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Biomedical subjects

W Maier

Publications and source records attributed to W Maier.

At least 73 records · Page 4Linked to original sources

Altered levels of plasma 24S- and 27-hydroxycholesterol in demented patients.

Alterations in brain cholesterol metabolism and reduced 24S-hydroxycholesterol plasma levels have been described in Alzheimer's disease (AD) and vascular dementia (VD). We hypothesize that changes in peripheral cholesterol metabolism, such as alterations in the plasma levels of 27-hydroxycholesterol, might also be involved. Plasma levels of 24S-hydroxycholesterol and 27-hydroxycholesterol in patients suffering from dementing disorders such as AD, VD, and mild cognitive impairment (MCI) were compared to those in age- and cholesterol matched non-demented and depressed subjects. Cholesterol corrected concentrations of plasma 24S-hydroxycholesterol and 27-hydroxycholesterol were significantly reduced in patients with dementing disorders compared to non-demented subjects and depressed patients. A strong positive correlation between plasma 24S-hydroxycholesterol and 27-hydroxycholesterol levels was observed. The ratios of plasma 24S-hydroxycholesterol to 27-hydroxycholesterol were higher in patients with dementing disorders compared to non-demented subjects. Our results support the observation, that cholesterol metabolism is altered in dementing disorders, indicated by different plasma concentrations of brain specific and peripherally produced oxysterols.

Aged↗

The efficacy of inhibitors involved in spermidine metabolism in Plasmodium falciparum, Anopheles stephensi and Trypanosoma evansi.

In the present study, we have tested the effect of different polyamine inhibitors of the spermidine metabolizing enzymes deoxyhypusine synthase and homospermidine synthase in different chloroquine resistant Plasmodium falciparum strains, in the mosquito Anopheles stephensi (Diptera: Culicidae) and in a Trypanosoma evansi clone I from strain STIB 806 K China. Recent experiments have shown that agmatine is a growth inhibitor of the malaria parasite P. falciparum (Kaiser et al. 2001) in vitro. A comparison of agmatine efficacy with the new antimalarials artemisinin, triclosan and conventional chloroquine showed similar or even better results on the basis of growth inhibition and the reduction of developmental forms. However, no effect of triclosan or agmatine was observed at the ribonucleic acid level. In a second set of experiments, we tested the effect of 1,7-diaminoheptane and agmatine on oocyst formation in A. stephensi after infection with Plasmodium yoelii. Agmatine had an antisporozoite effect since 1,000 microM led to a 59.5% inhibition of oocysts. A much weaker inhibitor of oocyst formation was 1,7-diaminoheptane. The most effective in in vitro inhibition of T. evansi was dicyclohexylamine, an inhibitor of spermidine biosynthesis with an IC(50 ) value of 47.44 microM and the deoxyhypusine inhibitor 1,7-diaminoheptane with an IC(50) value of 47.80 microM. However, both drugs were ineffective in in vivo experiments in a Trypanosoma mouse model. Two different spermidine analogues, 1,8-diaminooctane and 1,3-diaminopropane with IC(50) values of 171 microM and 181.37 microM, respectively, were moderate inhibitors in vitro and ineffective in vivo.

Animals↗

[Genetics of depression. Current knowledge and perspectives].

Depression is a common disorder (lifetime prevalence nearly 20% in industrialized countries) that presents in two etiologically different forms (unipolar depression, bipolar disorder). Both forms are subject to a genetic influence, which is stronger in bipolar disorder. Unipolar depression is also strongly influenced by nongenetic environmental factors (e. g., traumas, socialization, critical life events). There is strong evidence for a gene-- environmental interaction in unipolar depression. The search for genes was recently very successful in bipolar disorder. There is currently no evidence for disposition genes with strong effects. The prediction of response to selective serotonin-reuptake inhibitors (SSRI) by genetic markers presents currently the best confirmed molecular-genetic findings for unipolar depression. Complicating factors are gene--environmental interaction, only small to modest effects of disposition genes, and putative epigenetic mechanisms.

