Biomedical subjects

W Maier

Publications and source records attributed to W Maier.

At least 199 records · Page 11Linked to original sources

PubMed1999

Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer's disease.

The beta amyloid peptide derives from its precursor protein via proteolytic cleavage of yet unidentified proteases (beta- and gamma-secretases). Cathepsin D is an intracellular protease with in-vitro beta-secretase-like features. An exonic polymorphism of the cathepsin D gene (alanine to valine transition at position 224, exon 2) has been associated with altered enzyme function. We tested the hypothesis that this polymorphism is associated with an increased risk for Alzheimer's disease in 102 demented patients, 191 healthy subjects, and 160 depressed patients. There was a highly significant overrepresentation of the cathepsin D*T allele in demented patients (14.2%) compared to non-demented controls (6.7%, P = 0.0012). Carriers of the cathepsin D*T allele had a 2.4-fold increased risk for developing AD than non-carriers. Carriers of the apolipoprotein E epsilon 4 allele had a 4.1 -fold increased risk than non-carriers. The odds ratio for subjects with the apolipoprotein E epsilon 4 and the cathepsin D*T allele was 5.9. Our data suggest that the cathepsin D genotype is strongly associated with the risk for Alzheimer's disease.

Aged↗

PubMed1999

DAT1 gene polymorphism in alcoholism: a family-based association study.

BACKGROUND: The present study tests the hypothesis that the 9-repeat allele of the dopamine transporter gene (DAT1; SLC6A3) is more frequent in alcohol-dependent probands--and in particular those with severe withdrawal symptoms (seizures and/or delirium)--compared to nonalcoholics. METHODS: To avoid stratification effects, the family-based association approach of Falk and Rubinstein was used in our sample of 87 alcohol-dependent probands and their biological parents. RESULTS: By applying a family-based association approach, we were not able to detect significant association between allele 9 at DAT1 (SLC6A3) and alcoholism as well as between patients with or without severe withdrawal symptoms. CONCLUSIONS: Based on our data, the impact of the 9-repeat allele of the dopamine transporter gene in alcoholism and the severity of alcohol withdrawal symptoms is putatively not substantial.

Alcoholism↗

PubMed1999

A genetic variation of the inflammatory cytokine interleukin-6 delays the initial onset and reduces the risk for sporadic Alzheimer's disease.

Local inflammatory processes surrounding the amyloid plaques contribute to the progression and acceleration of the Alzheimer's disease (AD)-related neurodegeneration. Interleukin-6 (IL-6) is an inflammatory cytokine with possible involvement in the local immune response occurring in the central nervous system of AD patients. We tested the hypothesis as to whether a genetic polymorphism of the IL-6 gene (IL-6) modifies the age at onset and risk for sporadic AD. Our results support an association of the C allele of the IL-6 genotype with a delayed initial onset and reduced disease risk and indicate that genetically determined alterations of the immune response may modify the course of AD.

Age of Onset↗

PubMed1999

Essential functions of the human self model are implemented in the prefrontal cortex.

The human self model comprises essential features such as the experiences of ownership, of body-centered spatial perspectivity, and of a long-term unity of beliefs and attitudes. In the pathophysiology of schizophrenia, it is suggested that clinical subsyndromes like cognitive disorganization and derealization syndromes reflect disorders of this self model. These features are neurobiologically instantiated as an episodically active complex neural activation pattern and can be mapped to the brain, given adequate operationalizations of self model features. In its unique capability of integrating external and internal data, the prefrontal cortex (PFC) appears to be an essential component of the neuronal implementation of the self model. With close connections to other unimodal association cortices and to the limbic system, the PFC provides an internally represented world model and internal milieu data of the organism, both serving world orientation. In the pathophysiology of schizophrenia, it is the dysfunction of the PFC that is suggested to be the neural correlate for the different clinical schizophrenic subsyndromes. The pathophysiological study of psychiatric disorders may contribute to the theoretical debate on the neuronal basis of the self model.

Body Image↗

PubMed1999

Family and genetic studies on the relationship of schizophrenia to affective disorders.

