Biomedical subjects

R Schmidt

Publications and source records attributed to R Schmidt.

At least 19 recordsLinked to original sources

PubMed2006

Plasma creatinine determination in mice and rats: an enzymatic method compares favorably with a high-performance liquid chromatography assay.

The use of the colorimetric Jaffé method for the measurement of creatinine in mouse and rat plasma has been criticized as prior studies have shown a dramatic overestimation. We compared a colorimetric picric acid, an enzymatic, and a high-performance liquid chromatography (HPLC) method to assess their appropriateness for routine measurements of creatinine in plasma of healthy and diseased mice (n=61) and rats (n=56). For the colorimetric Jaffé method a pronounced overestimation is confirmed. Additionally the method showed interference with hemoglobin already in a very low, non-visible concentration range in rat plasma. The enzymatic measurement demonstrated a hemoglobin interference in mice, only when hemolysis was visible. The comparison between HPLC and the enzymatic measurement gave a good agreement between both methods in both species. Therefore the enzymatic method fulfills the requirements for a routine screening test for plasma creatinine in healthy as well as diseased mice and rats Kiover a broad concentration range.

Amidohydrolases↗

PubMed2006

Design of a computer-controlled multileaf collimator for advanced electron radiotherapy.

A multileaf collimator for electrons (eMLC) has been designed that fulfils the technical requirements for providing advanced irradiation techniques with electrons. In the present work, the basic design parameters of leaf material, leaf height, leaf width and number of leaves as well as leaf overtravel and leaf shape were determined such that an eMLC with motorized leaves can be manufactured by a company specialized in MLC technology. For this purpose, a manually driven eMLC with variable source-to-collimator distance (SCD) was used to evaluate the chosen leaf specification and investigate the impact of the SCD on the off-axis dose distribution. In order to select the final SCD of the eMLC, a compromise had to be found between maximum field size, minimum beam penumbra and necessary distance between eMLC and isocentre to eliminate patient realignments during gantry rotation. As a result, the eMLC is placed according to the target position at 72 and 84 cm SCD, respectively. This feature will be achieved by interchangeable distance holders. At these SCDs, the corresponding maximum field sizes at 100 cm source-to-isocentre distance are 20 x 20 cm and 17 x 17 cm, respectively. Finally, the off-axis dose distribution at the maximum opening of the eMLC was improved by fine-tuning the settings of the accelerator jaws and introducing trimmer bars above the eMLC. Following this optimization, a prototype eMLC consisting of 2 x 24 computer-controlled brass leaves is manufactured by 3D Line Medical Systems.

Biophysical Phenomena↗

PubMed2006

Quantitative computer-assisted osteodensitometry in total hip arthroplasty.

Several factors can cause bone loss and fixation failure following total hip arthroplasty (THA), including polyethylene wear debris, implant micromotion and stress shielding. Various techniques have been used in an effort to detect bone density loss in vivo, all with varying success. Quantitative computed tomography (qCT)-assisted osteodensitometry has been shown to be useful in assessing the in vivo structural bone changes after THA. It has a high resolution, accuracy and reproducibility, thereby making it a useful tool for research purposes, and it is able to differentiate between cortical and cancellous bone structures and assess the bone/implant interface. This technique also provides valuable information about the pattern of stress shielding which occurs around the prosthesis and can show early bony changes, which may prove informative about the quality of implant fixation and surrounding bone adaptation. In conjunction with finite-element analysis, qCT is able to generate accurate patient-specific meshes on which to model implants and their effect on bone remodelling. This technology can be useful to predict bone remodelling and the quality of implant fixation using prostheses with different design and/or biomaterials. In the future, this tool could be used for pre-clinical validation of new implants before their introduction in the market-place.

Absorptiometry, Photon↗

PubMed2006

A comparative linkage map of oilseed rape and its use for QTL analysis of seed oil and erucic acid content.

We have developed a new DH mapping population for oilseed rape, named TNDH, using genetically and phenotypically diverse parental lines. We used the population in the construction of a high stringency genetic linkage map, consisting of 277 loci, for use in quantitative genetic analysis. A proportion of the markers had been used previously in the construction of linkage maps for Brassica species, thus permitting the alignment of maps. The map includes 68 newly developed Sequence Tagged Site (STS) markers targeted to the homologues of defined genes of A. thaliana. The use of these markers permits the alignment of our linkage map with the A. thaliana genome sequence. An additional 74 loci (31 newly developed STS markers and 43 loci defined by SSR and RFLP markers that had previously been used in published linkage maps) were added to the map. These markers increased the resolution of alignment of the newly constructed linkage map with existing Brassica linkage maps and the A. thaliana genome sequence. We conducted field trials with the TNDH population at two sites, and over 2 years, and identified reproducible QTL for seed oil content and erucic acid content. The results provide new insights into the genetic control of seed oil and erucic acid content in oilseed rape, and demonstrate the utility of the linkage map and population.