Adolescent↗

[Paragangliomas of the head and neck. Part 2: Therapy and follow-up].

Paragangliomas of the head and neck are preferably treated surgically. Planning the surgical approach for temporal bone paragangliomas is performed according to the Fisch classification. Small temporal paragangliomas can be removed in a transtympanic or transmastoidal procedure. Locally advanced paragangliomas of the head and neck have to be embolized presurgically. An occlusion test is also recommended to check the possibility of a resection of the internal carotid artery. Type C and D temporal bone paragangliomas can be removed by different infratemporal approaches. Alternatively, some type C(1,2 )and De,i(1,2) temporal bone paragangliomas can be removed via variations of the juxtacondylar approach. Glomus caroticum tumors are resected transcervically. In cases of contraindications for surgery or in palliative situations radiotherapy is recommended.

Carotid Arteries↗

[Paragangliomas in the head-/neck region. I: Classification and diagnosis].

Paragangliomas of the head and neck occur sporadically or are hereditary. The hereditary phenotype characteristically occurs between the 2nd and 3rd decade of life; the sporadic phenotype beyond the 4th decade. The hereditary phenotype "paraganglioma syndrome type 1" frequently shows multilocular tumor manifestations and rarely cases of maltransformation. Therefore, paragangliomas should be considered a systemic disease. For diagnosis, an interdisciplinary, step by step procedure is mandatory comprising genetic screening, whole body medical check-up including catecholamine metabolism, and optionally an 18F-Dopa-PET and localised imaging procedures.

Diagnosis, Differential↗

[The anterosigmoidal approach. A function-preserving surgical method for petroclival tumors].

BACKGROUND AND OBJECTIVE: The antero- or persigmoid approach preserves all functional structures of the petrous bone and, therefore, is an alternative to the classic laterobasal approaches for exploring the petroclival region. As high morbidity is assumed and it is a time consuming procedure, this approach is not well known. METHODS AND PATIENTS: Initially, a cadaver study using computer assisted surgery was used to determine the surgical workflow before we optimized our surgical procedures. RESULTS: In a series of 7 patients with benign tumors growing from the petrous apex to the petroclival region, we were able to resect all tumors completely via the anterosigmoidal surgical corridor using computer assisted surgery. CONCLUSIONS: The navigation-guided anterosigmoidal approach is an excellent method, allowing a good overview of the petroclival region. In patients suffering from complex petroclival tumors, it offers a real chance to achieve complete microsurgical tumor resection without functional defects by an interdisciplinary neuro-oto-surgical session.

Adolescent↗

[Neurophysiologic intraoperative monitoring to preserve cranial nerve function in base of skull surgery].

BACKGROUND: Neurophysiologic intraoperative monitoring (NIM) has gone through a renaissance since the advent of computer technology. Currently, both motor and sensory cranial nerves, including the IInd and VIIIth cranial nerves, can be intraoperatively controlled by means of small and mobile systems. PATIENTS AND METHODS: In order to estimate the value of NIM using the new generation of computer systems, we analyzed the records of 379 patients who underwent skull base surgery since 1996. These comprised NIM of the IInd, VIIth, VIIIth cranial nerves in most cases and of the IXth, Xth, XIth, and XIIth cranial nerves in selected cases. RESULTS: Whereas 72% of these cases demonstrated changes in the recorded intraoperative NIM signals, only 29% of them gave evidence of either clinical or electrophysiological neural function alterations during the postoperative follow-up. CONCLUSIONS: NIM is the only available system capable of providing the surgeon with instant intraoperative neural status-related feedback.

Computer Systems↗

[Endophenotype--a new concept for biological characterization of psychiatric disorders].

