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Biomedical subjects

W Maier

Publications and source records attributed to W Maier.

At least 145 records · Page 8Linked to original sources
PubMed2001

Association analysis of NOTCH4 loci in schizophrenia using family and population-based controls.

A genetic association between NOTCH4 and schizophrenia has previously been proposed. Unsing all markers previously shown to be associated, we found no evidence for such in three independent family-based samples (n=519 parent-offspring trios), and a case-control sample derived from the same ethnic background as the original observation. These data strongly suggest that NOTCH4 is not a significant susceptibility allele for schizophrenia.

Case-Control Studies↗
PubMed2001

Association study of the low-activity allele of catechol-O-methyltransferase and alcoholism using a family-based approach.

Catechol-O-methyltransferase (COMT) is a major component of the metabolic pathways of neurotransmitters such as dopamine, adrenaline, and noradrenaline. The activity of COMT is known to vary within the population; it exists in common high- and low-activity forms that are determined by a Val --> Met polymorphism at amino acid position 108/158 (in soluble or membrane-bound COMT). Recently, the low-activity allele was reported to contribute to the development of late-onset alcoholism in men. The present study extends this study by utilizing a family-based association approach, and by including individuals with early-onset alcoholism. Although no significant transmission disequilibrium was found in the overall sample of 70 parent/offspring trios (TDT = 1.43, P = 0.23), we observed a preferential transmission of the low-activity allele to patients with an early onset of disease (n = 32, TDT = 4.83, P = 0.028). Our results provide further evidence for an involvement of the COMT low-activity allele in the development of alcoholism and demonstrate the need for further studies in large samples of alcoholic patients.

Adult↗
PubMed2001

A possible susceptibility locus for bipolar affective disorder in chromosomal region 10q25--q26.

In an attempt to identify susceptibility loci for bipolar affective disorder, we are currently conducting a systematic genome screen with highly polymorphic microsatellite markers at an average marker spacing of 10 cM in a series of 75 families, comprising 66 families from Germany, eight families from Israel, and one family from Italy. The families were ascertained through index cases with bipolar affective disorder. The distribution of diagnoses is as follows: 126 individuals with bipolar I disorder, 40 with bipolar II disorder, 14 with schizoaffective disorder of the bipolar type, 40 individuals with recurrent unipolar depression, 51 with a minor psychiatric diagnosis, and two individuals with a diagnosis of schizophrenia. One hundred and seventy-one individuals are unaffected. Here, we present results from chromosome 10. Linkage analyses using a total of 33 microsatellite markers with parametric and non-parametric methods provided evidence for linkage at chromosomal region 10q25--q26. The highest two-point LOD score (2.86, theta = 0.05) was obtained for D10S217 using a dominant genetic model and a broad definition of affection status. The GENEHUNTER program localized the putative susceptibility locus within a ca 15-cM interval between markers D10S1483 and D10S217 with a maximum NPL(all) score of 3.12 (P = 0.0013). Positive linkage findings that have been reported by two independent studies further support the hypothesis of a susceptibility gene for bipolar affective disorder on 10q25-q26.

Bipolar Disorder↗
PubMed2001

Evolution of percutaneous transluminal coronary angioplasty in Europe from 1992-1996.

BACKGROUND: The working group Coronary Circulation of the European Society of Cardiology has been conducting a yearly survey on coronary interventions in Europe. The purpose of this study is to present the evolution of percutaneous transluminal coronary angioplasty (PTCA) with epidemiological and economic implications. METHODS: Coronary interventions were polled by questionnaires distributed to all institutions performing cardiac catheterization. Aggregated country data of the years 1992-1996 on indication, type of procedure, technique, and outcome of coronary interventions were analysed. RESULTS: Population-adjusted coronary angiographies and PTCA procedures increased by 76% and by 105%, respectively. The Percentage of coronary stenting increased from zero to almost half of all procedures. Analysis per country groups reveals considerable variation, ranging, e.g. for PTCA in 1996 from 157 procedures per million population in a group of eastern countries to 1138 in a central European group. Relating total revascularization (R) to standardized death rate for ischaemic heart disease (SDR) and to gross domestic product (GDP), there was an increase from 1.0 to 1.8 R/SDR and 40 to 61 R/GDP in the central European group compared with an increase from 0.06 to 0.18 R/SDR and 43 to 85 R/GDP in the eastern group. CONCLUSIONS: An overall increase in PTCAs at an annual rate between 15 and 25% was observed. The wide variation in the use of PTCA in Europe appears to be dependent mostly on economic factors and national health care policies.

