Search PubMed⌕ Search

Biomedical subjects

U Schlegel

Publications and source records attributed to U Schlegel.

At least 19 recordsLinked to original sources
PubMed2006

Methionine metabolism and phenotypic variability in X-linked adrenoleukodystrophy.

A combined genotype of polymorphisms of methionine metabolism has been associated with CNS demyelination in methotrexate-treated patients. Within a sample of 86 patients with X-linked adrenoleukodystrophy, this genotype was overrepresented in a subgroup of 15 patients with adrenomyeloneuropathy (AMN) with CNS demyelination (adrenoleukomyeloneuropathy) in comparison to 49 AMN patients without CNS demyelination ("pure" AMN; p = 0.002), suggesting that methionine metabolism might contribute to the phenotypic variability in adrenoleukodystrophy.

Adolescent↗
PubMed2006

[NeuroCogFX--a computer-based neuropsychological assessment battery for the follow-up examination of neurological patients].

Many neurological therapeutic trials require a longitudinal assessment of cognitive functions. An ideal instrument for that purpose should be in accordance to the criteria of classical testing theory and, furthermore, it should be repeatable and economic in administration and interpretation. We developed NeuroCogFX, a computerized assessment battery, according to these criteria. NeuroCogFX comprises subtests for short term memory, working memory, psychomotor speed, selective attention, verbal and figural memory and verbal fluency (mean duration: 25 minutes). Age-related normative data was obtained from 244 subjects without history of neurological or psychiatric disease (age range 16 - 75 years). Forty-two subjects were re-tested after an average of 8 weeks (range: 6 - 10 weeks) in order to assess retest reliability and training effects. Retest-reliabilities were middle-sized in all but one subtest, ranging from r (12) = 0.5 to r (12) = 0.7 (2-back Test: r (12) = 0.37). For construct validation NeuroCogFX was administered in addition to a comprehensive neuropsychological assessment battery in a group of 40 healthy subjects and in 42 patients with chronic epilepsy. The test allows a valid assessment of short-term memory, reaction speed, memory and verbal fluency. NeuroCogFX is an economic, sufficiently reliable and valid instrument for the neuropsychological follow-up examination in single patients and study groups which can be administered if a comprehensive neuropsychological assessment is unavailable.

Adolescent↗
PubMed2006

Low-grade gliomas -- current concepts.

Diffuse astrocytomas, oligodendrogliomas, and oligoastrocytomas (mixed gliomas) WHO grade II, pleomorphic xanthoastrocytomas (PXAs), pilocytic astrocytomas, and subependymal giant cell astrocytomas (SEGAs) are often referred to as low-grade gliomas. WHO grade II astrocytomas, oligodendrogliomas, and mixed gliomas are characterized by their infiltrative growth, frequent tumor recurrence and a more than 50 % risk for malignant progression. In contrast, pilocytic astrocytomas and SEGAs are circumscribed tumors amenable to a (radio)surgical cure. There are few universally accepted guidelines for the treatment of low-grade gliomas. In this review, three neurosurgeons, a neurologist, a neuropathologist, and a radiation oncologist discuss some of the difficult issues surrounding the diagnosis and treatment of low-grade gliomas from their individual points of view (i. e., classification and neuropathology, MR imaging, stereotactic biopsy, microsurgery, interstitial radiotherapy/brachytherapy, radiotherapy, wait and see strategy).

Brain Neoplasms↗
PubMed2005

FDG-PET in immunocompetent patients with primary central nervous system lymphoma: correlation with MRI and clinical follow-up.

PURPOSE: The role of FDG-PET in primary central nervous system lymphoma (PCNSL) is unclear. It was the aim of this study to investigate the role of FDG-PET in detecting PCNSL and in predicting response to chemotherapy. METHODS: An FDG-PET scan of the brain was performed in 15 patients with histologically proven PCNSL (16 PET examinations, Siemens ECAT EXACT). PET was planned to investigate patients at the time of primary diagnosis, after chemotherapy and at the time of suspected relapse in seven, five and three cases, respectively. All except two patients simultaneously underwent MRI of the brain. FDG-PET results were correlated with histological results after stereotactic biopsy (primary diagnosis group) and with clinical data and MRI during follow-up. RESULTS: Six of the seven patients in the primary diagnosis group demonstrated a true positive finding (86%). In one of the true positive PET patients, there were two tumour lesions, one of which was only detectable on the FLAIR MRI sequence. In five patients, FDG-PET showed no sign of PCNSL during ongoing chemotherapy. These results were confirmed by the clinical follow-up (mean 26.6 months). MRI demonstrated minimal residual disease which had disappeared on further follow-up MRI in three of these five patients at the time of PET scanning. Recurrence of disease was confirmed concordantly by FDG-PET and MRI in three different patients. The standardised uptake value of all tumours was 10.2 (4.3-13.7). CONCLUSION: PCNSLs demonstrate high FDG uptake and can be diagnosed by FDG-PET with high sensitivity. It seems that FDG-PET is suitable for early therapeutic monitoring after chemotherapy.