In the field of psychiatric genetics, the concept of endophenotypes is presently receiving high popularity. Current difficulties in the search for susceptibility genes of complex diseases have been attributed to the etiological heterogeneity of the clinical, psychopathologically defined phenotype of the disease. Neurobiological correlates of the disease which are genetically influenced and stable over time are considered to be more promising targets of phenotypes. They are more directly influenced by gene effects and presumably defined by a genetic determination which is less complex than the phenotype of the disorder. The endophenotype strategy has already been successful in complex disorders of other areas in medicine, including alcoholism and late-onset Alzheimer's disease. For schizophrenia, a series of endophenotypes for molecular/genetic investigation has been suggested, but the concept "endophenotype" also provides a basis for biological classification of mental disorders.

Alcoholism↗

Examination of G72 and D-amino-acid oxidase as genetic risk factors for schizophrenia and bipolar affective disorder.

A recent study has suggested that the brain-expressed genes for G72 and D-amino-acid oxidase (DAAO) exert an influence on susceptibility to schizophrenia. Our aim was to replicate this finding in German schizophrenic patients and to assess whether G72 and DAAO might also contribute to the development of bipolar affective disorder. We genotyped seven single-nucleotide polymorphisms (SNPs) in the G72 gene and three in the DAAO gene in 599 patients (299 schizophrenic, 300 bipolar) and 300 controls. At G72, individual SNPs and a four-marker haplotype were associated with schizophrenia. The most significant SNP as well as the haplotype were also associated with bipolar affective disorder (BPAD). DAAO was associated with schizophrenia, but not with BPAD. The association of variation at G72 with schizophrenia as well as BPAD provides molecular support for the hypothesis that these two major psychiatric disorders share some of their etiologic background.

Adult↗

Erythropoietin: a candidate compound for neuroprotection in schizophrenia.

Erythropoietin (EPO) is a candidate compound for neuroprotection in human brain disease capable of combating a spectrum of pathophysiological processes operational during the progression of schizophrenic psychosis. The purpose of the present study was to prepare the ground for its application in a first neuroprotective add-on strategy in schizophrenia, aiming at improvement of cognitive brain function as well as prevention/slowing of degenerative processes. Using rodent studies, primary hippocampal neurons in culture, immunohistochemical analysis of human post-mortem brain tissue and nuclear imaging technology in man, we demonstrate that: (1) peripherally applied recombinant human (rh) EPO penetrates into the brain efficiently both in rat and humans, (2) rhEPO is enriched intracranially in healthy men and more distinctly in schizophrenic patients, (3) EPO receptors are densely expressed in hippocampus and cortex of schizophrenic subjects but distinctly less in controls, (4) rhEPO attenuates the haloperidol-induced neuronal death in vitro, and (4) peripherally administered rhEPO enhances cognitive functioning in mice in the context of an aversion task involving cortical and subcortical pathways presumably affected in schizophrenia. These observations, together with the known safety of rhEPO, render it an interesting compound for neuroprotective add-on strategies in schizophrenia and other human diseases characterized by a progressive decline in cognitive performance.

Adult↗

Multicenter linkage study of schizophrenia loci on chromosome 22q.

The hypothesis of the existence of one or more schizophrenia susceptibility loci on chromosome 22q is supported by reports of genetic linkage and association, meta-analyses of linkage, and the observation of elevated risk for psychosis in people with velocardiofacial syndrome, caused by 22q11 microdeletions. We tested this hypothesis by evaluating 10 microsatellite markers spanning 22q in a multicenter sample of 779 pedigrees. We also incorporated age at onset and sex into the analysis as covariates. No significant evidence for linkage to schizophrenia or for linkage associated with earlier age at onset, gender, or heterogeneity across sites was observed. We interpret these findings to mean that the population-wide effects of putative 22q schizophrenia susceptibility loci are too weak to detect with linkage analysis even in large samples.

Chromosome Mapping↗

[Early course of illness in first episode schizophrenia with long duration of untreated illness - a comparative study].

