Biomedical subjects

W Maier

Publications and source records attributed to W Maier.

At least 19 recordsLinked to original sources

PubMed2007

Evaluation of association of SNPs in the TNF alpha gene region with schizophrenia.

The association of the tumor necrosis factor alpha (TNFalpha) -G308A promoter polymorphism with schizophrenia has complemented clinical findings of increased levels of the TNFalpha cytokine in schizophrenic patients, with some support for a functional consequence of the variant. Our previous studies of genetic causes in schizophrenia supported findings of linkage to the major histocompatibility complex (MHC) region where the TNFalpha gene is located as well as association with the -G308A promoter polymorphism. While the common G-allele shows association in our sample, association with the A-allele has been reported by other groups. This suggests linkage disequilibrium (LD) rather than direct involvement in the disorder. In order to define LD of DNA variants with the disorder in this area, we analyzed 36 SNPs in a 165-kb region around this polymorphism. We detected nominally significant associations (P < 0.05) of three markers (including the -G308A promoter polymorphism) and multiple haplotypes with schizophrenia in our sample of 204 families (79 sib-pairs and 125 trios). The association is largely restricted to a 30 kb high LD region/block and should assist in the identification of a schizophrenia susceptibility gene within the block or elsewhere in the MHC.

Family↗

PubMed2007

[Navigated "targeted surgery" for skull base malignomas: additional space for surgical manipulation by neoadjuvant tumor downsizing].

BACKGROUND: Multimodal strategies are required due to the poor prognosis for locally advanced frontal skull base tumors staged as T4. Therefore, a further increase in the degree of invalidity caused by therapy should be avoided, if possible, to preserve the quality of life. As the incidence of these tumors is low, there are no evidence-based, generally accepted therapeutic strategies. METHODS: We evaluated the clinical results of three patients with extended frontal skull base malignomas staged as T4 tumors. The clinical course as well as the surgical technique were analyzed. RESULTS: High dose neoadjuvant therapy for tumor downsizing was performed in all three patients within a multimodal therapy concept. The additional space for surgical manipulation close to the tumor borders, non-traumatically produced by tumor remission, permitted a safely navigated, controlled resection of the tumor under endoscopic or microscopic viewing using an approach associated with reduced trauma as "targeted surgery". CONCLUSIONS: Surgical radicality is limited by the direct vicinity of locally progressive T4 tumors to the frontal brain and other vital structures. A controlled tumor downsizing allows the resection of such tumors using a minimally invasive approach assisted by instrumental navigation leading to less traumatization.

Adult↗

PubMed2007

[Posttraumatic amaurosis after complex frontobasal fracture. Differential diagnosis and therapy].

BACKGROUND: Whether surgical nerve decompression is indicated for the treatment of posttraumatic reduced vision with optic nerve compression in the bony canal has been a subject of controversy for decades. On balance, the recent literature suggests that this procedure is indeed indicated, as a supplement to high-dosed cortisone therapy. The risk of surgery-related side effects is usually rated low in the literature. CASE REPORT: We report on a woman patient in whom craniocerebral trauma involved a fracture of the left optic canal with unilateral loss of vision. In the decompression operation, intraoperative symptoms gave rise to the suspicion of an arteriovenous fistula, which had not been revealed by computer tomography and which was seen as sufficient grounds for discontinuing the procedure. In addition to a carotid artery-sinus cavernosus fistula (CCF Barrow type A), subsequent angiography revealed a dissected aneurysm at the branching of the occluded ophthalmic artery. DISCUSSION AND CONCLUSIONS: In decisions on whether surgical relief of pressure on the optic canal is indicated after trauma-related visual loss, the possibility of secondary lesions near the tip of the orbita and the optic canal must be taken into account. These are not always revealed by computer tomography. The indications should be critically weighed up in each individual case, with additional imaging examinations, such as MR-angiography, CT-angiography, or conventional angiography, performed as needed. The options and indications for imaging are discussed. The procedure can by no means be rated as "minimally invasive", as is postulated by some authors.

Adult↗

PubMed2007

[Sonography aided computer assisted surgery (SACAS) in orbital surgery].

