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Biomedical subjects

U Müller

Publications and source records attributed to U Müller.

At least 19 recordsLinked to original sources
PubMed2006

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

Adolescent↗
PubMed2006

Assessment of body composition of patients with COPD.

The intention of the study was to determine nutritional state and body cell mass in patients with COPD in comparison with healthy volunteers between 50 and 75 years of age. Therefore, body cell mass (BCM), phase angle and the relation between extra cellular mass and body cell mass ECM/BCM was measured with the help of bioelectrical impedance analysis (BIA). While 10.4 % of COPD patients (male 5.0 %, female 18.8 %) had a BMI of < 18.5, no subject was underweight in the healthy volunteers. Overweight was found in 31.7 % patients (male 36.0 %, female 25.0 %) and in 54.2 % healthy subjects (male: 62.5 %, female 46.9 %), 17.1 % of our patients (male 16.0 %, female 18.8 %) versus 21.7 % of healthy subjects (male 14.3 %, female 28.1 %) were obese. While there was no statistic significance for a lower BMI in COPD patients, there were significantly decreased values concerning muscle mass -- represented by BCM-values -- and state of nutrition -- represented by BCM, phase angle and ECM/BCM values -- in COPD patients compared with healthy volunteers. These results suggest that BMI alone doesn't allow conclusions regarding to nutritional state and physical training. A malnutrition requiring intervention might exist in spite of a normal or even high BMI in COPD patients.

Aged↗
PubMed2006

Do human osteoblasts grow into open-porous titanium?

A titanium foam for spine fusion and other applications was tested by cell culture. Its high porosity and surface roughness should enable bone cells to grow through it, resulting in a better fixation of the vertebral body. The foam was tested by in vitro experiments with human osteoblasts under static culture conditions and in a perfused system. By means of cell number, viability, scanning electron microscopy and histological staining, cell proliferation could be observed. The expression of osteogenic genes like collagen-I, alkaline phosphatase and osteocalcin was proven by reverse transcription polymerase chain reaction (RT-PCR) as well as in the case of alkaline phosphatase with biochemical methods. The conducted experiments showed that human osteoblasts could grow through the interconnected porosity of the metal foam and that they expressed an osteoblast like phenotype. The results suggest that in vivo osteoblasts are likely to form a trabecular bone bridge through this titanium foam. Consequently, with this osteoconductive material, there may be a reduced need for autologous bone in spinal fusion procedures.

Alkaline Phosphatase↗
PubMed2006

Avoiding misclassification bias with the traditional Charnley classification: rationale for a fourth Charnley class BB.

Long-term follow up of patients with total hip arthroplasty (THA) revealed a marked deterioration of walking capacities in Charnley class B after postoperative year 4. We hypothesized that a specific group of patients, namely those with unilateral hip arthroplasty and an untreated but affected contralateral hip was responsible for this observation. Therefore, we conducted a study taking into consideration the two subclasses that make up Charnley class B: patients with unilateral THA and contralateral hip disease and patients with bilateral THA. A sample of 15,160 patients with 35,773 follow ups that were prospectively collected over 10 years was evaluated. The sample was categorized into four classes according to a new modified Charnley classification. Annual analyses of the proportion of patients with ambulation longer than 60 min were conducted. The traditionally labeled Charnley class B consists of two very different patient groups with respect to their walking capacities. Those with unilateral THA and contralateral hip disease have underaverage walking capacities and a deterioration of ambulation beginning 3 to 4 years after surgery. Those with bilateral THA have stable overaverage walking capacities similar to Charnley class A. An extension of the traditional Charnley classification is proposed, taking into account the two different patient groups in Charnley class B. The new fourth Charnley class consists of patients with bilateral THA and was labeled BB in order to express the presence of two artificial hip joints and to preserve the traditional classification A through C.

Adult↗
PubMed2006

Comprehensive genomic analysis of desmoplastic medulloblastomas: identification of novel amplified genes and separate evaluation of the different histological components.