When a long duration of untreated illness (DUI) is correlated with an unfavourable progression of schizophrenia in the same way as that of a long duration of untreated psychosis (DUP), the characteristics of patients with a long DUI are of particular interest for early recognition and early intervention programmes. With this background, demographic data and early symptoms were collected from 82 first time in-patients with schizophrenia using the IRAOS (Interview for the Retrospective Assessment of the Onset of Schizophrenia). In the total sample, the average DUI was almost 5.9 years. On the basis of the DUI median (5.2 yrs), the random sample was divided into two groups: one with long (n = 41) and one with short (n = 41) DUI. When comparing both groups in terms of socio-demographic data, no significant differences could be found (with the exception of age at first admission: 28 - 32 yrs). On a psychopathological level, patients with long DUI were prone to depressive moods, anxiety, compulsive symptoms and showed early signs of disturbances in bodily perception. An educational campaign should sensitize both employees working in primary care and experts who diagnose and treat psychological illnesses, to the fact that these symptoms could point to a prodrome even when the patient has passed the typical age of being at risk from schizophrenia.

Adolescent↗

[Does computer-aided navigation of endonasal sinus surgery improve process quality and outcome quality?].

BACKGROUND: Ever since navigation technology was introduced into endonasal surgery, its impact on process and result of surgery has been debated. In this respect, factors of investment costs and additional costs for time exposure will be discussed as well. PATIENTS AND METHODS: In a retrospective analysis of quality assurance, the results of endonasal surgery by surgeons of different experience in 56 patients were evaluated. Preparation time, preoperative setup time as well as time of actual surgery were analysed and compared with possible indications for navigation. RESULTS: From our analysis a classification resulted dividing the indications for navigation into the following four different categories: redundant, reasonable, helpful, necessary. Navigation was redundant when it was dispensable and did not result in a clear improvement of process or outcome quality. Navigation has been proved reasonable when it helped to obtain additional information for improving process quality. It was considered helpful when the information obtained by navigation had an influence at least on the course and/or result of surgery. Navigation was necessary from the surgeon's point of view when the intervention in regard to the benefit-risk-ratio could not be justified without navigation, or only intraoperative slice imaging would allow surgery. CONCLUSION: Not only redundant, but also facultative and obligatory indications for navigation in endonasal surgery result from careful consideration of the risk-benefit-cost ratio. In standardized endonasal sinus surgery, like infundibulotomy or ethmoidectomy, however, navigation can be a hindrance to process quality and does not result in any advantage for outcome quality.

Adult↗

[Tumour staged surgery of endolymphatic sac tumors (ELST)].

BACKGROUND: Endolymphatic sac tumours (ELST) have only been known as own tumour entities since 1984. ELST might occur solitarily and sporadically as well as hereditary connected to von Hippel-Lindau disease (VHL). This connection has been observed in 1992 for the first time and confirmed by molecular genetic analyses of the VHL gen. There is no agreement yet concerning diagnostics and therapy. METHODS: Our attempt of classifying this type of tumour is the first one. According to our own experience and to literature, we suggest the following classification: ELST type A is locally confined without erosions of the temporal bone nor infiltration of the subarachnoidal area; ELST type B with bony infiltration of the labyrinth block and clinical hearing loss, and ELST type C with additional infiltration of the sigmoid sinus and the vein of jugular bulb. Preoperative diagnostics are performed according to defined radiological criteria in CT and MRI scans including MR-angiography. RESULTS: In 6 patients, including two with a VHL syndrome, ELST was completely sanitized by stage-compatible surgery, using translabyrintine to infratemporal approaches, according to the tumour classification that we developed. The VII (th) nerve could be saved in all tumour stages, and in stage ELST type A the VIII (th) nerve as well. All patients remained without local recurrence in MRI check during the observation period of 4 to 38 months. CONCLUSION: Our stage-compatible surgery of ELST allows total tumor removal with minor morbidity. In contrast to the antero-, retrosigmoidal and suboccipital approaches, the tumour matrix can be safely removed via transmastoidal approach to exclude local recurrences.