BACKGROUND: The application of computer assisted procedures in orbital surgery is made more difficult by the intraoperative tissue shift in intraorbital structures, since this intraoperative dislocation cannot be imaged in preoperative CT/MR datasets. METHODS: After preoperative recording of CT and/or MR datasets in five patients with orbita affected by frontobasal tumors, we used intraoperative sonography by coupling the ultrasound unit to the navigation system. RESULTS: Registration, referencing and calibration of the ultrasound system proceeded without any difficulties. Intraoperatively, the structures of the anterior and middle thirds of the orbita and their tissue shift could be particularly well evaluated sonographically. CONCLUSION: The use of navigated sonography enables repeated intraoperative re-evaluation of preoperative CT/MR datasets. The fusion of intraoperative sonography with preoperative imaging visualizes the tissue shift and facilitates the identification of anatomical structures and the spatial orientation of the surgeon. This appears to allow both increased operative radicality and greater tissue protection. In our opinion, the intraoperative parallel application of a non-calibrated ultrasound system and an only CT/MRT based navigation system cannot fulfill these requirements because of anatomical complexity.

Adult↗

PubMed2007

[A contribution to the current discussion on anti-dementia drugs in Germany].

In Germany, the role of acetylcholinesterase inhibitors in the treatment of Alzheimer's disease (AD) has become a topic of recent discussion. The present article addresses issues which, in the opinion of the authors, have not received sufficient attention. These include the distinction between statistical and clinical significance, outcome parameters, the duration of clinical trials, variability in treatment response and the definition of treatment responders. The authors argue that these issues need to be considered in an in-depth evaluation of acetylcholinesterase inhibitors in the treatment of AD.

Aged↗

PubMed2007

Impulsiveness in obsessive-compulsive disorder: results from a family study.

OBJECTIVE: Although obsessive-compulsive disorder (OCD) is usually conceptualized as an anxiety disorder some studies suggested it to be a deficit of impulse control. The purpose of this study was to assess impulsiveness in OCD families and compare it to control families. METHOD: Seventy cases and their 139 relatives were compared with 70 controls and their 134 relatives from a German family study on OCD (German Epidemiologic Network for OCD Studies). All subjects were interviewed and diagnosed according DSM-IV criteria and were administered the Barratt Impulsiveness Scale (BIS) and PADUA-Inventory to assess obsessive-compulsive symptoms. RESULTS: OCD subjects had significantly higher scores of cognitive impulsiveness. However, first-degree relatives of OCD cases and of controls had comparable BIS-11 scores. Significant associations of aggressive obsessions and checking with cognitive impulsiveness were found. CONCLUSION: OCD is a severe mental disorder that is characterized by a lack of cognitive inhibition. However, impulsiveness does not represent a familial trait in families of OCD subjects.

Adult↗

PubMed2006

[Peritonsillar abscess: a life threatening disease--diagnostic and therapeutic aspects].

BACKGROUND: Acute tonsillitis is an extremely common infection seen in children and adults. In most cases, the family doctor is initially consulted. Intratonsillar, peritonsillar and retrotonsillar abscesses are frequent complications in the course of tonsillitis. In those cases, oropharyngeal infection may lead to a descending process with consecutive mediastinitis as a life-threatening condition. PATIENTS AND METHODS: We report the case of a 67-year old man who died of a mediastinitis resulting from a peritonsillar abscess. Clinical findings, radiological diagnostics and antibiotic as well as surgical therapy are illustrated. RESULTS: The patient died due to a septic multi-organic failure despite aggressive antibiotic and surgical therapy by a combined enoral and cervical approach with thoracic drainage. DISCUSSION: Peritonsillar abscess is a potentially life-threatening complication of acute tonsillitis. This must be kept in mind and should therefore lead to an adequate and directed management of this pathology. We discuss the stepwise diagnosis and therapy within the framework of scientific literature.

Aged↗

PubMed2006

[Evidence of a novel gene for the LAV-syndrome].