Schizophrenia is a genetically influenced disease with a broad and heterogeneous phenotype transmitted in families. Of particular interest is the familial-genetic relationship between schizophrenia and affective disorders. Taking advantage of refined epidemiological methods, the dichotomy between both groups of disorders is not less consistently found than expected. Recently, linkage studies identified multiple candidate regions for susceptibility genes for each of both disorders. Several of these candidate regions for schizophrenia are overlapping with candidate regions for bipolar disorder. Thus, the hypothesis of an etiological dichotomy of schizophrenia and affective disorders faces a new challenge.

Chromosome Aberrations↗

PubMed1999

[Genetics of schizophrenic disorders. New concepts and findings].

Schizophrenia is a genetic complex disease as it does not follow monogenic transmission while non-familial environmental factors have a strong additional impact. A heterogeneous, continuous phenotype is transmitted in families which can now be more precisely characterized. Genes coding for proteins with presumed pathophysiological relevance are apparently not playing a major causal role. However, in the last three years several (currently seven) candidate regions have been identified in a replicable manner by linkage studies. These regions are likely to host susceptibility genes for schizophrenia, but none of them has been identified up to now. Given these findings, polygenic transmission has now become very likely. The candidate regions are currently being narrowed down by various promising techniques.

Biomarkers↗

PubMed1999

[Recurrent, primary multifocal malignant melanoma of the mucous membrane of the upper respiratory tract. Peculiarities of the in-situ components].

We report on a patient who at 61 years of age presented with two nodular melanomas in the right nasal cavity. These tumors were limited to the mucosal membrane and were accompanied by a large amount of atypical hyperplasia of the melanocytes within the glandular and surface epithelium of various other samples of the mucous membrane, a finding also verified immunohistochemically. These tumors were treated surgically. In the clinical course, after a prolonged tumor-free interval, a malignant melanoma of the contralateral nasal cavity occurred, in addition to recurrences in the area of the primary tumor. It seems likely that the large, diffuse proliferation of atypical melanocytes observed could have been the starting point of both the tumor recurrences and the second primary. Thus, in a histologically proven melanoma in the mucous membranes of the upper respiratory system, a more intense preoperative histological diagnostic procedure, in given cases with the assistance of immunohistochemical methods, could be useful to demonstrate intraepithelial atypical melanocytes. It is possible that by doing this the present poor prognosis for mucosal melanomas of the upper respiratory tract might be improved.

Female↗

PubMed1999

Gender differences in the prevalence of depression: a survey in primary care.

Epidemiological surveys demonstrate that unipolar depression is more common in females than in males. Gender-specific cultural and social factors may contribute to the female preponderance. This study explores this possibility in a cross-cultural sample of general-practice patients systematically recruited in the WHO study "Psychological Problems in Primary Care" conducted in 14 countries with identical sampling and assessment strategies. Although absolute prevalence rates are broadly varying between centers proposing that the gender ratio is nearly constant with 1:2. The cultural context does not contribute substantially to the female preponderance. This study lends some support to previous observations that the magnitude of female preponderance is associated with the number of symptoms associated with depression requested for caseness and inversely related to the degree of social impairment. Matching social role variables (marital status, children, occupational status) between females and males reduces the female excess by about 50% across all centers. Therefore, we conclude that social factors are inducing part of the preponderance of females among depressed cases.

Adult↗

PubMed1999

Differential memory span--abnormal lateralization pattern in schizophrenic patients and their siblings?

The recurring digit span test is hypothesized to assess consolidation memory and hypothetically addresses neuropsychological left-temporohippocampal functioning, an area of the brain which is presumed to play a crucial role in schizophrenia. The present study applied the recurring digit span memory test and the recurring block span memory test (assumed to be an indicator of right-temporohippocampal functioning) to 106 acute schizophrenic patients (DSM-III-R), 49 siblings of these patients without DSM-III-R lifetime diagnoses as well as 53 non-related control subjects without DSM-III-R lifetime diagnoses. Results of our investigation indicate that schizophrenic patients differ from control subjects regarding recurring digit span in a reduced number of correct reproductions of recurring trials. Since performance of schizophrenic patients was only non-significantly different from control subjects regarding recurring block span memory, our findings point to a task-specific memory impairment in schizophrenia and argue against a generalized deficit in this disease. Furthermore, individuals at risk for schizophrenia also differed from control subjects concerning the recurring digit span memory test but not with regard to the recurring block span test. Therefore we conclude that the reduced cumulative learning curve of verbal material (reduced number of correct reproduction of recurring digit trials) in schizophrenic patients and their healthy siblings might represent a marker for the liability to schizophrenia and parallels neuroimaging findings concerning left-sided temporohippocampal abnormalities in this disease, which presumably play a key role in the etiology of schizophrenia.