Aged↗
PubMed2005

Neuropsychological outcome after chemotherapy for primary CNS lymphoma: a prospective study.

BACKGROUND: Combined radio- and chemotherapy for primary CNS lymphoma (PCNSL) is associated with a considerable risk of long-term neurotoxicity. The impact of high-dose methotrexate (MTX)-based chemotherapy alone on cognition and quality of life (QOL) is controversial. OBJECTIVE: To assess the impact of the tumor itself and its treatment with high-dose MTX-based chemotherapy on long-term cognition and QOL in patients with PCNSL. METHODS: Prospective neuropsychological examinations and MRI were performed in patients with PCNSL who were in complete remission for more than 12 months after completion of chemotherapy. A QOL assessment was performed at long-term follow-up. RESULTS: Twenty-three patients were eligible. The median follow-up period was 44 months after diagnosis. In long-term follow-up, 22 (95%) of 23 patients showed either preserved or improved cognitive functions as compared with pretreatment and immediate posttreatment baseline assessment. One patient showed an isolated decline in psychomotor speed. Eleven (48%) of 23 patients displayed at least mild cognitive deficits at long-term follow-up not related to therapy. Nineteen (83%) of 23 patients reported a good QOL. MRI revealed confluent white matter abnormalities in eight patients that were not associated with cognitive decline. CONCLUSION: In patients with primary CNS lymphoma (PCNSL) treated with a methotrexate (MTX)-based chemotherapy, no gross cognitive decline has to be expected as a long-term treatment effect. MTX-induced white matter changes apparent on MRI are not inevitably associated with cognitive impairment. Nevertheless, a substantial fraction of patients with PCNSL retain cognitive deficits as a residual symptom of the tumor.

Adult↗
PubMed2005

MTX-induced white matter changes are associated with polymorphisms of methionine metabolism.

Methotrexate (MTX) is a folate antagonist inhibiting nucleic acid and methionine synthesis. Methionine is necessary for CNS myelination. In 42 patients with primary CNS lymphoma (PCNSL) treated with a systemic and intraventricular high-dose MTX-based polychemotherapy, the presence of a risk haplotype defined by polymorphisms influencing methionine metabolism referred a relative risk for CNS white matter changes of 4.7 (p = 0.001). The authors conclude that methionine metabolism influences MTX neurotoxicity.

Aged↗
PubMed2005

Infection resistance of unreamed solid, hollow slotted and cannulated intramedullary nails: an in-vivo experimental comparison.

Infection continues to be a problematic complication of fracture treatment, particularly in severe open fractures. The implant design and material as well as implantation technique play an important role in the pathogenesis of local infection. The aim of our study was to determine if the local resistance to infection of a cannulated IM nail is less than that of a solid nail and more similar to that of a hollow nail. In 65 female White Zealand rabbits, the intramedullary cavity was inoculated with matching concentrations of Staphylococcus aureus, and one of the three nails was inserted. The solid nail had a greater than twofold higher resistance to infection (23%) compared to that of the other two nails (hollow, 65%; cannulated, 61%) which was statistically significant (p<0.02). No difference in infection resistance was detected between the hollow slotted and cannulated nail designs (p=1). Although these experimental results may be clinically considered, direct extrapolation to clinical infection rates is ill advised.

Animals↗
PubMed2005

[Acute central nervous symptoms in oncologic patients].

Oncologic patients may suffer from acute central nervous system disorders either related to the disease itself or to its therapy. These disorders may present as a disturbance of consciousness, as mental changes, as focal neurological signs, as epileptic seizures or as a combination of these. Symptoms may be caused by cerebral metastases, hemorrhage, ischemia or infectious complication, by metabolic changes or by treatment sequealae. This article will focus on clinical presentation, diagnostic workup and possible therapy or prophylaxis of these complications.