Adult↗

[Diagnosis and management of cervical paragangliomas: the Freiburg experience].

BACKGROUND: Paragangliomas of the head and neck represent rare tumors of neural crest origin that arise from chemoreceptors. They are highly vascular neoplasms that are benign in the majority of cases. There are controversial discussions concerning the different treatment options for cervical paragangliomas. PATIENTS: Between January 1992 and November 2003 a total of 13 patients with 15 cervical paragangliomas were treated at the Department of Otorhinolaryngology - Head and Neck Surgery, University of Freiburg. Our study includes eight female and five male patients with a mean age of 39.9 years (range: 20 - 79 years). There were 14 carotid body tumors and one vagal paraganglioma. RESULTS: 14 tumors were resected and one underwent primary radiation. In four patients we noted a total of 8 permanent, postoperative nerve deficits. During follow-up no recurrent tumors were seen. CONCLUSION: Complete surgical removal represents the therapy of choice for the majority of cervical paragangliomas. In cases of multiple head and neck paragangliomas or in patients with underlying diseases, primary radiation should be discussed as a treatment option.

Adult↗

[Subtemporal approach according to house versus Wigand in intrameatal CPA tumors type A].

BACKGROUND: The subtemporal approach is indicated in intrameatal CPA tumors type A in order to preserve hearing. The exploration of the inner auditory canal for tumor exposure varies. It reaches from a locally limited uncovering of the bony inner auditory canal to a complete removal of the surrounding bony bed with the circular skeletization (360 degrees ) according to Wigand of the 7 (th) and 8 (th) nerve. Concerning the preservation of the function of the cranial nerve as well as an avoidable hyperelevation of the temporal cerebral lobe with a possible consecutive organic brain syndrome, both approaches have often been discussed controversially. METHOD: In a quality assurance analysis, we examined patients suffering from a unilateral, intrameatally limited CPA tumor type A in tumor stages 1 to 5. The functions of the 7 (th) and 8 (th) cranial nerves were assessed according to the consensus conference "Systems for reporting results in acoustic neuroma", Tokyo, November 2001, under consideration of the recommendations of the "American Academy of Otolaryngology, Head and Neck Surgery -- Committee on hearing and equilibrium guidelines for the evaluation of hearing preservation in acoustic neuroma", 1995, as well as indications for a possible organic brain syndrome. The results then were compared to current literature. RESULTS: 37 patients with an intrameatal confined CPA tumor after subtemporal tumor exstirpation were evaluated. In these patients, the inner auditory canal was only exposed in the area of the bony tectum (90 degrees - 120 degrees ) adjusted to the volume of the tumor, as described by House: 1 patient with tumor stage 1, 2 patients stage 2, 12 patients stage 3, 16 patients stage 4 and 6 patients with a tumor stage 5. The N. VII was anatomically preserved in 100 %. Immediately after surgery the function of N. VII was assessed in 32 % of the cases as stage I, 43 % stage II, 3 % stage IIIa, 14 % stage IIIb, 3 % stage IV, 0 % stage V, 5 % stage VI. All patients in stage VI had a restricted function of N. VII in stage II or IIIa already before surgery. N. VIII could be preserved anatomically in 78 % of the cases. 1 to 6 months postoperatively the hearing was at stage A in 10 % of the cases, at 25 % in stage B, 33 % in stage C, 16 % in stage D, 5 % in stage E and 11 % in stage F. One patient demonstrated signs of a possible organic brain syndrome postoperatively even after 12 months of latency (headache, unsteady walking, attention disorders). CONCLUSION: When comparing own data with the clinical results from literature, no differences can be found concerning the function of the 7 (th) and 8 (th) cranial nerves. There are no data concerning the incidence of a potential organic brain syndrome. The advantage of the House method is a noticeably reduced drilling time as well as possibly a reduced elevation of the temporal cerebral lobes. The Wigand method, however, allows a better overview and is needed for extrameatally growing tumors anyway.

Cranial Nerve Injuries↗