Brassica napus↗

PubMed2006

Surfactant protein C mutations in sporadic forms of idiopathic interstitial pneumonias.

Interstitial pneumonias have recently been associated with mutations in the gene encoding surfactant protein C (SFTPC). In particular, SFTPC mutations have been reported in a number of familial forms of pulmonary fibrosis and in infants with interstitial lung diseases. The present study searched for SFTPC mutations in adult patients with sporadic idiopathic interstitial pneumonia. In total, 35 adult patients with sporadic idiopathic interstitial pneumonia and 50 healthy subjects were investigated for SFTPC mutations by direct DNA sequencing. Of the patients with sporadic idiopathic interstitial pneumonia, 25 suffered from idiopathic pulmonary fibrosis and 10 patients from nonspecific interstitial pneumonia. Only two frequent nonsynonymous variants, T138N and S186N, were detected. Allele frequencies of both variations as well as of other identified noncoding alterations did not differ significantly between the diverse patient groups and control subjects. In conclusion, mutations in the gene encoding surfactant protein C are not common in sporadic cases of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia, suggesting that the mutated gene does not play an important role in the pathogenesis of these forms of idiopathic interstitial pneumonia.

Adult↗

PubMed2006

Simple versus complex assessment of white matter hyperintensities in relation to physical performance and cognition: the LADIS study.

BACKGROUND: White matter hyperintensities (WMH) on MRI are associated with disorders of gait and balance and with cognitive impairment. The most suitable method to assess WMH in relation to the clinical evaluation of disturbances in these areas has not yet been established. AIM: To compare a simple visual rating scale, a detailed visual rating scale and volumetric assessment of WMH with respect to their associations with clinical measures of physical performance and cognition. METHODS: Data were drawn from the multicentre, multinational LADIS study. Data of 574 subjects were available. MRI analysis included assessment of WMH using the simple Fazekas scale, the more complex Scheltens scale and a semi-automated volumetric method. Disturbances of gait and balance and general cognitive function were assessed using the Short Physical Performance Battery (SPPB) and the Mini Mental State Examination (MMSE), respectively. RESULTS: Irrespective of the method of measuring WMH, subjects with disturbances of gait and balance (SPPB < or = 10) had more WMH than subjects with normal physical performance. Subjects with mild cognitive deficits (MMSE < or = 25) had more WMH than subjects with normal cognition. Correlations between clinical measures and WMH were equal across methods of WMH measurement (SPPB: Spearman r = -0.22, -0.25, -0.26, all p < 0.001; MMSE: Spearman r = -0.11, -0.10, -0.09, all p < 0.05, for Fazekas scale, Scheltens scale and volumetry, respectively). These associations remained significant and comparable after correcting for age, gender and education in multivariate linear regression analyses. CONCLUSION: Simple and complex measures of WMH yield comparable associations with measures of physical performance and cognition. This suggests that a simple visual rating scale may be sufficient, when analyzing relationships between clinical parameters and WMH in a clinical setting.

Aged↗

PubMed2006

Clinical significance of corpus callosum atrophy in a mixed elderly population.

Corpus callosum (CC) is the main tract connecting the hemispheres, but the clinical significance of CC atrophy is poorly understood. The aim of this work was to investigate clinical and functional correlates of CC atrophy in subjects with age-related white matter changes (ARWMC). In 569 elderly subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented on the normalised mid-sagittal magnetic resonance imaging (MRI) slice and subdivided into five regions. Correlations between the CC areas and subjective memory complaints, mini mental state examination (MMSE) score, history of depression, geriatric depression scale (GDS) score, subjective gait difficulty, history of falls, walking speed, and total score on the short physical performance battery (SPPB) were analyzed. Significant correlations between CC atrophy and MMSE, SPPB, and walking speed were identified, and the CC areas were smaller in subjects with subjective gait difficulty. The correlations remained significant after correction for ARWMC grade. In conclusion, CC atrophy was independently associated with impaired global cognitive and motor function in subjects with ARWMC.