Angioplasty, Balloon, Coronary↗
PubMed2001

Serotonin receptor gene HTR3A variants in schizophrenic and bipolar affective patients.

Serotonin receptor genes have always been considered excellent candidate genes in the aetiology of neurogenetic diseases. In this study, we assessed sequence variations of the HTR3A gene. For this purpose, we established exon-specific primers and analysed DNA samples from 165 unrelated individuals including 70 schizophrenic patients, 48 patients with bipolar affective disorder and 47 healthy control persons using polymerase chain reaction/single-strand conformational polymorphism analysis. We discovered six sequence variants, five of which represent polymorphisms. These polymorphisms could not be associated with schizophrenia and bipolar affective disorder (P = 0.055-1). We also detected a missense mutation in exon 9 in a schizophrenic patient at a conserved position (Pro391Arg). To determine the incidence of this substitution an extended set of 358 schizophrenic patients and 155 control individuals was investigated. The Pro391Arg mutation was not detected in these schizophrenic patients and controls screened. However, a second missense mutation (Arg344His) was detected in one schizophrenic patient, but not in any of the controls. These results suggest that the observed mutations in HTR3A are rare and therefore do not play a major role in the aetiology of the disorder. Further studies are needed to support the hypothesis that HTR3A may contribute to the schizophrenia in these patients.

Adult↗
PubMed2001

Brainstem response in cerebellopontine angle tumors.

OBJECTIVE: To evaluate the auditory brainstem response (ABR) findings in cerebellopontine angle (CPA) tumors and focus on those with normal ABR results. STUDY DESIGN: This was a retrospective evaluation of ABR findings. All subjects with diagnosed CPA tumors who were referred for treatment were included. PATIENTS: All 309 patients with radiographically confirmed (computed tomography or magnetic resonance imaging [MRI]) CPA tumors (153 before 1993 and 156 after 1993). INTERVENTION: All patients underwent complete audiologic examination, electronystagmography, ABR testing, and ipsilateral transtympanic electrocochleography. All tumors were histologically confirmed. MAIN OUTCOME MEASURES: The patients were categorized according to ABR results (normal or pathologic findings or no response); according to histology (vestibular schwannomas or meningiomas); and according to tumor size by MRI (small, up to 15 mm; medium, 16-25 mm; large, 26-40 mm; and very large, over 40 mm). RESULTS: Normal ABR results were found in 18.4%; pathologic ABR results in 31.4%; and no response in 50.2%. Small vestibular schwannomas (under 15 mm) showed a higher incidence of normal ABR results (41.7%). CPA tumors with normal ABR results (n = 57) caused no hearing loss (n = 12), symmetrical hearing loss (n = 11), or ipsilateral hearing loss with Short Increment Sensitivity Index 100% and normal acoustic reflex (cochlear deafness, n = 34). Caloric response was normal in 59.7% of these tumors. CONCLUSION: Because validation of ABR as screening for acoustic tumors is based on diagnosed tumors, and because MRI allows detection of very small tumors, the incidence of normal ABR increases and its sensitivity would be expected to decrease. ABR is not sufficient for early detection of small CPA tumors.

Audiometry, Evoked Response↗
PubMed2001

Right frontal hypergyria differentiation in affected and unaffected siblings from families multiply affected with schizophrenia: a morphometric mri study.