BACKGROUND: Both LAV- (large or enlarged vestibular aqueduct) and Pendred-syndrome are autosomal recessive diseases. In contrast to Pendred-syndrome, LAV-syndrome is characterised only by an enlarged vestibular aqueduct. Pendred-syndrome is a more complex disease. Classically it is characterised by sensorineural hearing loss and enlargement of the thyroid gland. Up to now, only mutations in SLC26A4 gene are known as being responsible for both syndromes. The gene for Pendred-syndrome (SLC26A4) has been localised by linkage analysis of chromosome 7q31. This protein is expressed in the inner ear, thyroid gland, kidney, and placenta. Functional analysis of the gene product (pendrin) in Xenopus laevis oocytes revealed that pendrin acts as an iodide/chloride and chloride/formate exchanger. METHOD: Each of the exons and flanking splice regions of the SLC26A4 gene were analysed by direct sequencing. Haplotype analysis was undertaken with microsatellite markers spanning a 5 Mbp area around the localisation of the SLC26A4 gene. RESULTS: In sequence analysis of 42 patients with bilateral enlargement of the vestibular aqueduct, no mutation could be identified in 30 % of cases. In some of these cases, a linkage to the gene localisation on chromosome 7q31 could not be detected. CONCLUSION: Our results indicate evidence for a second gene involved in the development of LAV-syndrome.

Adolescent↗

PubMed2006

[Craniofacial fibrous dysplasia: scan policy or surgery?].

BACKGROUND: The aetiologic correlations of fibrous dysplasia (FD) are more and more decoded by molecular biology, improved imaging procedures, and the use of computer assisted surgery--thus a review of present diagnostics and therapy methods is evaluated. METHOD: The valid methods of diagnostic and therapy procedures of craniofacial FD were retrospectively analysed in a collective of 9 patients in consideration of literature. The criteria of the decision for diagnosis and surgical procedures were evaluated. RESULTS: According to the literature, diagnosis was ascertained with modern CT and MRI scans. Bone scintigraphy was only used additionally in particular questions. In case of unclear radiological findings histomorphological procedures were used complementarily to distinguish FD from other bone tumors. The aim of surgical intervention was to reduce pain, to restore the function in compression symptoms, to recover original ostia, or to restore the natural geometry of the face. CONCLUSIONS: Current imaging procedures allow differential diagnosis from other benign bone tumors but also from malignancies. The therapy of FD is conservative (wait and scan) or operative in dependence on the localisation, the extension and the clinical manifestations of the disease. In the future molecular biological methods could function as supporting instrument for diagnosis if histomorphological results are not meaningful.

Adult↗

PubMed2006

Rotational tomography of the normal and reconstructed middle ear in temporal bones: an experimental study.

Imaging is an essential diagnostic tool in reconstructive middle ear surgery, especially in pre-operative planning. Due to ongoing improvement of imaging quality and development of new imaging techniques like e.g. rotational tomography (RT) post-operative follow-up and immediate evaluation of surgical results may become more important. The aim of this experimental study was to evaluate RT as a new tool for postoperative determination of middle ear anatomy and implant position in temporal bones. RT was performed in ten temporal bone specimen after insertion of different middle ear prostheses concerning material, shape and length (PORP; TORP; Stapes piston). An implantable hearing device (Symphonix Soundbridge) was also implanted and visualized. For comparison some specimen additionally underwent conventional computed tomography (CT), including the newest technology. Characterization of anatomical structures of the temporal bone using RT was of comparable quality to conventional CT-scans in all investigated specimen while requiring approximately 30% of the CT's irradiation exposure. Unlike CT the RT showed almost no problems due to metallic artefacts of the implanted prostheses. Furthermore RT enabled a 3-dimensional view of the temporal bone and angle determination of inserted prostheses towards the tympanic membrane and/or the malleus handle. Detailed imaging of the prostheses allowed determination of shape, material and localization within the specimen's reconstructed middle ear. The new imaging technique of RT allows precise presentation of anatomical structures and middle ear implants in temporal bones. Following these experimental results it will be our future work to evaluate this method in clinical practise.

Ear, Middle↗

PubMed2006

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin.

Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

Adult↗

PubMed2006

Treatment monitoring and response prediction with proton MR spectroscopy in AD.

In this proton magnetic resonance spectroscopy ((1)H-MRS) study, the authors correlated cognitive improvement after 3 months of treatment with donepezil with changes of N-acetylaspartate (NAA) level and NAA/Creatine (Cr) ratio in the medial temporal and parietal lobe of 17 patients with Alzheimer disease. Treatment response was associated with an increase of NAA and NAA/Cr in the parietal lobe. Low baseline NAA/Cr in the parietal lobe predicted positive treatment outcome.

Aged↗

PubMed2006

Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase IIalpha gene (PIP5K2A) with schizophrenia.