Age Factors↗

PubMed2006

The phenomenon and efficiency of ligamentotaxis after dorsal stabilization of thoracolumbar burst fractures.

Thirty-six consecutive patients with burst fractures of the thoracolumbar spine and with a fractured posterior vertebral surface dislocated into the spinal canal without neurological symptoms were treated with the AO internal fixator. Computed tomography-aided planimetry of the spinal canal was undertaken preoperatively and within 1 week postoperatively to elucidate the effect of kyphosis correction and distraction on spinal canal widening (ligamentotaxis). The stenosis of the spinal canal area (SCA) was reduced from 29% preoperatively to 19% postoperatively (+10%) of the estimated original area, and the stenosis of the mid-sagittal diameter (MSD) reduced from 31 to 23% (+8%). The widening of the SCA was greater at the level of L1/L2 (+13%) than at L3/L4 (+6%). High preoperative canal compromise was associated with greater absolute spinal canal widening. Large trapezoid-shaped fragments resisted reduction by ligamentotaxis. Even though the effect of ligamentotaxis after operative treatment with the internal fixator was proven, a certain stenosis of the spinal canal remains in most cases. Especially for patients with fracture-related neurological symptoms, ligamentotaxis alone does not seem sufficient for the requested spinal decompression. Even an exact analysis of preoperative CT scans under consideration of the fracture level will not always allow an exact prognosis of the expected effect of ligamentotaxis.

Adolescent↗

PubMed2006

APOE epsilon variation in multiple sclerosis susceptibility and disease severity: some answers.

BACKGROUND: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. METHODS: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. RESULTS: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of epsilon2 or epsilon4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96-1.34 and OR 0.89, 95% CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. CONCLUSION: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.

Alleles↗

PubMed2006

ClpS is an essential component of the N-end rule pathway in Escherichia coli.

The N-end rule states that the half-life of a protein is determined by the nature of its amino-terminal residue. Eukaryotes and prokaryotes use N-terminal destabilizing residues as a signal to target proteins for degradation by the N-end rule pathway. In eukaryotes an E3 ligase, N-recognin, recognizes N-end rule substrates and mediates their ubiquitination and degradation by the proteasome. In Escherichia coli, N-end rule substrates are degraded by the AAA + chaperone ClpA in complex with the ClpP peptidase (ClpAP). Little is known of the molecular mechanism by which N-end rule substrates are initially selected for proteolysis. Here we report that the ClpAP-specific adaptor, ClpS, is essential for degradation of N-end rule substrates by ClpAP in bacteria. ClpS binds directly to N-terminal destabilizing residues through its substrate-binding site distal to the ClpS-ClpA interface, and targets these substrates to ClpAP for degradation. Degradation by the N-end rule pathway is more complex than anticipated and several other features are involved, including a net positive charge near the N terminus and an unstructured region between the N-terminal signal and the folded protein substrate. Through interaction with this signal, ClpS converts the ClpAP machine into a protease with exquisitely defined specificity, ideally suited to regulatory proteolysis.

Amino Acid Sequence↗

PubMed2006

Lack of association of lobar intracerebral hemorrhage with apolipoprotein E genotype in an unselected population.

BACKGROUND: Both the upsilon2 and upsilon4 alleles of the apolipoprotein E gene (APOE) have been reported to be overrepresented in lobar intracerebral hemorrhage and to be associated with cerebral amyloid angiopathy (CAA). These studies were performed primarily on the North American population and investigated in partly selected patient cohorts. METHODS: 193 consecutive patients suffering from primary intracerebral hemorrhage (ICH) were included in our study. The localization of the ICH, i.e. cortico-subcortical, deep white matter, basal ganglia, brainstem and cerebellum, was put in relation to the APOE genotype and vascular risk factors. In 101 of these patients, the APOE genotype was also correlated to the presence and distribution of microbleeds and other microangiopathy-related damage, as shown by magnetic resonance imaging (MRI). RESULTS: We found neither an association of a specific APOE genotype with ICH localization nor with microangiopathy-related MRI findings. CONCLUSIONS: In our study of an unselected Central European population, the APOE genotype was not confirmed as a candidate for providing additional diagnostic and potentially prognostic information in patients with ICH.

Aged↗

PubMed2006

[Carbon monoxide--poison or potential therapeutic?].