OBJECTIVE: The authors used magnetic resonance imaging to corroborate the postmortem finding of right frontal hypergyria associated with schizophrenia. METHOD: Twelve affected-unaffected sibling pairs from families multiply affected with schizophrenia were studied. Bilateral measurement of the gyrification index, the ratio of the inner and outer surface contours, was performed on three different slices of the prefrontal region. RESULTS: The mean gyrification index on the right side was significantly higher in siblings with schizophrenia or schizoaffective disorder than in the unaffected siblings. CONCLUSIONS: In this family cohort study, the postmortem finding of right-sided hypergyria in subjects with schizophrenia was replicated in vivo with magnetic resonance imaging. This observation provides further support for a neurodevelopmental mechanism in the pathogenesis of schizophrenia.

Adult↗
PubMed2001

Subcortical correlates of craving in recently abstinent alcoholic patients.

OBJECTIVE: This study investigated functional cerebral correlates of craving in alcoholic patients and examined the state/trait characteristics of the regional cerebral network implicated in craving. METHOD: Functional magnetic resonance imaging (fMRI) was used to map cerebral response elicited by ethanol odor in 10 male patients with alcohol dependence who had undergone detoxification and 10 matched nonpatients. After 3 weeks, during which the patients underwent standardized behavioral therapy with psychopharmacological intervention, all subjects were studied a second time with fMRI to evaluate the effects of therapy on the functional cerebral correlates of craving. RESULTS: In the alcoholic patients, cue-induced craving before treatment elicited activation primarily in the subcortical-limbic region of the right amygdala/hippocampal area and in the cerebellum. After treatment, activation was found in the superior temporal sulcus, while subcortical or cerebellar participation was no longer present. Comparison subjects showed no comparable amygdala or cerebellar activation during ethanol stimulation and demonstrated no change in activation pattern between measurements. CONCLUSIONS: This investigation points to state-dependent neurobiological correlates of cue-induced craving in alcoholic patients and suggests that these correlates can be influenced by therapeutic interventions. The presence of emotional aspects of craving is suggested by amygdala activation.

Adult↗
PubMed2001

Sensory gating deficit expressed by a disturbed suppression of the P50 event-related potential in patients with Alzheimer's disease.

OBJECTIVE: Disturbed sensory gating has been related to attention deficit and greater distractibility in patients with schizophrenia, and dysfunction of the alpha-7 subunit of the cholinergic nicotinic receptor has been discussed as its biological basis. Alzheimer's disease is characterized by a cholinergic deficit, and postmortem studies have reported alpha-7 receptor loss in patients with Alzheimer's disease. In this study, the authors tested whether sensory gating is disturbed in patients with Alzheimer's disease. METHOD: Suppression of the P50 event-related potential following the second click of a double-click paradigm, a measure of sensory gating, was assessed in 17 Alzheimer's disease patients and 17 comparison subjects. RESULTS: Alzheimer's disease patients showed less P50 suppression following the second click relative to the comparison subjects. CONCLUSIONS: Disturbed sensory gating might result from cholinergic dysfunction and possibly from alpha-7 nicotinic receptor loss in patients with Alzheimer's disease. Prospective studies should investigate the relationship between sensory gating deficit and behavioral disturbances in Alzheimer's disease patients.

Acoustic Stimulation↗
PubMed2000

Pharmacogenomics and addiction to opiates.

The risk of initiating and maintaining the use of opiates up to the point of abuse and dependence is to a large degree genetically transmitted and is separate from genetic risk factors for addiction to other drugs of abuse. Pharmacogenetic studies have so far focused on obvious candidate genes that are expected to be involved either in the pharmacokinetics or in the pharmacodynamics of opioids in the mesolimbic reward system of the brain. The few findings of a positive allelic association rarely withstand replication in independent case-control or less stratification-prone family-based association samples. A pharmacogenomic approach in the best sense of the word, however, involves an unbiased, genome-wide, parallel search for risk genes and gene expression patterns. So far, only quantitative trait loci mapping studies of inbred rodent strains and differential expression studies using high-density DNA microarrays fulfill these requirements. The present state of pharmacogenomic and pharmacogenetic studies in animals and humans with respect to opiate addiction is reviewed in this paper.