Acute Disease↗
PubMed2005

[Is computer navigation a useful tool in unicompartmental knee arthroplasty? A pilot cadaver study].

We conducted this pilot cadaver study to investigate whether the use of a navigation system during minimally invasive unicompartmental knee arthroplasty leads to more consistent results than the conventional hand-guided technique. We describe the accuracy of implant positioning in using standard instrumentation and computer navigation. Radiographic assessment showed that accurate component placement was achieved using both methods. These results were not statistically significant. The computer navigated femoral component placement without intramedullary (IM) rod was as accurate as the conventional method with IM rod. The study showed that computer navigation can produce accurate results even without an intramedullary rod. Image guidance can maintain the accuracy of the standard instrumentation and enhance 3D vision and the intraoperative orientation of the surgeon.

Arthroplasty, Replacement, Knee↗
PubMed2004

Clonal evolution as pathogenetic mechanism in relapse of primary CNS lymphoma.

Comparative investigation of immunoglobulin (Ig) heavy chain gene rearrangements and DNA sequence analyses of a primary lymphoma of the CNS (PCNSL) and its recurrence revealed that both tumors used the same Ig gene segment. In addition to shared somatic mutations, the primary and the recurrent PCNSLs harbored somatic mutations unique to each tumor. Clonal evolution rather than subclone selection appears to underlie the development of tumor recurrence in this case.

Aged↗
PubMed2004

The methionine synthase polymorphism D919G alters susceptibility to primary central nervous system lymphoma.

Primary central nervous system lymphomas (PCNSL) frequently reveal genomic instability. We analysed different functional genetic variants affecting the folate and homocysteine metabolism important for DNA integrity in 31 PCNSL patients and 142 controls. We found significantly less carriers of the methionine synthase c.2756A>G (D919G) missense polymorphism among the patients (0.16 vs 0.42; odds ratio 0.26, CI(95%): 0.09-0.74; P=0.005), suggesting a protective function of the G allele. These data stimulate further epidemiological and functional studies focusing on the role of homocysteine and folate metabolism in lymphoma tumorigenesis.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2004

[Influence of local application of basic fibroblast growth factor on resistance to local infection after standardized closed soft tissue trauma. An experimental study in rats].

The aim of the study was to obtain information on the importance/influence of local application of an angiogenic potent growth factor (bFGF) on local infection resistance after soft tissue trauma.A paired comparison of infection rates was carried out on Sprague-Dawley rats after standardized, closed soft tissue trauma and local, percutaneous bacterial inoculation of different concentrations (2 x 10(4)-2 x 10(7)), whereby the lower leg was treated with 1, 10, and 100 ng bFGF (n=16 each) and without bFGF (n=16). Statistical evaluation of the differences between the infection rates of both groups was performed using the two-sided Fisher's exact test ( p<0.05). For the group without bFGF application, the infection rate was 25%. In the groups with 1, 10, and 100 ng bFGF application, the infection rates were 50%, 69%, and 81%. The difference in the infection rates for the groups in which 10 and 100 ng bFGF were applied was highly significant ( p=0.032/ p=0.004) compared with the group without bFGF. If these initial results are confirmed for other angiogenic potent growth factors, then the local application of growth factors to stimulate wound and bone healing will need to be reconsidered and preceded by a very strict evaluation of the risks and benefits.

Animals↗
PubMed2004

[Animal models of osteomyelitis].

Despite new approaches in biochemical testing, radiologic and nuclear medicine and advances in surgical techniques, the problem of diagnosis and therapy of acute and chronic osteitis has not been finally solved. Clinical research on osteitis is problematic as there are many variables influencing the inflammatory process and a wide spectrum in therapeutic options exists, hampering research under defined conditions. Consequently, there was an early need for animal models. In vivo experimental settings were established to gain reproducible and reliable results under standardized conditions on the pathogenesis and therapy of osteitis. In this article, an overview of the hitherto established experimental animal models and the results of osteitis research on these models is given.

Animals↗
PubMed2004

The influence of cyclic compression and distraction on the healing of experimental tibial fractures.