Carbon monoxide (CO) is much more than just a toxic gas. Carbon monoxide is produced endogenously by the enzyme heme oxygenase and has important functions under physiological and pathophysiological conditions. Recent studies suggested antioxidative, anti-inflammatory, antiproliferative, anti-apoptotic, and vasodilating characteristics. Regarding clinically-relevant diseases in anesthesiology and critical care medicine, such as adult respiratory distress syndrome (ARDS), sepsis, or during organ transplantation, cytoprotective properties have been demonstrated by low-dose CO in experimental models. In view of a potential CO application in future human studies, this review discusses what is known to date about CO as it relates to functional, protective and toxic aspects.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

[The influence of a controlled active motion splint on proprioception after anterior cruciate ligament plasty. A prospective randomized study].

BACKGROUND: A ruptured anterior cruciate ligament (ACL) leads to both mechanical and functional instability. Functional instability is caused by proprioceptive deficit. The aim of this study was to determine whether the proprioceptive deficit can be reduced by using a controlled active motion (CAM) splint postoperatively. PATIENTS AND METHODS: A total of 50 patients with ACL rupture were randomized into two groups. After ACL plasty the PT group received postoperative physiotherapy, while the CAM group were managed with a CAM splint and physiotherapy. Proprioceptive ability was measured with a passive angle-reproduction test. RESULTS: On the day of discharge 80% of the patients in the CAM group and 25% in the PT group had a reduced proprioceptive deficit. Overall the main measured value in the CAM group improved by 83.7%, but deteriorated by 39.3% in the PT group. There was no significant difference between the CAM group and a healthy control group. CONCLUSION: Using a CAM splint in addition to physiotherapy after ACL plasty in comparison to physiotherapy alone decreases the proprioceptive deficit significantly. We recommend the use of a CAM splint in the postoperative management following ACL plasty.

Anterior Cruciate Ligament↗

PubMed2006

[A symptom oriented diagnostic approach to the workup of secondary forms of uveitis -- an internet based program for better and easier orientation in differential diagnosis].

BACKGROUND: The long list of ophthalmologic findings and symptoms at a baseline examination of a patient with uveitis can have an impact on further laboratory workup and differential diagnosis. METHODS: Based on publications and previous work, a decision tree was transformed into the expert system shell D3. A web-based Java Servlet was then programmed and published on our website (http://www.uveitiscenter.de at DiagnoseFinder). Ophthalmologic findings and symptoms of the patient can be checked with this online questionnaire, and recommendations for further laboratory tests and further care of the patient received. RESULTS: Retrospective analysis of 62 patients with characteristic features of secondary uveitis showed a good correlation between the actual diagnosis of the patient and the diagnosis found by the program. In 74% of cases, the correct diagnosis was found among other options. In 37%, only the correct diagnosis was found, while in 37% the correct diagnosis was found among other probable diagnoses. Not all forms of secondary uveitis were found easily by the software. CONCLUSION: This program is meant to be an easily accessible and simply employable help for the care of patients with a secondary form of uveitis. It is intended to be a support not only for residents in particular, but also for ophthalmologists in private practice who rarely treat patients with uveitis.

Decision Making, Computer-Assisted↗

PubMed2006

[Open intraperitoneal hernia repair for treatment of abdominal wall defects--early results by placement of a polypropylene-ePTFE-mesh].

BACKGROUND: Large incisional hernias are mainly repaired today by tension free implantations of prosthetic meshes using various placement methods. The advantages of the intraperitoneal open technique (IPOM) using a polypropylene mesh that is coated with ePTFE on the side facing the intestine, are described. METHODS AND RESULTS: 62 patients underwent an incisional hernia operation with the intraperitoneal positioning of a prosthetic mesh. The follow-up examinations after a range of 16.1 months showed a hernial recurrence rate of 6.4 %. A part of the resulting mesh infections (11.2 %) healed without surgical removal of the mesh. Clinical complications due to adhesion formation were not observed. CONCLUSION: The tissue sparing intraabdominal positioning technique simplifies the necessary overlap using healthy tissue as a prerequisite for a sufficient hernia repair exploiting the intraabdominal pressure.

Adult↗

PubMed2006

Type I interferon-associated skin recruitment of CXCR3+ lymphocytes in dermatomyositis.