Adult↗

PubMed1999

Endoscopic ultrasound-guided brachytherapy of head and neck tumours. A new procedure for controlled application.

Brachytherapy is an established procedure in primary and in recurrent cancer. We perform afterloading brachytherapy during general anaesthesia. The target organ is punctured with hollow needles which are loaded with 192iridium via remote control. The depth and number of needles depend on tumour extension. In the interdisciplinary approach of our departments, this method has been improved and supplied by B-scan ultrasound control. Needles are positioned under continuous ultrasonographic guidance, and adjacent structures (e.g. the carotid artery) are localized ultrasonographically. Thus violation of the large vessels is avoided and the exact position of the needles within the tumour is improved. In this paper, we report results on 22 patients suffering from recurrent carcinoma of the head and neck following surgery and curative radiation, and 17 patients with first onset of cancer. We did not observe any severe complications such as haemorrhage, osteomyelitis, or dyspnoea. The only side-effect was temporary oedema, sometimes associated with a short-term increase of pain. No systemic side-effects occurred. The method is described and results from both patient groups are reported in detail. We conclude from our data that ultrasonographically-controlled endoscopic brachytherapy is a valuable procedure in locally-advanced primary, and in recurrent head and neck cancer.

Aged↗

PubMed1999

Paraganglioma as a systemic syndrome: pitfalls and strategies.

Tumours of the neuroendocrine system in the head and neck region are mostly paragangliomas of the glomus tympanicum or jugulare, or of the carotid body. The majority of these tumours are benign, and the coexistence of multiple paragangliomas seems to be rare. Pre-operative embolization and surgery are regarded as primary therapy for these tumours. The treatment regimen in any patient depends on age, general health, hearing status and the function of the lower cranial nerves. Several presentations are possible in which paragangliomas occur as systemic disease. 1. Paragangliomas may occur bilaterally, or, in rare cases, in multiple areas. Pre-operative bilateral angiography is of utmost importance. In case of multicentricity, it might be necessary to proceed without, or just with, unilateral surgery for preservation of adjacent structures. In surgery of jugular vein paraganglioma, we usually perform a modified transmastoidal and transcervical approach with preservation of middle-ear structures and the ossicles. As an alternative or supplement to surgery, radiotherapy or definitive embolization may be used in the treatment of paragangliomas. 2. Paragangliomas may occur as multiple endocrine neoplasia (MEN) syndrome combined with medullary thyroid gland carcinoma, and, facultatively, pheochromocytoma. In these cases, endocrinological examination and magnetic resonance imaging (MRI) of the adrenal region, the thorax and the neck are required for an adequate therapeutic strategy. As MEN may be inherited, family history should be evaluated. 3. Paragangliomas can became malignant and metastasize. Thus, cervical lymph node metastases or distant metastases may occur. We recommend the removal of all ipsilateral lymph nodes and their histological examination.

Adult↗

PubMed1999

The impact of dementia on the detection of depression in elderly subjects from the general population.

BACKGROUND: The performance of the CES-D in a sample of elderly community residents was assessed. The influence of dementia on test performance and the necessity for the use of four factor scores instead of a single summary score of the CES-D were studied. METHOD: Two hundred and eighty-seven subjects out of the general population aged 60-99 years were personally interviewed with standardized diagnostic tools and completed the CES-D. Best-estimate diagnoses served as 'gold standards' for receiver operating characteristics (ROC) analysis. RESULTS: The CES-D discriminated well between depressive and non-depressive subjects. Exclusion of demented subjects from the sample did not markedly increase test performance. Current depressive illness and dementia led to high scores on the CES-D. Unlike the factors 'depressive affect', 'somatic/vegetative complaints', and 'interpersonal relations', the factor' positive affect' of the CES-D discriminated well between demented and non-demented participants. CONCLUSIONS: The CES-D is a valid instrument for screening for depression in a community sample of elderly subjects. Its use can be recommended even if the presence of dementia is likely. The use of factor scores of the CES-D does not substantially contribute to an improvement of overall test performance, but, nevertheless, allows a more detailed insight and better interpretation of test results.

Aged↗

PubMed1999

Determining working memory from ERP topography.

