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Michael Scholz

Publications and source records attributed to Michael Scholz.

At least 19 recordsLinked to original sources
PubMed2006

Radiation tolerance of the rat spinal cord after 6 and 18 fractions of photons and carbon ions: experimental results and clinical implications.

PURPOSE: The tolerance of the rat spinal cord to photon and carbon ion irradiations was investigated to determine the relative biologic effectiveness (RBE) of carbon ions ((12)C) in the plateau region and in a 1 cm spread-out Bragg-peak. METHODS AND MATERIALS: The cranial part of the cervical and thoracic spinal cord of 336 rats was irradiated with 6 or 18 fractions (Fx) of photons or (12)C-ions, respectively. Animals were followed up for 300 days for the onset of paresis grade II and dose-response curves were calculated. RESULTS: The D(50)-values (dose at 50% complication probability) were 42.9 +/- 0.5 Gy, 62.2 +/- 0.9 Gy (6 and 18 Fx, (12)C-plateau) and 19.2 +/- 0.2 Gy, 17.6 +/- 0.2 Gy (6 and 18 Fx (12)C-peak), respectively. For photons, the D(50)-values were 57.0 +/- 0.7 Gy for 6 and 88.6 +/- 0.7 Gy for 18 Fx. The corresponding RBE-values were 1.33 +/- 0.02, 1.42 +/- 0.02 (6 and 18 Fx, (12)C-plateau) and 2.97 +/- 0.05, 5.04 +/- 0.08 (6 and 18 Fx (12)C-peak), respectively. Including data of a previously performed experiment for 1 and 2 Fx (1) the parameter alpha/beta of the LQ-model was found to be 2.8 +/- 0.4 Gy, 2.1 +/- 0.4 Gy and 37.0 +/- 5.3 Gy for photon-, (12)C-plateau- and (12)C-peak irradiations, respectively. CONCLUSIONS: Carbon ion irradiations of the spinal cord are significantly more effective in the peak than in the plateau region. The alpha/beta-values indicate a significant fractionation effect only for the plateau irradiations. In the Bragg-peak, the applied RBE-model correctly describes the main features although it generally underestimates the RBE by 25%. In the plateau region, maximum deviations of up to 20% were found. The acquired data contribute significantly to the validation of the applied RBE-model.

Algorithms↗
PubMed2006

Choroidal innervation and optic neuropathy in macacque monkeys with laser- or anterior chamber perfusion-induced short-term elevation of intraocular pressure.

Long-term intraocular pressure (IOP) elevation leads to a significant reduction of the intrinsic choroidal innervation and axon loss in the optic nerve. In this study we investigated early changes in these tissues in order to clarify the putative sequence of events between choroidal ganglion cell loss and optic nerve axon loss in 19 monkeys with experimentally induced glaucoma. After 1 month of increased IOP, severe optic neuropathy but no reduction of choroidal ganglion cells (CGC) was detectable. Beginning at 2 months after treatment signs of degeneration in CGC morphology were observed. Laser treatment of the trabecular meshwork without IOP elevation caused no changes in choroidal innervation. Our results show that there is no apparent association between reduction of CGC and optic neuropathy in the early stages of IOP elevation.

Animals↗
PubMed2006

Is there an indication for frozen section examination of the ureteral margins during cystectomy for transitional cell carcinoma of the bladder?

PURPOSE: We evaluated the incidence of pathological findings of the ureter at cystectomy for transitional cell carcinoma of the bladder and assessed the usefulness of intraoperative frozen section examination of the ureter. MATERIALS AND METHODS: Histopathological findings of ureteral frozen section examination were compared to the corresponding permanent sections and the diagnostic accuracy of frozen section examination was evaluated. These segments were then compared to the more proximal ureteral segments resected at the level where they cross over the common iliac arteries. The histopathological findings of the ureteral segments were then correlated for upper urinary tract recurrence and overall survival. RESULTS: Transitional cell carcinoma or carcinoma in situ was found on frozen section examination of the distal ureter in 39 of 805 patients (4.8%) and on permanent sections in 29 (3.6%). In 755 patients the false-negative rate of frozen section examination of the ureters was 0.8%. Of the patients with carcinoma in situ diagnosed on the first frozen section examination 80% also had carcinoma in situ in the bladder. Transitional cell carcinoma or carcinoma in situ in the most proximally resected ureteral segments was found in 1.2% of patients. After radical cystectomy there was tumor recurrence in the upper urinary tract in 3% of patients with negative ureteral frozen section examination and in 17% with carcinoma in situ on frozen section examination. CONCLUSIONS: Routine frozen section examination of the ureters at radical cystectomy is only recommended for patients with carcinoma in situ of the bladder, provided the ureters are resected where they cross the common iliac arteries.