Interfragmentary displacement has a main effect on callus formation in fracture healing. To test whether compressive or distractive displacements have a more pronounced effect on new bone formation, a sheep osteotomy model was created whereby the gap tissue was subjected to constant bending displacement. A diaphyseal osteotomy with a gap of 2 mm was created in 18 sheep tibiae and stabilized with a special unilateral actuator-driven external fixator. Two experimental groups with six sheep each received either 10 or 1000 cycles evenly distributed over 24 h. The third group of six sheep served as a control group without actively induced displacement. The amount and direction of cyclic displacement was kept constant throughout the observation period, resulting in 50% compressive and 50% distractive displacement within the osteotomy gap. At sacrifice, six weeks after surgery, bending stiffness was measured and new bone formation was assessed radiologically and microradiographically. In all cycled groups, the amount of periosteal callus formation was up to 25 times greater on the compression compared to the distraction side (p < 0.001). The application of the higher number of daily cycles resulted in an up to 10-fold greater amount of periosteal new bone formation on the compression side (p < 0.012), while the difference on the distraction side was not significant. Ten cycles applied a day were sufficient to create an abundant periosteal callus on the compression side. In the 1000 cycle group, bending stiffness revealed slightly lower values but the difference was not significant. Solid periosteal bridging of the gap was observed in two sheep in the control group, whereas bridging in the cycled groups was observed exclusively at the medullary side. In conclusion, cyclic compressive displacements were found to be superior over distractive displacements. A higher number of enforced and maintained compressive displacements enhanced periosteal callus formation but did not allow bony bridging of the gap.

Animals↗
PubMed2003

Biomechanical evaluation of healing in a non-critical defect in a large animal model of osteoporosis.

Current methods for fracture treatment in osteoporosis are not always sufficient. To develop new fixation strategies (both mechanical and biological) requires pre-clinical testing utilizing appropriate models. The aim of this study was to apply a recently developed sheep model of osteoporosis to the study of healing in a non-critical long bone defect. A standardized transverse mid-shaft tibial osteotomy (with a fracture gap of 3 mm) was performed in seven osteoporotic and seven normal sheep and stabilized with a special external fixator for 8 weeks. The fixator was used for weekly in vivo bending stiffness measurements. Ex vivo bending stiffness and torsional stiffness of the callus zone were also determined. Callus area, callus density, and osteoporosis status were determined at 0, 4, and 8 weeks using peripheral quantitative computed tomography. The increase of in vivo bending stiffness of the callus was delayed approximately 2 weeks in osteoporotic animals. A significant difference (33%) in torsional stiffness was found between the osteotomized and contralateral intact tibia in osteoporotic animals, but no significant difference occurred in normal sheep (2%). In osteoporotic animals, ex vivo bending stiffness was reduced 21% (p=0.05). Bending stiffness was correlated with callus density (r=0.76, r=0.53); torsional stiffness was correlated with callus area (r=0.60) and to a lesser extent with callus density (r=0.53). This study demonstrated a delay of fracture healing in osteoporotic sheep tibiae with respect to callus formation, mineralization, and mechanical properties.

Animals↗
PubMed2003

Treatment of CNS lymphoma with the anti-CD20 antibody rituximab: experience with two cases and review of the literature.

Treatment with radio- and chemotherapy has become increasingly efficient in primary CNS lymphoma (PCNSL). However, time to tumor progression is often short, and the majority of patients eventually relapse. Therefore, new therapeutic modalities are needed. One possible new option is the use of monoclonal antibodies (moabs) such as the humanized anti-CD20 moab rituximab. Treatment with intravenous rituximab has resulted in response rates of 50% in systemic non-Hodgkin's lymphoma and was also efficient in PCNSL as well as in CNS involvement of systemic disease. However, rituximab concentrations in the cerebrospinal fluid are low after systemic application. Therefore, the authors performed an intraventricular rituximab treatment in 2 patients. The most recent results and the possible role of moabs in patients with PCNSL are summarized and discussed.

Adult↗
PubMed2002

New aspects in the treatment of AIDS-related lymphoma.

Despite of changes in the use of antiviral or chemotherapy regimens, the median survival of patients with AIDS-related lymphoma has not significantly changed until recently. However, partly due to prolonged survival with the introduction of highly active antiretroviral therapy (HAART) prognosis in AIDS patients with lymphoma seems to improve. Recently, several new treatment options have been explored in patients with lymphoma. It is hoped that novel strategies will lead to a survival benefit in these patients. In this review, we discuss the current strategies for the treatment of AIDS-related lymphoma.

Antineoplastic Agents↗