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Biomedical subjects

W I Steudel

Publications and source records attributed to W I Steudel.

At least 19 recordsLinked to original sources

Histochemical alterations of re-innervated rat extensor digitorum longus muscle after end-to-end or graft repair: a comparative histomorphological study.

Changes in the histochemical profile of 43 rat extensor digitorum longus muscles undergoing de-innervation and re-innervation were recorded. Assessment of fibre type composition and muscle fibre cross-sectional area was performed at 15, 30, 90 and 180 days post operative (p.o.) after either primary end-to-end repair or autologous graft repair of the common peroneal nerve (n = 5 per time point and type of repair). The size and histochemical profile of single muscle fibres were analysed by computer-assisted quantification on the basis of their myofibrillar ATPase (pH 4.3) and succinate dehydrogenase (SDH) activities in serial, whole-muscle cross-sections. Accordingly, four muscle-fibre types could be functionally identified: (1) slow oxidative (SO, type I); (2) fast-oxidative glycolytic (FOG, type IIA); (3) fast glycolytic (FG, type IIB); and (4) succinate dehydrogenase intermediate (SDH-INT). At 15 days following end-to-end repair, the SDH-INT muscle fibre type was observed. By contrast, 15 days following graft repair, no changes in fibre type composition were observed (vs. control). At 30 days p.o. in the group that received end-to-end repair, type SDH-INT reached its maximum and was significantly higher than in the group that underwent graft repair. At 90 days p.o., the amount of SDH-INT fibres declined after end-to-end repair, but it was still significantly higher than in the group treated with a nerve graft. The increase of the SDH-INT fibre type was mirrored by a proportional disappearance of FG and FOG fibres. These changes were time-dependent, not reversible at 180 days p.o and largely blunted after nerve graft. Muscle-fibre size decreased at 15 and 30 days after both types of nerve repair. This decrease was transient and reversible within 90 days p.o. These findings reflect the fact that the reorganization of the histochemical profile in re-innervated muscles is both time dependent and long lasting. The degree of this reorganization is significantly higher after end-to-end repair than after graft repair.

Adenosine Triphosphatases↗

[A grading system for chronic hydrocephalus].

A generally accepted grading system for patients suffering from chronic hydrocephalus has not been established yet. Therefore we designed a new grading system, which focuses on five symptom categories: gait disturbances, mental disorder, incontinence, headache, dizziness. For each category clearly circumscribed degrees of handicaps are defined. For each degree a value between 0-6 points is assigned in concordance to the severity of handicap. To get a generally accepted validation of the obstruction, the assigned values were oriented on the values provided in Germany to evaluate the degree of obstruction for insurances.[nl]In contrast to the established gradings of Stein and Langfitt and the Black Rating Scale our grading allows a more exact acquisition of the clinical presentation of a patient. Our experiences with the grading seemingly indicate also, that it is reliable. Because the grading allows an incorporation of measurable data such as psychometric analysis or gait analysis, our grading is useful as well for everydays' practice as for scientific purpose.

Chronic Disease↗

Screw fixation to the posterior cortical shell does not influence peak torque and pullout in anterior cervical plating.

There is no consensus over whether screw fixation for anterior cervical plating should include the posterior cortical shell of the vertebral bodies or not. Thus, the purpose of this study was to investigate the function of the posterior cortical shell with respect to maximal screw torque and pullout force. Twenty-four fresh frozen human cervical vertebrae coming from six spinal segments C4-C7 were used. They were scanned for bone mineral density (BMD) and then assigned to two groups with comparable bone density and segmental distribution. The posterior longitudinal ligament was resected carefully and two parallel burr holes were drilled into each vertebral body. The posterior cortical shell was removed in one burr hole, using a 6-mm steel burr, producing a shallow excavation with a depth of approximately 2 mm. An ABC screw was inserted into each burr hole. The screw to be inserted into the hole with the posterior excavation was called "monocortical". In contrast, the contralateral screw was called "bicortical". Peak torque was measured in one group, while pullout force was analyzed using the specimens of the second group. Mean value and standard deviation were calculated for peak torque and pullout force with respect to the type of fixation. A paired t-test was used to determine the effect of fixation type on peak torque and pullout force. Pearson moment correlation coefficients were calculated to determine the effect of BMD on peak torque and pullout force with respect to whether the screw was "mono- or bicortical". A 95% level of significance was used for all tests. No significant differences for peak torque and pullout force could be found comparing monocortical and bicortical screw fixation. However, for both monocortical and bicortical screw fixation, a positive correlation was seen for peak torque versus BMD and for pullout force versus bone mineral density, respectively. The importance of the posterior cortical shell for screw pullout force and screw peak torque seems to be negligible. In constrast, BMD greatly influences both peak torque and pullout force for both types of fixation.