Carcinoma in Situ↗
PubMed2005

Early, partly anticipatory, neural oscillations during identification set the stage for priming.

Perceptual priming is a fundamental long-term memory capability by which exposure to a stimulus improves later perceptual processing of that stimulus. A widespread hypothesis is that priming is the later result of perceptual learning during stimulus identification. Testing this hypothesis involves isolating priming without explicit memory, and appropriately measuring brain activity during initial experimental exposure to assess whether brain activity related to identification differs as a function of later priming. Here, we show, using magnetoencephalography (MEG), that words primed in a later test are distinguished from unprimed words at initial exposure by (a) more specific responses in perceptual brain areas, indicated by an early (within 240 ms after word onset) decrease in amplitude but increase in phase alignment of beta and gamma oscillations, and (b) improved coordination of responses across perceptual and higher brain areas in the same time window, indicated by an increase in interareal phase synchrony of alpha oscillations. The increase in interareal phase synchrony partly started already in the pre-stimulus period, approximately 60-80 ms prior to word onset, showing that the improved coordination of responses across areas was partly anticipatory. The anatomy and early timing of these patterns reveal a neural link between identification and long-term memory. The pre-stimulus findings additionally show that priming is related to the stimulus-specific anticipatory state of visual identification areas at initial exposure.

Adult↗
PubMed2005

Ectopic norrin induces growth of ocular capillaries and restores normal retinal angiogenesis in Norrie disease mutant mice.

Norrie disease is an X-linked retinal dysplasia that presents with congenital blindness, sensorineural deafness, and mental retardation. Norrin, the protein product of the Norrie disease gene (NDP), is a secreted protein of unknown biochemical function. Norrie disease (Ndp(y/-)) mutant mice that are deficient in norrin develop blindness, show a distinct failure in retinal angiogenesis, and completely lack the deep capillary layers of the retina. We show here that the transgenic expression of ectopic norrin under control of a lens-specific promoter restores the formation of a normal retinal vascular network in Ndp(y/-) mutant mice. The improvement in structure correlates with restoration of neuronal function in the retina. In addition, lenses of transgenic mice with ectopic expression of norrin show significantly more capillaries in the hyaloid vasculature that surrounds the lens during development. In vitro, lenses of transgenic mice in coculture with microvascular endothelial cells induce proliferation of the cells. Transgenic mice with ectopic expression of norrin show more bromodeoxyuridine-labeled retinal progenitor cells at embryonic day 14.5 and thicker retinas at postnatal life than wild-type littermates, indicating a putative direct neurotrophic effect of norrin. These data provide direct evidence that norrin induces growth of ocular capillaries and that pharmacologic modulation of norrin might be used for treatment of the vascular abnormalities associated with Norrie disease or other vascular disorders of the retina.

Animals↗
PubMed2005

Pathophysiologic changes in the optic nerves of eyes with primary open angle and pseudoexfoliation glaucoma.

PURPOSE: To determine whether differences in the optic nerve occur in eyes with primary versus secondary open-angle glaucoma. METHODS: Optic nerves obtained at autopsy from 36 eyes with primary open-angle glaucoma (POAG) and 15 with pseudoexfoliation glaucoma (PEXG) were studied quantitatively and qualitatively. Axon counts, fibrosis, capillary number and density, and arteriosclerotic changes were assessed in the postlaminar optic nerve and compared to normal age-matched autopsy eyes. Changes in composition of extracellular matrix components were evaluated by immunohistochemistry and electron microscopy. RESULTS: Marked differences were found between POAG and PEXG. Axon loss in eyes with POAG but not in PEXG was associated with increasing connective tissue in the septa and surrounding the central retinal vessels, including increased amounts of type IV and VI collagen. The total number of capillaries decreased with the loss of axons in both POAG and PEXG. POAG nerves, however, had a decrease in the density of capillaries, whereas in PEXG the capillary density did not change with axon loss. Arteriosclerotic changes were more common in glaucomatous eyes than in age-matched control eyes. CONCLUSIONS: The difference in morphology of the optic nerves between POAG and PEXG indicates that in eyes with POAG, elevated IOP cannot be the only pathogenetic factor in glaucomatous optic neuropathy. Additional factors, inducing fibrosis and loss of capillaries, seem to be involved. Such additional factors may also contribute to the clinical finding in POAG that nerves can become damaged without elevation of intraocular pressure.