Desmoplastic medulloblastoma (DMB) is a malignant cerebellar tumour composed of two distinct tissue components, pale islands and desmoplastic areas. Previous studies revealed mutations in genes encoding members of the sonic hedgehog pathway, including PTCH, SMOH and SUFUH in DMBs. However, little is known about other genomic aberrations. We performed comparative genomic hybridization (CGH) analysis of 22 sporadic DMBs and identified chromosomal imbalances in 20 tumours (91%; mean, 4.9 imbalances/tumour). Recurrent chromosomal gains were found on chromosomes 3, 9 (six tumours each), 20, 22 (five tumours each), 2, 6, 7, 17 (four tumours each) and 1 (three tumours). Recurrent losses involved chromosomes X (eight tumours), Y (six of eleven tumours from male patients), 9, 12 (four tumours each), as well as 10, 13 and 17 (three tumours each). Four tumours demonstrated high-level amplifications involving sequences from 1p22, 5p15, 9p, 12p13, 13q33-q34 and 17q22-q24, respectively. Further analysis of the 9p and 17q22-q24 amplicons by array-based CGH (matrix-CGH) and candidate gene analyses revealed amplification of JMJD2C at 9p24 in one DMB and amplification of RPS6KB1, APPBP2, PPM1D and BCAS3 from 17q23 in three DMBs. Among the 17q23 genes, RPS6KB1 showed markedly elevated transcript levels as compared to normal cerebellum in five of six DMBs and four of five classic medulloblastomas investigated. Finally, CGH analysis of microdissected pale islands and desmoplastic areas showed common chromosomal imbalances in five of six informative tumours. In summary, we have identified several novel genetic alterations in DMBs and provide genetic evidence for a monoclonal origin of their different tissue components.

Base Sequence↗
PubMed2006

Dynamic memory networks: dissecting molecular mechanisms underlying associative memory in the temporal domain.

The molecular mechanisms underlying the induction and maintenance of memory are highly dynamic and comprise distinct phases covering a time window from seconds to even a lifetime. Neuronal networks, which contribute to these processes, have been extensively characterized on various levels of analysis, and imaging techniques allow monitoring of both gross brain activity as well as functional changes in defined brain areas during the time course of memory formation. New techniques developed in honeybees and fruit flies even allow for manipulation of neuronal networks and molecular cascades in a short temporal domain while a living animal under observation acquires new associative memories. These advantages make honeybees and flies ideal organisms to study transient molecular events underlying dynamic memory processing in vivo. In this review we will focus on the temporal features of molecular processes in learning and memory formation, summarize recent knowledge and present an outlook on future developments.

Animals↗
PubMed2006

[Procedures of temporary wall closure in abdominal trauma and sepsis].

Temporary abdominal closure methods differ mainly between vacuum-assisted and conventional approaches. Each method has its indications. Vacuum-assisted methods seem to be superior especially for trauma indications--in terms of lethality, the possibility of secondary closure during primary hospital stay, and frequency of enterocutaneous fistulas. Skin-only closure might be used as a short-term application (e.g. when damage control closure is needed), and the Bogota bag silo gives space to protruding bowels in pending or manifest abdominal compartment syndrome. Temporary fascial mesh closure enables repetitive laparotomies through the mesh, thus sparing the fascia. For that reason it is to be preferred, especially for its good practicability in clinical situations and on mission abroad.

Abdominal Injuries↗
PubMed2005

The rationale for a spine registry.

In the discussion about the rationale for spine registries, two basic questions have to be answered. The first one deals with the value of orthopaedic registries per se, considering them as observational studies and comparing the evidence they generate with that of randomised controlled trials. The second question asks if the need for registries in spine surgery is similar to that in the arthroplasty sector. The widely held view that randomised controlled trials are the 'gold standard' for evaluation and that observational methods have little or no value ignores the limitations of randomised trials. They may prove unnecessary, inappropriate, impossible, or inadequate. In addition, the external validity and hence the ability to make generalisations about the results of randomised trials is often low. Therefore, the false conflict between those who advocate randomised trials in all situations and those who believe observational data provide sufficient evidence needs to be replaced with mutual recognition of their complementary roles. The fact that many surgical techniques or technologies were introduced into the field of spine surgery without randomised trials or prospective cohort comparisons makes obvious an even increased need for spine registries compared to joint arthroplasty. An essential methodological prerequisite for a registry is a common terminology for reporting results and a sophisticated technology that networks all participants so that one central data pool is created and accessed. Recognising this need, the Spine Society of Europe has researched and developed Spine Tango, the first European spine registry, which can be accessed under www.eurospine.org.

Arthroplasty↗
PubMed2005

An autosomal dominant ataxia maps to 19q13: Allelic heterogeneity of SCA13 or novel locus?

The autosomal dominant spinocerebellar ataxias (ADCAs) represent a growing and heterogeneous disease phenotype. Clinical characterization of a three-generation Filipino family segregating a dominant ataxia revealed cerebellar signs and symptoms. After elimination of known spinocerebellar ataxia (SCA) loci, a genome-wide linkage scan revealed a disease locus in a 4-cM region of 19q13, with a 3.89 lod score. This region overlaps and reduces the SCA13 locus. However, this ADCA is clinically distinguishable from SCA13.

Adult↗
PubMed2005

The Alzheimer variant of lewy body disease: a pathologically confirmed case-control study.