Event-related potentials were recorded during a delayed matching-to-sample design from 17 volunteers (5 f) using high-resolution (65 channels) EEG-recordings. In the two-stimulus paradigm, the 500-ms stimulus S1 comprised a visual pattern of two diamonds differing in size, angular rotation and location; in the delay period, Working Memory (WM) load was varied in the following way: a stimulus-free interval of 1 s was followed by a 6-s presentation either of a pattern identical to the S1 (low WM load) or of a pattern differing from S1 (high WM load). The 500-ms stimulus S2 comprised one diamond; the subject's task was to indicate by left- or right-hand (respectively) button press, whether the S2 matched the (a) left- or (b) right-positioned S1-diamond, or (c) did not match at all (NoGo). The topographical distribution of activity in the time intervals (a) following S1-offset, (b) during the WM manipulation interval and (c) prior to S2 were evaluated in the signal (scalp potential) and source (Minimum Norm) space. Following S1-offset the ERP pattern was characterised by negativity over posterior areas, slightly more so over the right hemisphere. In the subsequent 6-s interval high WM load elicited a larger negative slow ERP than low WM load, the negativity increase due to high WM load being larger over frontal than central areas. Source modelling indicated activity in anterior areas under high, and posterior activity under low WM load. Asymmetry of activity, although indicating a shift to left-hemispheric activity under high compared to low WM load, varied considerably between subjects. Results suggest that high-resolution ERP recordings allow to examine cortical activity during WM challenge.

Adolescent↗

PubMed1999

Evaluation of linkage of bipolar affective disorder to chromosome 18 in a sample of 57 German families.

Previously reported linkage of bipolar affective disorder to DNA markers on chromosome 18 was reexamined in a large sample of German bipolar families. Twenty-three short tandem repeat markers were investigated in 57 families containing 103 individuals with bipolar I disorder (BPI), 26 with bipolar II disorder (BPII), nine with schizoaffective disorder of the bipolar type (SA/BP), and 38 individuals with recurrent unipolar depression (UPR). Evidence for linkage was tested with parametric and non-parametric methods under two definitions of the affected phenotype. Analysis of all 57 families revealed no robust evidence for linkage. Following previous reports we performed separate analyses after subdividing the families with respect to the sex of the transmitting parent. Fourteen families were classified as paternal and 12 families as maternal. In 31 families the parental lineage of transmission of the disease could not be determined ('either' families). Evidence for linkage was obtained for chromosomal region 18p11.2 in the paternal families and for 18q22-23 in the 'either' families. The findings on 18p11.2 and 18q22-23 support prior evidence for susceptibility loci in these regions. The parent-of-origin effect on 18p11.2 is confirmed in our sample. The delineation of characteristics of 'either' families requires further study.

Bipolar Disorder↗

PubMed1999

Association between hSKCa3 and schizophrenia not confirmed by transmission disequilibrium test in 193 offspring/parents trios.

A possible association between the small conductance calcium-regulated potassium channel gene, hSKCa3, and schizophrenia has recently been described by Chandy et al using a case-control design with patients with schizophrenia (n=141) and matched controls (n = 158). The gene may be considered as an excellent candidate gene for psychiatric disorders, since it plays a role in modulating neuronal firing patterns by regulating the slow component of after hyperpolarisation. In addition, the gene contains a highly polymorphic trinucleotide sequence (CAG) within exon 1, which encodes a polyglutamine stretch. The possible contribution of unstable trinucleotide repeats to the development of psychiatric disorders has previously been discussed. Chandy et al reported an over-representation of alleles with higher repeat number in schizophrenics as compared to controls (P = 0.0035). In an attempt to replicate these findings, we have performed a family-based study with 193 offspring/parent combinations using a sample of 49 multiplex families (two or more affected siblings with parents) and a second sample of 83 simplex families (one affected offspring with parents). No evidence for the association of longer repeats with schizophrenia was obtained when each sample was tested separately or when both samples were combined and tested for transmission disequilibrium.

Female↗

PubMed1999

Audit and quality control in angioplasty in Europe: procedural results of the AQUA Study 1997: assessment of 250 randomly selected coronary interventions performed in 25 centres of five European countries. AQUA Study Group, Nucleus Clinical Issues, Working Group Coronary Circulation, of the European Society of Cardiology.