Aged↗
PubMed2004

A method for the automatic segmentation of autoradiographic image stacks and spatial normalization of functional cortical activity patterns.

This paper introduces two new methods for the automatic anatomical and functional analysis of neurobiological autoradiographic image stacks, such as 2-fluoro-deoxyglucose (2FDG) images. The difficulty in the evaluation of these "2(1/2)D" datasets is that they do not inherently represent a continuous 3D data volume (as generated by MRI or CT), but consist of a stack of images from single tissue slices, suffering from unavoidable preparation artifacts. In the first part of the paper, a semi-automatic segmentation method is presented which generates a 3D surface model of certain brain structures and which is robust against different cutting directions with respect to the brain coordinate system. The method saves man-hours compared to manual segmentation and the results are highly reproducible. In the second part, a fully automatic method for the extraction, analysis and 3D visualization of functional information is described, which allows not only a more accurate localization of activation sites, but also greatly enhances the comparability of different individuals. Results are shown for 2FDG autoradiographs from rat brains under acoustical stimulation.

Animals↗
PubMed2004

New methods for the computer-assisted 3-D reconstruction of neurons from confocal image stacks.

Exact geometrical reconstructions of neuronal architecture are indispensable for the investigation of neuronal function. Neuronal shape is important for the wiring of networks, and dendritic architecture strongly affects neuronal integration and firing properties as demonstrated by modeling approaches. Confocal microscopy allows to scan neurons with submicron resolution. However, it is still a tedious task to reconstruct complex dendritic trees with fine structures just above voxel resolution. We present a framework assisting the reconstruction. User time investment is strongly reduced by automatic methods, which fit a skeleton and a surface to the data, while the user can interact and thus keeps full control to ensure a high quality reconstruction. The reconstruction process composes a successive gain of metric parameters. First, a structural description of the neuron is built, including the topology and the exact dendritic lengths and diameters. We use generalized cylinders with circular cross sections. The user provides a rough initialization by marking the branching points. The axes and radii are fitted to the data by minimizing an energy functional, which is regularized by a smoothness constraint. The investigation of proximity to other structures throughout dendritic trees requires a precise surface reconstruction. In order to achieve accuracy of 0.1 microm and below, we additionally implemented a segmentation algorithm based on geodesic active contours that allow for arbitrary cross sections and uses locally adapted thresholds. In summary, this new reconstruction tool saves time and increases quality as compared to other methods, which have previously been applied to real neurons.

Algorithms↗
PubMed2004

Chromosome fragmentation after irradiation with C ions.

The premature chromosome condensation (PCC) technique has been used to compare chromatin breakage and repair in non-cycling CHO-K1 cells following high LET (C ions) and low LET (X-rays) irradiation. For both radiation qualities the average initial number of excess PCC fragments increases linearly with dose. However, the frequency of chromatin breaks follows the pattern of energy deposition and at higher LET values reveals clustering due to the large number of ionizing events being concentrated in a small volume of the cell nucleus. In consequence, the distribution of PCC chromosomes plus excess fragments among cells has followed Poisson statistics after X-ray irradiation while the overdispersion of the frequencies has been observed after C-irradiation indicating that a single particle traversal through a cell nucleus can produce multiple chromatin lesions.

Animals↗
PubMed2003

Feasibility and toxicity of combined photon and carbon ion radiotherapy for locally advanced adenoid cystic carcinomas.