Bone Density↗

Online analysis of intracranial pressure waves.

Brain pressure waves, particularly B-waves, as they were described by Lundberg contain valuable diagnostic information about the patient's status. So far, this information cannot be used on a daily routine basis because manual analysis of the recorded ICP data is very time consuming. Furthermore, the analysis is only retrospective, after incidents of interest occurred. To overcome these drawbacks, an automated B-wave detection system has been developed. Using a direct spectral estimation method (so called ARMA approach) the most significant spectral components and their amplitudes in the ICP signal are identified. The frequency with the biggest amplitude inside the B-wave band is a reliable indicator of B-wave activity and can be displayed on-line on a bedside computer.

Humans↗

[Modern intracranial pressure measurement techniques. Basic principles and general practice].

Measurement of intracranial pressure (ICP) has to be regarded as a standard procedure in today's treatment of severe head-injured patients. Intraventricular or intraparenchymal measurement should be used. The essential value for intensive care treatment is the cerebral perfusion pressure (CPP). Its value should be kept strictly > 70 mmHg. Computer-based analysis of the ICP-signal provides further options of an online monitoring of intracranial reserve capacity and the state of autoregulation. However, until now, there are no software solutions commercially available which would allow for such advanced signal analysis--the reason might be that the potential of advanced signal analysis has only been discovered within the recent years.

Adult↗

[LOVA hydrocephalus - a new entity of chronic hydrocephalus].

The recently defined term "longstanding overt ventriculomegaly in adults" (LOVA) describes a unique entity of chronic occlusive hydrocephalus. The experiences so far using conventional DP valves were not encouraging because of a high percentage of overdrainage. The objective was to evaluate whether gravitational shunts could be used for this condition with an acceptable overdrainage risk. Twenty-three macrocephalic adults aged 17-72 years suffered from chronic progressive hydrocephalic conditions. They received two different types of gravitational shunt. Follow-up ranged from 6 months to 75 months. Only two patients presented small subdural effusions postoperatively, and only one required additional treatment for that. Eighty-two percent were shunt responders. Ventricular size was only marginally reduced in 22 of the 23 patients. There was no correlation between clinical benefit and the reduction in ventricular size. Gravitational shunts clearly have the potency for safe treatment of LOVA, significantly reducing the risk of overdrainage over conventional valves, and may be considered an equivalent alternative to third ventriculostomy.

Adult↗

PHF3-specific antibody responses in over 60% of patients with glioblastoma multiforme.

Glioblastoma multiforme (GBM), a malignant astrocytic tumour, represents the most frequent tumour of the human brain. Nevertheless, its molecular pathology is not well understood. We utilized the immune system, which contributes to cancer protection, to help identify new GBM-related genes. By screening a human GBM cDNA library with autologous patient serum (SEREX-approach), we isolated a gene termed PHF3 (PHD finger protein 3). The gene product of PHF3 is immunogenic in GBM as tested in an allogenic patient serum screening demonstrating antibodies in 24 of 39 (61.53%) sera, whereas none of the 14 healthy persons had antibodies against PHF3. While previous SEREX studies revealed allogenic antibody responses up to 40%, our results for PHF3 represent the highest reported rate for a specific antibody response. We show that GBM patients with an antibody response against PHF3 show significant better survival than patients without PHF3-specific antibodies. Because the amino acid sequence of PHF3 contains a PHD finger (also termed LAP motif), a TFIIS homology, a proline rich region and nuclear localization signals, it supposedly functions as a transcription factor. A polyclonal antibody generated against PHF3 shows nuclear expression in most investigated formalin-fixed, paraffin embedded tissues. In GBM, PHF3 expression is concentrated in cells surrounding necroses.