Linkage studies in schizophrenia have identified a candidate region on chromosome 10p14-11 as reported for several independent samples. We investigated association of DNA sequence variants in a plausible candidate gene located in this region, the gene for phosphatidylinositol-4-phosphate 5-kinase IIalpha (PIP5K2A), in a sample of 65 sib-pair families for which linkage had been reported. Evidence for association was obtained for 15 polymorphisms spanning 73.6 kb in the genomic region of the gene between intron 4 and the 3' untranslated region, a region with high degree of linkage disequilibrium. Single nucleotide polymorphism (SNP) rs10828317 located in exon 7 and causing a non-synonymous amino-acid exchange (asparagine/serine) produced a P-value of 0.001 (experiment-wide significance level 0.00275) for over-transmission of the major allele coding for serine, analysed by transmission disequilibrium test using FAMHAP. Association of this SNP with schizophrenia has been also described in a sample of 273 Dutch schizophrenic patients and 580 controls (P=0.0004). PIP5K2A is involved in the biosynthesis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), one of the key metabolic crossroads in phosphoinositide signalling. PI(4,5)P2 plays a role in membrane transduction of neurotransmitter signals as well as in intracellular signalling, pathways that may be impaired in schizophrenia.

Base Sequence↗

PubMed2006

Influence of lysosomal acid lipase polymorphisms on chromosome 10 on the risk of Alzheimer's disease and cholesterol metabolism.

Linkage analyses have identified a possible hot spot for a late-onset Alzheimer's disease (LOAD) risk gene on chromosome 10q21-22 and 10q25. It was also shown that cholesterol metabolism is involved in the pathogenic mechanisms of AD. The gene of lysosomal acid lipase (LIPA) is located next to the putative hot spot on chromosome 10. Its protein is involved in cholesterol metabolism and responsible for catalysing the hydrolysis of cholesteryl esters and triglycerides inside the lysosome. Previous publications reported controversial results on the role of LIPA polymorphisms on the risk of LOAD. We investigated two LIPA polymorphisms (rs1051338 and rs2297472) for their putative effect on the risk of LOAD in a homogenous sample of German origin. Genotypes of the investigated polymorphisms in AD patients and controls were compared. Also the effect of the LIPA gene polymorphisms on plasma cholesterol levels and 24S-hydroxycholesterol/cholesterol ratios on AD patients were investigated. None of the observed polymorphisms showed a significant influence on the risk of AD. We found that LIPA exon 2 polymorphism (rs1051338) influenced plasma 24S-hydroxycholesterol/cholesterol ratios in AD patients where carriers of the C/C allele presented with higher ratios than heterozygote carriers of the LIPA allele. Even though the biological function and gene location of LIPA on chromosome 10 suggest that LIPA might be a candidate for an AD risk gene, our results revealed that polymorphisms in LIPA did not influence the risk of AD in our study.

Aged↗

PubMed2006

Prognostic relevance of anamnestic and diagnostic parameters in low-frequency hearing impairment.

Low-frequency hearing impairment (LFHI) is mainly attributed to endolymphatic hydrops and has a great variety of possible outcomes. At present, no conservative therapeutic regimen has proven to be 'gold-standard', and information about the prognostic indicators of LFHI is scarce. In a retrospective investigation, we evaluated the records of 90 patients who had been treated with infusions improving blood perfusion. In patients lacking complete remission, dehydration infusion therapy was added. We also undertook audiometric follow up. We calculated the outcomes after infusion therapy, dehydration therapy and after long-time hearing follow up, and we determined the prognostic relevance of several parameters of anamnesis and clinical examination to outcomes, for both therapeutic interventions and long-time hearing. The prognosis of LFHI was significantly correlated to certain anamnestic and clinical parameters; a short duration of the disease, lack of vertigo and female gender implied a better outcome. The pretherapeutic hearing threshold was an important prognostic factor; the outcome was significantly worse in patients with distinct hearing impairment in low or high frequencies, compared with that in patients with little hearing loss. Whereas vertigo was a negative prognostic factor, the results of quantitative vestibular testing were irrelevant to the outcome. The glycerol test failed to predict the effectiveness of dehydration therapy and lacked any value in predicting prognosis. These results allow the clinician to focus the anamnesis and diagnostic examination on prognostically relevant parameters, thus enabling a better estimation of the long-term disease course and improved counselling of patients. Furthermore, these results help to distinguish valuable from irrelevant diagnostic procedures.

Acetazolamide↗

PubMed2006

Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14.