PURPOSE: To investigate clinical feasibility and toxicity of combined photon and carbon ion radiotherapy in locally advanced adenoid cystic carcinomas (ACC) within a prospective Phase I/II trial. METHODS AND MATERIALS: Between September 1998 and April 2002, 16 patients with histopathologically proven ACC and residual macroscopic tumor were treated with combined photon RT and a carbon ion boost to the macroscopic tumor. Median total tumor dose within the gross tumor volume (GTV) was 72 GyE. Photon radiation therapy (RT) consisted of fractionated stereotactic RT in 7 patients; 9 patients received stereotactic intensity-modulated RT. Carbon ion boost was delivered by intensity-controlled raster scanning at the heavy ion synchrotron (SIS) at the Heavy Ion Research Center (GSI) in Darmstadt. RESULTS: Median follow-up was 12 months. Three patients developed locoregional recurrences 9, 11, and 24 months after RT, respectively. Actuarial local control rates were 80.8% and 64.6% at 1 and 3 years, respectively. Overall survival rates were 100% and 83.3% at 1 and 3 years, respectively. Acute side effects greater than Common Toxicity Criteria (CTC) Grade 2 were observed in 2 patients; no patient developed late effects > CTC Grade 2. CONCLUSIONS: Combined photon and carbon ion RT is feasible and effective in patients with locally advanced ACC. Acute and late toxicity is moderate with respect to the delivered tumor doses and in accordance with the radiobiologic modeling. A Phase III trial is designed.

Adult↗
PubMed2003

Carbon ion radiotherapy for chordomas and low-grade chondrosarcomas of the skull base. Results in 67 patients.

PURPOSE: To prospectively evaluate outcome and toxicity after carbon ion radiotherapy (RT) in chordomas and low-grade chondrosarcomas. PATIENTS AND METHODS: Between September 1998 and December 2001, 74 patients were treated for chordomas and chondrosarcomas with carbon ion RT at the "Gesellschaft für Schwerionenforschung" (GSI). Seven patients reirradiated with reduced carbon ion doses after conventional RT were excluded from the analysis, leaving 67 evaluable patients (44 chordomas and 23 chondrosarcomas) who received a full course of carbon ion therapy. Tumor-conform application of carbon ion beams was realized by intensity-controlled raster scanning with active energy variation. Three-dimensional treatment planning included intensity modulation and biological plan optimization. A median dose of 60 GyE was applied to the target volume within 20 consecutive days at a dose of 3.0 GyE per fraction. RESULTS: Median follow-up was 15 months (range 3-46 months). At 3 years, actuarial local control was 100% for chondrosarcomas and 87% for chordomas, respectively. Partial tumor remission was observed in 14/44 (31%) chordoma patients and in 4/23 (17%) chondrosarcoma patients. At 3 years, actuarial overall survival was 100% for chondrosarcomas and 89% for chordomas, respectively. No severe side effects > CTC degrees III have been observed. CONCLUSIONS: These data demonstrate the clinical efficiency and safety of scanning beam delivery of carbon ion beams in patients with skull base chordomas and chondrosarcomas. The observation of tumor regressions at a dose level of 60 GyE may indicate that the biological effectiveness of carbon ions in chordomas and chondrosarcomas is higher than initially estimated.

Adolescent↗
PubMed2003

A new point-based warping method for enhanced and simplified analysis of functional brain image data.

Comparison of brain imaging data requires the exact matching of data sets from different individuals. Warping methods, used to optimize matching of data sets, can exploit either local gray value distribution or identifiable reference points within the images to be compared. Gray value-based warping, which is more comfortable, cannot be used if gray values include functional information that should be compared between images. A major drawback in the use of point-based warping methods is the lack of methods for efficient and precise definition of reference points (landmarks) within comparable data sets. Here, we present a novel approach to automatically detect sufficient numbers of landmarks, which is based on 3D differential operators. In addition, we have developed a new distance-weighted warping method, which optimizes individual local weighting factors of displacement vectors. The quality of the methods was evaluated using a set of autoradiographs documenting the metabolic activity of gerbil brains after acoustic stimulation. The new warping method was compared with known methods of landmark-based warping, i.e., warping with radial basis functions and with distance-weighted methods. For the data sets presented in this study our new optimized warping method produced an increase in linear cross correlation of 4.44%, an increase in volume overlap index of 1.55%, and a decrease in the registration error of 36.2%. In addition, the detection of functional differences was improved after warping. Therefore, the new method is a powerful tool, which enhances the comparison of complex biological structures and the quantitative evaluation of functional imaging data.