Animals↗
PubMed2000

Identical distribution of the alpha 2-macroglobulin pentanucleotide deletion in subjects with Alzheimer disease and controls in a German population.

Recently, an association between a deletion polymorphism in the alpha 2-macroglobulin gene (A2M) and Alzheimer disease (AD) has been reported. The aim of the present study was to corroborate this association in a German population of 102 AD patients and two control samples of 191 healthy subject and 160 depressed patients. The frequency of the A2M genotype in AD patients was almost identical to that in both control samples. Logistic regression analysis revealed an effect of age and the APOE genotype on AD risk, but no effect of the A2M genotype. Our findings do not support the fact that the previously reported positive association between A2M deletion polymorphism and AD modifies the disease risk in the studied population. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:775-777, 2000.

Aged↗
PubMed2000

No association between the dopamine D3 receptor Bal I polymorphism and schizophrenia in a family-based study of a Palestinian Arab population.

Several recent meta-analyses appear to show a weak but significant effect of both forms of the gly/ser DRD3 polymorphism in conferring risk for schizophrenia. Since most studies have employed the artifact-prone case-control design, we thought it worthwhile to examine the role of this polymorphism using a robust family-based strategy in an ethnic group not previously systematically studied in psychiatric genetics, Palestinian Arabs. We failed to obtain any evidence in 129 Palestinian triads, using the haplotype relative risk (allele frequency: Pearson chi-square = 0.009, P > 0.1, df = 1, n = 258 alleles) or transmission disequilibrium test design (chi-square = 0.38, P > 0.1, n = 86 families) for association/linkage (or increased homozygosity) of the DRD3 Bal I polymorphism to schizophrenia in our sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:778-780, 2000.

Alleles↗
PubMed2000

Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder.

Various polymorphisms of the X-chromosomal monoamine oxidase A (MAO-A) gene were investigated for association with affective disorders. However, none of the studied variants could consistently be associated with either major depressive or bipolar affective disorder. Recently, a positive association between panic disorder and a novel functional repeat polymorphism in the MAO-A gene promoter, with the longer alleles being more active, was reported. Since monoaminergic neurotransmission is supposed to play an important role in affective disorders, we investigated a potential association of this polymorphism with major depressive illness in a sample of 146 unrelated patients of German descent and a control group of 101 individuals with a negative life history for affective disorders. Similarly to the recent findings in panic disorder, we observed a significantly increased frequency of genotypes containing only long alleles in female patients with recurrent major depression in comparison with age- and sex-matched controls. Thus, our data suggest that an excess of high-activity MAO-A gene promoter alleles resulting in an elevated MAO-A activity is a risk factor for major depressive disorder in females. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:801-803, 2000.

Adult↗
PubMed2000

Use of an emboli containment and retrieval system during percutaneous coronary angioplasty in native coronary arteries.

BACKGROUND: Prevention of distal embolisation during percutaneous coronary revascularisation may be necessary to reduce postinterventional morbidity and mortality. METHODS AND RESULTS: We employed a newly developed emboli containment and retrieval system in native coronary arteries during percutaneous coronary angioplasty and stenting in 39 selected patients (mean age 58.9 +/- 10.1 years, 11 females) presenting with acute (n = 22; 8 LAD, 3 LCX, 11 RCA), subacute (n = 7; 2 LAD, 2 LCX, 3 RCA) or chronic (n = 6; 2 LAD, 4 RCA) total or subtotal occlusion of an infarct-related vessel, or with severe stenosis and symptoms of unstable angina (n = 4; 2 LAD, 2 RCA). Protection device-assisted angioplasty with stent implantation was uneventful in all patients with good angiographic results and normal postprocedural flow. Intermittent aggravation of anginal pain during inflation of the occlusive balloon (from 2.5 to a maximum of 25 minutes cumulative inflation time) was observed in 19 of the 36 conscious patients (7 with acute, 7 with subacute and 3 with chronic occlusion, and 2 with unstable angina), but caused neither interruption of distal occlusion nor haemodynamic instability. In 31 patients the aspirates contained visible debris. Histological analysis showed particles up to 12 mm in size, consisting of necrotic core, inflammatory cells, cholesterol debris, and old and fresh thrombi. In 8 patients the aspirated particles were too small to allow microscopic diagnosis or debris was absent. CONCLUSIONS: This preliminary report demonstrates the feasibility of using a protection device in native coronary arteries to prevent distal embolisation of particulate matter that is mobilised during percutaneous interventions. To the extent that this material contributes to the mechanisms of distal embolisation, noreflow and infarction, this device may help to reduce such complications. Appropriately designed trials are required to assess the clinical benefit of this system.