BACKGROUND: Dermatomyositis (DM) is an autoimmune disease of unknown origin affecting skin and muscles. Infiltrating autoreactive T lymphocytes are thought to play an important pathogenetic role, but it is unclear which mechanisms are involved in the recruitment of these cells. Recent studies provided evidence that a type I interferon (IFN)-driven immune response, including the recruitment of T cells via IP10/CXCR3 interactions, might be important for the generation of skin lesions of cutaneous lupus erythematosus (CLE), an autoimmune disease that shares some clinical and histopathological features with DM. We hypothesized that a similar mechanism might also be involved in the pathogenesis of DM skin lesions. METHODS: Skin biopsies of 23 donors (11 DM, 5 healthy controls, 7 CLE controls) were analysed by immunohistochemistry using monoclonal antibodies against CD3, CD4, CD8, CD20, CD68, CD123, the chemokine receptor CXCR3 and its ligand IP10/CXCL10, and the myxovirus-resistance protein A (MxA)-protein, which is a specific marker for type I IFNs. RESULTS: We detected strong expression of the MxA protein in all DM skin biopsies, indicating involvement of type I IFNs. Expression of MxA was closely associated with expression of the interferon-inducible protein IP10/CXCL10 and the recruitment of CXCR3+ lymphocytes. Plasmacytoid dendritic cells appear to be an important source of type I IFNs in DM. DISCUSSION: Our results support the hypothesis that lesional type I IFN signalling, induction of IP10 expression, and recruitment of potentially autoreactive T cells via IP10/CXCR3 interaction are involved in the pathogenesis of DM skin lesions.

Adult↗

PubMed2006

Comparison of I5M and 4Pi-microscopy.

The axial (z-) resolution of approximately 100 nm provided by 4Pi and I5M fluorescence microscopy relies on the coherent addition of spherical wavefronts of two opposing high aperture angle lenses. Both microscopes feature a point-spread function (PSF) with a sharp central spot that is accompanied by axially shifted sidelobes which leads to replication artefacts in the raw image data. In a 4Pi-microscope the sidelobes are less pronounced than in I5M and without relevant lateral (x,y) substructure, making their posterior removal in the image reliable and fast. On the other hand, high speeds of raw data acquisition are more easily gained by I5M. Moreover, I5M features a stronger signal as compared to the commonly employed two-photon excitation (2PE) 4Pi-imaging mode. We investigate here the capability of both techniques to image (aqueous) specimens without artefacts. To this end, we consider the optical transfer function (OTF) of the two microscopes in conjunction with the signal-to-noise-ratio (SNR) of the object to be imaged. The imaging of E. coli bacteria with an interconvertable setup enabled a direct comparison of the two imaging modes. As both systems rely on high aperture angles, water-immersion lenses of the largest numerical aperture available (NA = 1.2) were employed. The experimental results are corroborated by simulations assuming the signal strength encountered in the experiment. The comparison of the theoretical with the experimental PSFs/OTFs showed that our setup operated close to theory in both imaging modes. Although I5M provided about 10 times brighter raw image data as compared to (2PE) 4Pi-microscopy, the I5M data could not be entirely cleared of artefacts. In conclusion, with the current aperture angles and fluorescence signal strengths, it is not advisable to trade in the suppression of the sidelobes for a larger image signal.

Artifacts↗

PubMed2006

Surfactant protein levels in bronchoalveolar lavage after segmental allergen challenge in patients with asthma.

BACKGROUND: Allergic asthma is associated with airway inflammation and dysfunction of pulmonary surfactant. Because surfactant proteins (SP) account for immunomodulatory functions as well as biophysical functions, we hypothesized that the allergic response in asthma might be accompanied by a dysregulation of SPs. METHODS: We measured levels of SP-A, SP-B, SP-C and SP-D by enzyme-linked immunosorbent assay in bronchoalveolar lavage (BAL) fluid of 23 asthma patients and 10 healthy control subjects under well-controlled conditions before and 24 h after segmental allergen provocation. These data were related to surfactant function, Th(2) cytokine levels in BAL fluid and to the degree of eosinophilic inflammation. RESULTS: In patients with asthma, allergen challenge increased BAL levels of SP-B, SP-C and SP-D while SP-A was decreased. For SP-B and SP-D, a moderate increase was also observed after saline challenge. In contrast, no alterations were observed in healthy control subjects. Levels of SP-B and SP-C in asthmatics correlated with the ratio of small to large surfactant aggregates (SA/LA ratio) and correlated negatively with BAL surface activity. Furthermore, increased SP-C but not SP-B levels after allergen challenge correlated with eosinophil numbers, interleukin (IL)-5, and IL-13 in BAL while increased SP-D levels only correlated with eosinophil numbers. CONCLUSIONS: This study demonstrates significant alterations of all SPs in BAL fluid after allergen challenge of which SP-C was most closely related to surfactant dysfunction and the degree of the allergic inflammation.

Adult↗