Adult↗

KUB3 amplification and overexpression in human gliomas.

Gene amplification is known to occur frequently in human glioma. Recently we reported cloning of a novel gene termed glioma-amplified sequence 16 (GAS16) by microdissection-mediated cDNA capture. In this article, we demonstrate that GAS16 results from an alternative splicing process of the Ku70 binding protein 3 (KUB3) that is essential for DNA double-strand break repair. The alternative splice product was found in glioblastoma and in normal fetal brain. We determined the amplification frequency of KUB3 in glioma with different grading. We analyzed a total of 102 glioma primary tumors and found KUB3 to be amplified in 12/82 (14%) glioblastomas, 4/13 anaplastic astrocytomas (30%), and 2/4 astrocytomas, but in none of three pilocytic astrocytomas. Northern blot analysis of glioblastoma shows a strong correlation between KUB3 amplification and overexpression. Amplification of KUB3 appears to be independent of other genetic changes frequently associated with the development of gliomas, including EGFR amplification, LOH of TP53, and LOH of chromosome 10. The KUB3 amplification and overexpression may interfere with the function of KUB3 in the DNA-PK complex involved in the maintenance of genome stability and reduction of mutation frequency.

Alternative Splicing↗

Guidelines for guidelines.

Clinical practice guidelines (CPGs) are suited tools for controlling and improving the effectiveness and efficiency of medical care. With the upcoming internet, the numbers of CPGs have increased rapidly, however, only few offer the attributes of good guidelines such as reliability/reproducibility, applicability, flexibility, clarity, multidisciplinary process, scheduled review and documentation of clinical and scientific evidence. Nearly identical criteria for appraisal of CPGs have been developed in many countries consisting of a checklist with questions concerning the quality of development, the content and format, and the applicability of the guideline. In the United States, guidelines which successfully passed the appraisal (or clearing) process, were stored in the National Guideline Clearinghouse, an internet-based database. A German counterpart is under construction, which will comprise clearing reports reviewing and appraising all existent guidelines covering a medical topic. Developing high-quality CPGs is a time consuming and expensive process. A widely accepted guideline for guideline development was published by the Scottish Intercollegiate Guideline Network. CPGs touching neurosurgical topics are rare and often developed without neurosurgical participation. Due to the potential medico-economic impact of CPGs in the future, national neurosurgical societies and their international associations should play a more active role in the development and implementation of CPGs.

Evidence-Based Medicine↗

The influence of cancellous bone density on load sharing in human lumbar spine: a comparison between an intact and a surgically altered motion segment.

The aim of the current study is twofold: first, to compare load sharing in compression between an intact and a surgically repaired lumbar spine motion segment L3/4 using a biomechanically validated finite element approach; second, to analyse the influence of bone mineral density on load sharing. Six cadaveric human lumbar spine segments (three segments L2/3 and three segments L4/5) were taken from fresh human cadavers. The intact segments were tested under axial compression of 600 N, first without preload and then following instrumented stabilisation. These results were compared to a finite element model simulating the effect of identical force on the intact segments and the segments with constructs. The predictions of both the intact and the surgically altered finite element model were always within one standard deviation of the mean stiffness as analysed by the biomechanical study. Thus, the finite element model was used to analyse load sharing under compression in an intact and a surgically repaired human lumbar spine segment model, using a variety of E moduli for cancellous bone of the vertebral bodies. In both the intact and the surgically altered model, 89% of the applied load passed through the vertebral bodies and the disc if an E modulus of 25 MPa was used for cancellous bone density. Using 10 MPa--representing soft, osteoporotic bone--this percentage decreased, but it increased using 100 MPa in both the intact and the altered segment. Thus, it is concluded that reconstruction of both the disc and the posterior elements with the implants used in the study recreates the ability of the spine to act as a load-sharing construction in compression. The similarity in load sharing between normal and instrumented spines appears to depend on assumed bone density, and it may also depend on applied load and loading history.

Biomechanical Phenomena↗

Alterations of norepinephrine levels in plasma and CSF of patients after traumatic brain injury in relation to disruption of the blood-brain barrier.

