hundred and twenty-two patients with a diagnosis of schizophrenia or schizoaffective disorder were assessed for TD and for family history of schizophrenia or schizoaffective disorder. Thirty-nine patients had 40 affected first-degree family members, one patient having two first-degree relatives. Of these, 17 pairs and one triplet were personally examined. RESULTS: 1) There was a tendency for TD in the affected relatives to be associated with the TD status of the index-patient; this finding was unrelated to age and doses of neuroleptic medication. 2) No association between a family history of schizophrenia or schizoaffective disorder and TD was found. CONCLUSION: A family history of TD might represent a risk factor for TD, whereas a family history of schizophrenia does not.

Adult↗