Algorithms↗
PubMed2003

Stage I testicular cancer.

PURPOSE OF REVIEW: To review current developments in the management of patients with testicular cancer, with special emphasis on risk factors for the primary tumour and treatment options for clinical stage I testicular germ cell tumours. RECENT FINDINGS: The management of patients with testicular cancer has substantially improved over the past 25 years. Current concepts for treating localized and regional disease have been influenced by effective systematic chemotherapy. At present, cure rates approach nearly 100% for low-stage disease and more than 80% for advanced disease. SUMMARY: Retroperitoneal lymph node dissection is still favoured as the therapy of choice for clinical stage I non-seminomatous germ cell tumours in many centres, but as risk factors for the primary tumour have become better understood, surveillance and risk-adapted therapy, including surveillance for low-risk patients and adjuvant chemotherapy for the high-risk group, is now being considered a therapeutic option particularly in European centres. Adjuvant radiotherapy is still the gold standard for the treatment of patients with clinical stage I seminoma, but the relapse rate of 19% and a 5-year overall survival of 97.7% make surveillance a possible therapeutic option. The results of phase II and III trials should soon provide additional information on carboplatin for single-agent adjuvant chemotherapy.

Chemotherapy, Adjuvant↗
PubMed2003

Radiation tolerance of the rat spinal cord after single and split doses of photons and carbon ions.

The sensitivity of the rat spinal cord to single and split doses of radiation and the resulting relative biological effectiveness (RBE) were determined for carbon-ion irradiations (12C) in the plateau and Bragg-peak regions. The cranial part of the cervical and thoracic spinal cords of 180 rats were irradiated with one or two fractions of 12C ions or photons, respectively. Dose-response curves for the end point symptomatic myelopathy were established, and the resulting values for the ED50 (dose for 50% complication probability) were used to determine the RBEs. A median latency for myelopathy of 167 days (range, 121-288 days) was found. The ED50 values were 17.1 +/- 0.8 Gy, 24.9 +/- 0.7 Gy (one and two fractions, 12C plateau) and 13.9 +/- 0.8, 15.8 +/- 0.7 Gy (one and two fractions, 12C Bragg peak), respectively. For photons we obtained ED50 values of 24.5 +/- 0.8 Gy for single doses and 34.2 +/- 0.7 Gy when two fractions were applied. The corresponding RBEs were 1.43 +/- 0.08, 1.37 +/- 0.12 (one and two fractions, 12C plateau) and 1.76 +/- 0.05, 2.16 +/- 0.11 (one and two fractions, 12C Bragg peak), respectively. Hematoxylin and eosin staining revealed necrosis of the white matter in the spinal cord in all symptomatic animals. In summary, from one- and two-fraction photon, 12C plateau and Bragg-peak irradiation of the rat spinal cord, we have established RBEs as well as the individual ED50's. From the latter there is a clear indication of repair processes for fractionated photons and 12C plateau ions which are significantly reduced by using Bragg-peak ions. Additional studies are being carried with 6 and 18 fractions to further refine and define the RBE and ED50 values and estimate the alpha/beta ratios.

Adaptation, Physiological↗
PubMed2002

Impact of thrombophilic gene mutations on thrombosis risk in patients with gastrointestinal carcinoma.