Preliminary studies suggested that age at onset (AAO) may help to define homogeneous bipolar affective disorder (BPAD) subtypes. This candidate symptom approach might be useful to identify vulnerability genes. Thus, the probability of detecting major disease-causing genes might be increased by focusing on families with early-onset BPAD type I probands. This study was conducted as part of the European Collaborative Study of Early Onset BPAD (France, Germany, Ireland, Scotland, Switzerland, England, Slovenia). We performed a genome-wide search with 384 microsatellite markers using non-parametric linkage analysis in 87 sib-pairs ascertained through an early-onset BPAD type I proband (AAO of 21 years or below). Non-parametric multipoint analysis suggested eight regions of linkage with P-values<0.01 (2p21, 2q14.3, 3p14, 5q33, 7q36, 10q23, 16q23 and 20p12). The 3p14 region showed the most significant linkage (genome-wide P-value estimated over 10 000 simulated replicates of 0.015 [0.01-0.02]). After genome-wide search analysis, we performed additional linkage analyses with increased marker density using markers in four regions suggestive for linkage and having an information contents lower than 75% (3p14, 10q23, 16q23 and 20p12). For these regions, the information content improved by about 10%. In chromosome 3, the non-parametric linkage score increased from 3.51 to 3.83. This study is the first to use early-onset bipolar type I probands in an attempt to increase sample homogeneity. These preliminary findings require confirmation in independent panels of families.

Adolescent↗

PubMed2006

[Cochlear protection and surgical precision in stapedotomy with Er:YAG laser].

BACKGROUND: Using laser in stapedotomy has attracted a lot of attention since the nineties. It aims at minimizing complications due to hand-operated equipment, especially inner ear lesions, and achieving higher precision. We analyzed the clinical effect of Er:YAG laser with the question whether the postulated cochlea protection and foot plate perforation, optimized for better sound conduction, are achieved, compared to conventional stapedotomy. PATIENTS AND METHODS: We evaluated retrospectively audiometrical data including pre- and postoperative bone and air conduction thresholds of 114 consecutive patients, on whom we had performed stapedotomy and had inserted platinum-teflon prostheses. The intervention was done conventionally in 72 cases and in 42 cases with Er:YAG laser. RESULTS: In the lower and middle frequencies, laser technique resulted in a more pronounced improvement of bone conduction thresholds compared to conventional stapedotomy. The improvement of air conduction was more distinct in ears after laser surgery; also, the difference between air and bone conduction was reduced at a higher degree. CONCLUSION: Er:YAG laser in stapedotomy is coupled with cochlea protection, as demonstrated under clinical conditions, and allows higher hearing benefit of air conduction compared to conventional stapedotomy. Our results emphasize the impact of innovative laser technique on stapedotomy.

Adult↗

PubMed2006

Transmission disequilibrium and haplotype analyses of the G72/G30 locus: suggestive linkage to schizophrenia in Palestinian Arabs living in the North of Israel.

Association of the G72/G30 locus with schizophrenia was recently reported in French Canadian, Russian, and Ashkenazi populations using case-control studies. In the present study we hypothesize the existence of a G72/G30 risk allele over-transmitted to affected sibs in Palestinian Arab families. A total of 223 Palestinian Arab families that included an affected offspring and parents were genotyped with 11 SNPs encompassing the G72/G30 genes. The families were recruited from three regions of Israel: 56 from the North (Afula), 136 from the central hill region (Bethlehem, Palestinian Authority), and 31 from the South (Beersheva). Individual SNP analyses disclosed a risk allele in SNP rs3916970 by both haplotype relative risk (HRR: chi(2) = 5.59, P = 0.018) and transmission disequilibrium test (TDT: chi(2) = 6.03, P = 0.014) in the Afula families. Follow-up multilocus analysis using family-based association tests (FBAT: z = 2.197, P = 0.028) exposed the adjacent haplotype. SNP rs3916970 is located about 8 kb from the linkage disequilibrium block that was reported to be associated with schizophrenia in Ashkenazi Jews. Excess of similar haplotypes of this region was observed in the Palestinian Arabs and the Ashkenazi patients. These data suggest a common risk factor for schizophrenia susceptibility in the G72/G30 locus among Ashkenazi Jews and Palestinian Arabs. The results strengthen previous reports on the role of this locus in the etiology of schizophrenia.

Alleles↗