AIMS: Percutaneous transluminal coronary angioplasty (PTCA) has become the most widely used major intervention in western medicine. However, there is disparate use of this technique among different European countries and the U.S.A. In an attempt at quality assurance, the working group Coronary Circulation of the European Society of Cardiology has carried out a study on appropriateness, necessity, and performance of PTCA in Europe. The present paper reports on the procedural results of this survey. METHODS: In a multicentre case-control study in Europe, 750 patients (544 men, 206 women) with documented vascular disease of the From the countries participating in the European Registry of Coronary Intervention, the three countries with the highest absolute PTCA volume (Germany, France, and the United Kingdom) and two randomly selected countries (Belgium and Italy) were chosen for investigation. In these countries, five centres were selected at random according to the following criteria: one centre with >1000, three centres with 300-1000, and one centre with <300 procedures per year. In each of these, 10 cases from the first half of 1997 were randomly identified and all pertinent documentation was collected. RESULTS: In 250 cases, 325 stenoses were addressed as target lesions. Single vessel disease was present in 41%. History included stable angina in 49%, unstable angina in 32%, atypical chest pain in 6%, no anginal pain in 12%, and acute/subacute myocardial infarction in 13%. The percentage of patients with either positive stress test and/or unstable angina, acute/subacute infarction, previous infarction (within 6 months) or coronary revascularization amounted to 98%. Single vessel intervention accounted for 90%. In 41% balloon-only angioplasty was performed and in 54% at least one stent was implanted with considerable variation among countries. The use of other new devices amounted to only 3%. In 92%, the operators documented a successful procedure. Major complications (myocardial infarction, emergency bypass surgery, or death) were found in 4.8%. CONCLUSIONS: Based on scrutinized hospital and operator data, the present study revealed a satisfactorily high percentage of justifiable indications, an adequate procedural success rate, and an acceptably low complication rate. Further analysis by an expert panel will address appropriateness, necessity, and procedural performance of the individual cases.

Angioplasty, Balloon, Coronary↗

PubMed1999

[Value of B-image ultrasound in patients with carcinomas of the upper aerodigestive tract and N0 lymph node stage].

BACKGROUND: The wait-and-see policy in patients with a N0 neck stage is not common. PATIENTS AND METHOD: One hundred twenty-one patients with a pT1 or pT2 carcinoma of the upper aerodigestive tract and a N0 neck stage in ultrasound studies underwent transoral laser microsurgery without neck dissection or radiation therapy. In these patients the probability of survival and local or regionals recurrence were analyzed in a follow-up period of 18 to 36 months. RESULTS: Thirty patients in whom cervical lymph nodes were detected in ultrasound studies, underwent a curative neck dissection procedure. In 8 of these 30 patients, lymph node metastases were histologically demonstrated, and 6 patients showed a local recurrence. The probability of survival was 1.0 and the probability of being free of local or regional recurrence was between 0.95 and 0.6 depending on the tumor location. CONCLUSIONS: A wait-and-see policy will not necessarily alter the prognosis, which depends on the location of the tumor. Ultrasound follow-up studies should be performed at regular intervals.

Adult↗

PubMed1999

Competence to give informed consent to clinical studies. Statement by the taskforce on "ethical and legal questions" of the Association for Neuropsychopharmacology and Pharmacopsychiatry ("Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie [AGNP]").

Over the last 50 years, patient autonomy has become an increasingly important part of the principles of medical ethics, or rather of the ethics of the doctor-patient relationship. While the principle of charity and the associated paternalism became less important, the patient's active consent became more and more relevant (Sass, 1989; Bayer, 1998; Nedopil, 1998). This development was inevitably also accompanied by a demand for more detailed information prior to medical interventions (Appelbaum and Grisso, 1988; Weisstub, 1990; Kreussler, 1997; Ulsenheimer, 1995; Laufs, 1997; Sommer, 1997) and for complete information on medical procedures subsequent to interventions (e. g. Bender, 1997). Determination of a person's competence to give informed consent is a central problem in the assessment of his expression of consent to a medical intervention. The capacity to adequately express consent can be impaired at certain stages of life and during some illnesses. Patients in borderline situations, children, mentally ill patients and old people with dementia may either be limited in their capacity to give informed consent, or be completely unable to do so. This results in special ethical problems when such groups are included in research projects.

Clinical Trials as Topic↗