BACKGROUND: In injured brain tissue with a disrupted blood-brain barrier (BBB) catecholamines such as norepinephrine (NE) are known to enhance glucose consumption and cerebral blood flow but may lead to an energy depletion increasing the risk of ischemia. Therefore it is of great interest whether the exogenous administration of NE used mainly to maintain an adequate cerebral perfusion pressure influences CSF NE levels or not, and whether elevated plasma or CSF levels of NE can influence the actual clinical condition. We addressed this issue by measuring the levels of NE in CSF and plasma and correlating them with the actual clinical condition of the patients. METHODS: In 29 patients with severe TBI (< 8 points on the Glasgow Coma Scale, GCS) NE levels were analysed by high performance liquid chromatography (HPLC) in paired blood and CSF specimens which were collected from days 1 to 14 after severe TBI (total number of pairs = 121). The integrity of the BBB was evaluated by determining the CSF/serum albumin ratio. The clinical condition of the patients was assessed by GCS. RESULTS: Elevated plasma and CSF NE levels were observed in 50% of all samples, most consistently in patients treated with NE. NE elevation in CSF was independent of whether or not the BBB remained intact. There was no correlation between GCS and the levls of NE in CSF or plasma either in samples from the treated or the untreated group. INTERPRETATION: Exogenous administration of NE seems to increase NE levels in plasma and CSF. However, in this group of patients with severe TBI there was no clinical evidence that exogenous administration of NE was detrimental to the traumatized patients.

Adolescent↗

Glioma-expressed antigen 2 (GLEA2): a novel protein that can elicit immune responses in glioblastoma patients and some controls.

Glioma constitutes the most frequent brain tumour in man with glioblastoma as the most prevalent and malignant type. The average survival time of less than 16 months underlines the need for improvements in diagnosis and therapy. Here, we report the identification of a novel antigen termed glioma-expressed antigen 2 (GLEA2) causing a frequent immune response in glioma patients. Screening of 450 000 clones from a glioblastoma lambda zap expression library with autologous patient serum revealed a group of five serum-positive clones sharing a high sequence homology. Further sequence analysis showed a sequence homology to a hepatocellular carcinoma associated antigen 58 (HCA58). We localized the novel HCA homologous gene termed glioma-expressed antigen 2 (GLEA2) on chromosome 20 by somatic cell hybrid panel mapping. Using allogenic sera from 39 glioblastoma patients, we found an immune response against GLEA2 in 17 patients (43%). In addition, screening with allogenic sera from other glioma patients revealed GLEA2 directed antibodies in two out of five pilocytic astrocytomas and in one out of two astrocytomas. Unrelated tumour sera revealed no immune response and sera from healthy persons showed an immune response in two out of 14 cases (14%). Northern blot hybridization and RT-PCR showed ubiquitous GLEA2 gene expression in glioma and normal tissues. The novel HCA homologous gene, GLEA2, appears to induce a frequent immune response in glioma. In the light of the lack of useful glioma markers, it appears reasonable to consider GLEA2 as a potential future diagnostic marker.

Amino Acid Sequence↗

Ultrasound-guided aspiration of brain abscesses through a single burr hole.

Surgical aspiration and/or drainage of brain abscesses is considered to be the first-line treatment for abscesses larger than 25 mm. This is ususally performed with the aid of CT-guided stereotaxy. A method of ultrasound guidance is presented that allows a single burr hole approach with real-time imaging of the whole procedure. A bayonet-like shaped ultrasound probe with tip dimension of 8 x 8 mm only (EUP-NS 32, Hitachi/Ecoscan) with frequencies of 3.5 and 5 MHz is used. After placement of a burr hole the target is identified by transdural insonation, a guideline is adjusted and a mounted puncture-adapter guides the cannula towards the lesion under real-time imaging control. Up to now 12 abscesses in 10 patients were treated. Visualization was always excellent. A second aspiration had to be performed twice. One abscess did not contain enough pus to be cured by aspiration and was removed by open surgery, another could not be tapped by the blunt cannula and was aspirated under stereotactic control using a sharp trocar. Outcome was excellent in 6 patients and fair in 2 patients but this was due to the pre-existing disease. Two patients admitted in deep coma died despite an emergency operation. The presented method has proven to be a very powerful guiding tool in the surgical treatment of brain abscesses through a single burr hole approach.