The objective of the study was to identify clinical features that distinguish patients with dementia with Lewy bodies (DLB), who were classified as Alzheimer's disease (AD) patients, from patients with AD. We examined a group of 27 patients from our memory clinic, originally diagnosed with AD, of whom 6 were postmortem found to have DLB. For the present study, we compared cognitive, noncognitive and neurological symptoms between the two groups. We found that there were no differences on ratings of dementia and scales for activities of daily living. Patients with DLB performed better on the MMSE and the memory subtest of the CAMCOG, but there was no difference in any other cognitive domain. Furthermore, genetic risk factors, including family history of dementia or allele frequency of the apolipoprotein epsilon4, did not discriminate between the two groups, and there were no differences on CCT scans. Taken together, our findings suggest that Lewy body pathology may be present in patients who do not show the typical clinical features which distinguish DLB from AD.

Aged↗
PubMed2005

Arteries in the posterior cervical triangle in man.

Due to frequent changes in the anatomical nomenclature of the arteries in the posterior cervical triangle (lateral cervical region), anatomical and surgical papers relating to these topics are sometimes difficult to understand and are hard to compare. These changes, coupled with improper knowledge of the gross anatomy and nomenclature of the arteries in the posterior cervical triangle, have presented difficulties in musculocutaneous flap planning, especially in plastic and reconstructive surgery. As an illustration of this concern, the term, transverse cervical artery (A. transversa colli [cervicis]), and its associated branches, have been used frequently over the past several decades with different meanings. In an effort to address this nomenclature challenge and to offer a rational basis for arguing specific name changes, a total of 498 neck-halves were investigated in Graz, Innsbruck, and Munich. Lateral neck dissections were carried out to expose the subclavian artery and those branches destined for the posterior cervical triangle, specifically, the superficial cervical artery, the dorsal scapular artery, and the suprascapular artery. The course of these arteries and details of their origins and branching patterns were documented. Several arose either as direct branches or from trunks. The convention used in labeling trunks was similar to that described for other trunk formations in the body (e.g., linguo-facial trunk). Four trunks were observed and named according to the branches that arose from each. A cervico-dorsal trunk gave origin to the superficial cervical and dorsal scapular arteries, and was found in 30% of cases. A cervico-scapular trunk gave rise to the superficial cervical and suprascapular arteries in 22% of cases, and a dorso-scapular trunk provided origins for the dorsal scapular and suprascapular arteries in 4% of cases. A cervico-dorso-scapular trunk gave origin to the superficial cervical artery, the dorsal scapular artery, and the suprascapular artery, and was found in 24% of cases. Each of these trunks, in turn, arose from either the subclavian artery or from the thyrocervical trunk. This labeling convention necessitated omitting the term, transverse cervical artery, because this term has become inherently imprecise and variously used over the years. This study describes a simple, uniform, and rational basis for standardizing the nomenclature of the arteries in the posterior cervical triangle.

Aged↗
PubMed2005

[Indication for removal of tibial nails].

BACKGROUND: Tibial nail removal has been suggested as a routine procedure for both symptomatic and asymptomatic patients. The aim of this study was to define guidelines for the removal of tibial nails. PATIENTS AND METHODS: A retrospective study on the isolated removal of 69 tibial nails after fracture consolidation was done. A review of the patient charts and radiographs was performed. Forty-four patients (64%) were available for the follow-up interview. RESULTS: Preoperatively, 26 patients (59%) had local complaints. Of these 26 patients, 73% reported an improvement, and 8% reported an aggravation of their local complaints. Of the 18 patients who were asymptomatic before surgery, 17% reported long-term complaints at follow-up. CONCLUSION: We conclude that routine removal of tibial nails should be discussed critically in asymptomatic patients.

Adolescent↗
PubMed2005

Prefrontal cognitive deficits in patients with schizophrenia treated with atypical or conventional antipsychotics.

Forty-three patients with schizophrenia were investigated with a short neurocognitive screening battery focussing on working memory and executive functions. As compared to healthy controls, patients showed impairments in the modified card sorting test, in verbal fluency and all span tasks with exception of digit span forward. Patients who were treated with atypicals showed better performance in the digit ordering test (manipulation task) when compared to a group of patients who received conventional antipsychotics; this difference was not due to disease severity, age or education. Manipulation tasks might be useful for neurocognitive follow-up and intervention studies.

Adult↗
PubMed2005

Lengthening of G2/mitosis in cortical precursors from mice lacking beta-amyloid precursor protein.