Adult↗
PubMed2000

Allelic association between the D10S1423 marker and Alzheimer's disease in a German population.

Recently a full genome survey detected an allelic association between Alzheimer's disease (AD) and the D10S1423 marker on chromosome 10p12-14 (40 cM from the telomere). In this study we examined the D10S1423 marker in an ethnically homogeneous German population of 80 AD patients and two groups of controls, 168 healthy subjects and 149 depressed patients. The 234-bp allele of the D10S1423 marker showed a significant association with AD (P = 0.033). In conclusion, our results support that the D10S1423 marker is associated with an increased AD risk and provides further evidence for an AD susceptibility locus on chromosome 10.

Aged↗
PubMed2000

Decreased frontal lobe ratio of N-acetyl aspartate to choline in familial schizophrenia: a proton magnetic resonance spectroscopy study.

Neuropathological and neuroimaging studies suggest neuronal dysfunction in schizophrenia. N-acetyl aspartate (NAA) is a useful marker of neuronal dysfunction that can be measured with magnetic resonance spectroscopy (MRS). In the present study NAA, choline (Cho), phospho-creatine ((P)Cr), inositol containing compounds and glutamine/glutamate (Glx) were assessed in the left frontal lobe and basal ganglia of subjects with familial schizophrenia, family members with mixed psychiatric diagnoses, unaffected family members, and community controls. Concentrations of metabolites were analyzed and expressed as ratios. NAA/Cho, NAA/(P)Cr and Glx containing compounds showed a negative correlation with age in the frontal lobe. After covarying for age, subjects with schizophrenia had a significant reduction in the left frontal lobe NAA/Cho ratio compared with unaffected family members (P=0.018) as well as with community non-familial (P=0.037) controls. These MRS observations support the hypothesis of a disease-related neuronal deficit in the frontal lobe of schizophrenic patients, and relatively normal basal ganglia.

Adult↗
PubMed2000

Plasma 24S-hydroxycholesterol: a peripheral indicator of neuronal degeneration and potential state marker for Alzheimer's disease.

The conversion of brain cholesterol into 24S-hydroxycholesterol and its subsequent release into the periphery is probably an important step for the maintenance of brain cholesterol homeostasis. Recent findings suggest that plasma 24S-hydroxycholesterol may be elevated in Alzheimer's disease (AD) and vascular dementia at least at some stage of the disease, suggesting increased brain cholesterol turnover during neurodegeneration. We investigated whether plasma 24S-hydroxycholesterol concentrations depend on the severity of AD and on the apolipoprotein E (apoE) genotype. Severity of AD and inheritance of the apoE4 allele were independently associated with reduced plasma 24S-hydroxycholesterol/cholesterol ratios. The results suggest that the decrease of plasma 24S-hydroxycholesterol/cholesterol in severely affected AD patients is a peripheral marker for loss of cholesterol 24S-hydroxylase in the CNS. Inheritance of the apoE4 allele may be associated with increased apoE-mediated transport of brain cholesterol to the periphery or with decreased activity of the 24S-hydroxylase. Longitudinal studies will assess the validity of the ratio plasma 24S-hydroxycholesterol/cholesterol as a state marker for AD.

Aged↗