Adolescent↗

Differential release of interleukines 6, 8, and 10 in cerebrospinal fluid and plasma after traumatic brain injury.

Traumatic brain injury (TBI) is characterized by a high mortality which is largely determined by the initial cerebral trauma, secondary brain injury or indirectly during a Multiple Organ Dysfunction Syndrome (MODS). Therefore, we analyzed IL-6, IL-8, and IL-10 in cerebrospinal fluid (CSF) and in plasma with respect to blood-brain barrier (BBB) integrity in 29 patients suffering from isolated TBI. IL-6 and IL-8 were significantly increased compared to baseline levels early after trauma in CSF and plasma. In all patients CSF IL-6 and IL-8 were found to be higher than corresponding plasma levels. IL-10 in plasma was significantly increased above control plasma values, however, without a significant difference to the corresponding CSF values. BBB dysfunction was temporary present in 23 patients. Significant correlations between BBB dysfunction and cytokines were not found. Thus, alterations of the BBB seems not to influence the distribution pattern of interleukines in CSF and plasma after trauma.

Adolescent↗

PHF3 expression is frequently reduced in glioma.

Glioblastoma is the most frequent brain tumor and accounts for approximately 50--60% of all astrocytic tumors. Many chromosome alterations have been described in glioblastoma, but only for a few alterations were the genes identified and linked to genetic pathways in glioblastoma development. To contribute to the identification of novel genes involved in glioblastoma development we used a combined immunological and molecular screening approach. Here we report the identification and expression analysis of a novel gene from human chromosome 6q12 that is considered to be the third member of a family of PHD finger containing genes and is termed PHF3. PHF3 is ubiquitously expressed in normal tissues including brain, but its expression is significantly reduced or lost in glioblastoma, glioblastoma cell lines, anaplastic astrocytomas and astrocytomas. The PHF3 protein sequence contains several protein motifs frequently found in transcription factors. One of those motifs is a PHD finger, also termed LAP motif and known to bind large portions of DNA. Another region of the protein revealed a high homology to the transcription factor TFIIS, especially to a region that is necessary for the Polymerase II binding properties of TFIIS. Combining these results, PHF3 is a novel member of a large class of regulatory proteins containing a LAP motif, and loss of its expression in glioblastoma may contribute to glioma development.

Adult↗

Vertex epidural hematoma with communicating bifrontal subgaleal hematomas treated by percutaneous needle aspiration.

The case of an 11-year-old boy is presented who suffered a bicycle accident with a parasagittal skull fracture, a small vertex epidural hematoma, frontal contusions and a frontal subgaleal hematoma. Enlargement of the vertex epidural hematoma was diagnosed after development of a slight paraparesis on day 11 with the aid of MRI. Three percutaneous needle aspirations of the subgaleal hematoma with a total of 59 ml being evacuated led to quick recovery and disappearance of the subgaleal as well as the vertex epidural hematoma. It is speculated that both hematomas communicated via the skull fracture thus making the evacuation of the epidural hematoma by subgaleal punctures possible.

Brain Injuries↗

Changes in regional energy metabolism after closed head injury in the rat.

We examined in the present investigation regional ATP, glucose, and lactate content in the cortical and subcortical structures, in a rat model of closed head injury (CHI). In serial tissue sections bioluminescence imaging of ATP, glucose, and lactate was performed at 4 h, 12 h and 24 h (n = 4/5 per time point with) after the induction of CHI or sham surgery. Bioluminescence images were analyzed by computer-assisted densitometry, at the lesion site, in remote cortical areas, and in the subcortical structures (thalamus and caudate nucleus). ATP content was significantly decreased at the lesion site after 4 h and in the remote cortex at 12 h post-injury. At 12 h, the ATP content reached baseline levels on the ipsilateral side and at 24 h also at remote lateral parietal sites. In the contralateral cortex, ATP increased transiently above the baseline at 12 h. No significant changes in ATP were found in the thalamus and caudate nucleus. Cortical glucose and lactate contents could not be discerned over time. Following CHI there is an acute and progressive, yet transient, ischemic cortical profile, which is not reflected in subcortical areas.

Adenosine Triphosphate↗