The beta-amyloid precursor protein (APP) is expressed within the nervous system, even at the earliest stages of embryonic development when cell growth and proliferation is particularly important. In order to study the function of APP at these early developmental stages, we have studied the development of the cerebral cortex in both wild type and App-/- mutant mice. Here, we demonstrate that APP mRNA is expressed in cortical precursor cells and that APP protein is concentrated within their apical domains during interphase. However, during mitosis, APP re-localizes to the peripheral space surrounding the metaphase plate. In APP-deficient cortical precursors, the duration of mitosis is increased and a higher proportion of cortical precursor cells contained nuclei in late G2. We conclude that during cortical development APP plays a role in controlling cell cycle progression, particularly affecting G2 and mitosis. These observations may have important implications for our understanding of how APP influences the progression of Alzheimer's disease, since degenerating cortical neurons have been shown to up-regulate cell cycle markers and re-enter the mitotic cycle before dying.

Amyloid beta-Protein Precursor↗
PubMed2005

Determination of cyclosporine and its metabolites in blood via HPLC-MS and correlation to clinically important parameters.

The narrow therapeutic window of the immunosuppressive drug cyclosporine (CsA), the interindividual variability of its metabolism, and the immunosuppressive activity/toxicity of some metabolites require investigation to correlate the parent substance and its metabolites and observed clinical parameters. Improved knowledge about these correlations may improve postoperative treatment of transplant patients. To observe such correlation therapeutic drug monitoring was performed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) on 202 blood samples of kidney transplant patients. As CsA and its metabolites are preferably bound to lipoproteins in vivo, sample preparation included protein precipitation, solid phase extraction, and separation on a reversed phase column. Mass-spectrometric detection by an electrospray ionization chamber made the detection and quantification of the sodium adducts of CsA and its metabolites AM1, AM1c, DihydroAM1, AM19, and AM4N possible. With the presented HPLC-MS method, rapid information was achieved about the specific metabolization in a patient. Statistical computations related CsA and its metabolite concentrations to clinically important blood parameters. Significant correlation to the blood level of bilirubin and liver enzymes confirmed the presumed hepatotoxic potential of CsA and some metabolites. Furthermore, a strong correlation of AM19 to CRP and IL6 was observerd. These parameters may influence the prognosis for atherosclerosis, inflammation, and chronic allograft nephropathy.

Alanine Transaminase↗
PubMed2005

SCN1A mutation analysis in myoclonic astatic epilepsy and severe idiopathic generalized epilepsy of infancy with generalized tonic-clonic seizures.

Severe myoclonic epilepsy in infancy (SMEI), severe idiopathic generalized epilepsy of infancy (SIGEI) with generalized tonic clonic seizures (GTCS), and myoclonic astatic epilepsy (MAE) may show semiological overlaps. In GEFS+ families, all three phenotypes were found associated with mutations in the SCN1A gene. We analyzed the SCN1A gene in 20 patients with non-familial myoclonic astatic epilepsy -- including 12 probands of the original cohort used by Doose et al. in 1970 to delineate MAE. In addition, 18 patients with sporadic SIGEI -- mostly without myoclonic-astatic seizures -- were analyzed. Novel SCN1A mutations were found in 3 individuals. A frame shift resulting in an early premature stop codon in a now 35-year-old woman with a borderline phenotype of MAE and SIGEI (L433fsX449) was identified. A splice site variant (IVS18 + 5 G --> C) and a missense mutation in the conserved pore region (40736 C --> A; R946 S) were detected each in a child with SIGEI. We conclude that, independent of precise syndromic delineation, myoclonic-astatic seizures are not predictive of SCN1A mutations in sporadic myoclonic epilepsies of infancy and early childhood.

Child↗
PubMed2005

[Studies on the recovery of pharmaceutical drug substances from surfaces made of defined stainless-steel alloys].

Facilities for the manufacturing of pharmaceutical drug substances on the pilot-plant and the industrial scale as well as chemical reactors and vessels used for chemical work-up mainly consist of alloyed stainless steel. The influence of the alloy composition and the surface condition, i.e. of the roughness of the stainless-steel materials, on the adsorption of structurally diverse steroidal substances and, hence, on the quality of the products was studied. In general, stainless-steel alloys with smooth, not so rough surfaces are to be favored as reactor material. However, it was demonstrated in this study that, on account of the weak interaction between active substances and steel materials, mechanically polished materials of a medium roughness up to approx. 0.4 microm can be employed instead of the considerably more cost-intensive electrochemically polished stainless-steel surfaces. The type of surface finishing up to a defined roughness, then, has no influence on the quality of these pharmaceutical products. Substances that, because of their molecular structure, can function as "anions" in the presence of polar solvents, are adsorbed on very smooth surfaces prepared by electrochemical methods, forming an amorphous surface film. For substances with this structural characteristics, the lower-cost mechanically polished reactor materials of a medium roughness up to approx. 0.5 microm should be used exclusively.

Algorithms↗