BACKGROUND: Patients with malignancies have an increased risk for thromboembolic events due to the release of tissue factor by the tumor, damage to the vessel wall, and immobilization. Moreover, tumors may improve their growth and metastatic spread by utilizing the coagulation system. To date, no information is available on the additional role of prothrombotic mutations in these patients. METHODS: The prevalence of the factor V Leiden mutation (FVL) and the prothrombin G20210A mutation and of homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T substitution has been analyzed in a cohort of 175 patients with gastrointestinal adenocarcinoma by the polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: 6.9% of the patients were heterozygous for FVL, 5.7% were heterozygous for the prothrombin mutation, and 9.7% were homozygous for the MTHFR C677T mutation was detected in 9.7% of patients. Compared with the normal population, we found an increased prevalence of the prothrombin G20210A substitution (5.7% vs. 0.8%, P = 0.028). Thromboses were absent in 147 patients (Group A), whereas 28 of the patients suffered from thromboses during the period following tumor diagnosis (Group B). In Group A, 6.8% of the patients and 21.4% of the patients in Group B had a thrombosis before the diagnosis of cancer (P = 0.025, odds ratio [OR] 3.7). Heterozygous FVL was present in 4.8% of the patients in Group A and in 17.9% of the patients in Group B (P = 0.026, OR 4.4). In patients with thromboses before the detection of the tumor, the risk was elevated 6.3-fold (25.0% vs 5.0%, P = 0.015). Heterozygosity for the prothrombin mutation and homozygosity for the MTHFR C677T substitution did not increase the incidence of thromboses. CONCLUSIONS: We demonstrated a significant effect of FVL on thrombosis in patients with malignant disease. Most thromboses occurred during the first months after tumor diagnosis, implicating diagnostic and therapeutic procedures as important nongenetic risk factors for venous thromboembolism. Our data also indicate that the prothrombin G20210A mutation may be a possible cofactor in cancer pathogenesis.

Adenocarcinoma↗
PubMed2002

Acute radiation-induced toxicity of heavy ion radiotherapy delivered with intensity modulated pencil beam scanning in patients with base of skull tumors.

PURPOSE: The purpose of this paper is to evaluate acute radiation-induced toxicity of carbon ion therapy. MATERIAL AND METHODS: From December 1997 to November 2000, 37 patients with chordomas and low-grade chondrosarcomas of the skull base have been treated with carbon ions at the heavy ion synchrotron (SIS) at GSI, Darmstadt. Tumor-conformal application of carbon beams was realized by intensity-controlled raster scanning in combination with pulse-to-pulse energy variation. The treatment planning procedure included a biological plan optimization. We applied a cobalt-Gray equivalent dose of 60GyE. Acute toxicity was assessed according to the common toxicity criteria (CTC). RESULTS: Acute toxicity included skin reactions ( degrees I+ degrees II) in four patients, mucositis ( degrees I- degrees III) in eight patients, otitis and middle ear effusion in four, sinusitis in four, nausea/weight loss in one and edema of the temporal lobes in one patient. In two patients, preexisting neurological symptoms worsened. We did not observe acute morbidity > degrees III of normal tissues. CONCLUSION: Scanning beam delivery of heavy charged particles is safe and reliable. No unexpected acute dose limiting toxicity was observed. With regard to toxicity, a substantial improvement compared to passive beam shaping technology is achieved.

Adolescent↗
PubMed2002

Should systematic reviews include non-randomized and uncontrolled studies? The case of acupuncture for chronic headache.

We aimed to investigate: (1) whether patient and intervention characteristics, design-independent quality aspects, and response rates differ between randomized and non-randomized trials of acupuncture for chronic headache; (2) whether non-randomized studies provide useful additional information (regarding long-term effects, prognostic factors, adverse effects, and generalizability); (3) reasons for potential differences in response rates. Studies including at least five patients and reporting clinical outcome data were identified through searches in Medline, Embase, the Cochrane Controlled Trials Register, other databases and checking of bibliographies. Twenty-four randomized trials and 35 non-randomized studies (five non-randomized controlled cohort studies, 10 prospective uncontrolled studies, 10 case series, and 10 cross-sectional surveys) met the inclusion criteria. Studies were heterogeneous regarding patients, interventions, outcome measurements and results. On average, randomized trials had smaller sample sizes, met more quality criteria, and had lower response rates (0.59 [95% confidence interval 0.48-0.69] vs. 0.78 [0.72-0.83]). Whether randomized or not, studies meeting more quality criteria had lower response rates. Non-randomized studies did not have significantly longer follow-up periods, three included an analysis of prognostic variables, only one reported on adverse effects, and the degree of generalizability was unclear. In the case of acupuncture for chronic headache, non-randomized studies confirmed the finding of a systematic review of randomized trials that the treatment is likely to be effective but provided little relevant additional information on long-term effects, prognostic factors, and adverse effects.

Acupuncture↗