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M Gehring

Publications and source records attributed to M Gehring.

16 recordsLinked to original sources
PubMed1997

The current contribution of molecular factors to risk estimation in neuroblastoma patients.

The association of molecular characteristics with prognosis has been reported, but not their relationship with each other and their impact in the context of known clinical risk factors. In this study, data of 1249 consecutive intent-to-treat-neuroblastoma patients with more than 1 year follow-up were examined by multivariate analysis using loglinear and Cox proportional hazard regression models on a stage-related basis (stages 1-3: 600, 4S: 116, 4: 533). In a first step, risk factors were identified from 18 selected clinical variables, and risk groups defined. The second step investigated whether molecular characteristics (MYCN, LOH 1p, del 1p, CD44, N-ras, NGF-R, bcl-2, APO-1 (CD95)) contributed additional prognostic information to the model. The loglinear model demonstrated several interactions between clinical factors. By the Cox regression model, seven independent clinical risk factors were found for stages 1-3, seven for stage 4 and two for stage 4S. By subsequent introduction of all molecular variables, MYCN amplification only added significant prognostic information to the clinical factors in localised and stage 4 neuroblastoma. The models allowed the definition of risk groups for stages 1-3 patients by age (e beta = 5.09) and MYCN (e beta = 4.26), for stage 4 by MYCN (e beta = 2.78) and number of symptoms (e beta = 2.44) and for stage 4S by platelet count (e beta = 3.91) and general condition (e beta = 2.99). Molecular factors and in particular MYCN contribute significantly to risk estimation. In conjunction with clinical factors, they are powerful tools to define risk groups in neuroblastoma.

Adolescent↗
PubMed1995

The 1p deletion is not a reliable marker for the prognosis of patients with neuroblastoma.

Human neuroblastoma cells often have deletions of the distal short arm of chromosome 1 (1p). Earlier studies using chromosome analysis had suggested that the 1p deletion is correlated with a poor survival chance for the patient. We have reevaluated this possibility by analyzing 51 neuroblastomas for loss of heterozygosity (LOH) at 1p. We detected LOH in 32% of the cases. LOH did not correlate with the age of the patients at diagnosis or with tumor stage but was correlated significantly with amplification of the MYCN proto-oncogene. Nine of 10 MYCN-amplified tumors had deletions in 1p (P < 0.001). Survival chances of patients with tumors carrying MYCN amplification together with the deletion at 1p were decreased significantly (eight of nine affected patients died) compared with a patient group without any of these aberrations (P < 0.001). However, the deletion of 1p alone without MYCN amplification was not associated with a poor outcome compared with patients who had neither deletion nor amplification (only two of eight affected patients died; P = 0.803). From these data we conclude that 1p deletions are not reliable markers to determine a patient's prognosis. They may, however, identify a subgroup of neuroblastomas in which MYCN is amplified readily, resulting in rapid tumor progression.

Adult↗
PubMed1994

MYCN is retained in single copy at chromosome 2 band p23-24 during amplification in human neuroblastoma cells.

Amplification of the human N-myc protooncogene, MYCN, is frequently seen either in extrachromosomal double minutes or in homogeneously staining regions of aggressively growing neuroblastomas. MYCN maps to chromosome 2 band p23-24, but homogeneously staining regions have never been observed at this band, suggesting transposition of MYCN during amplification. We have employed fluorescence in situ hybridization to determine the status of MYCN at 2p23-24 in five human neuroblastoma cell lines. All five lines carried, in addition to amplified MYCN in homogeneously staining regions or double minutes, single-copy MYCN at the normal position. In one line there was coamplification of MYCN together with DNA of the host chromosome 12, to which MYCN had been transposed. Our results suggest a model of amplification where MYCN is retained at its original location. They further sustain the view that either the initial events of MYCN amplification or the further evolution of amplified MYCN copies follow mechanisms different from those leading to amplification of drug-resistance genes.

Chromosomes, Human, Pair 12↗
PubMed1993

Treatment of arteriovenous malformations with stereotactic radiosurgery employing both magnetic resonance angiography and standard angiography as a database.

Twenty-one arteriovenous malformations were prospectively evaluated using magnetic resonance angiography and compared with stereotactic angiography. The goals were to establish the feasibility of magnetic resonance angiography, compare it to stereotactic angiography, employ magnetic resonance angiography in follow-up, and semiquantify flow. A correlative evaluation between flow and response to stereotactic radiosurgery was carried out. Phase contrast angiograms were obtained at flow velocities of 400, 200, 100, 60, and 20 cm/sec. The fractionated velocities provided images that selectively demonstrated the arterial and venous components of the arteriovenous malformations. Qualitative assessment of the velocity within the arteriovenous malformations and the presence of fistulae were also determined by multiple velocity images. In addition, 3-dimensional time-of-flight magnetic resonance angiograms were obtained to define the exact size and shape of the nidus. This technique also permitted evaluation of the nidus and feeding arteries for the presence of low flow aneurysms. Correlation between the two imaging modalities was carried out by subjective and semiquantitative estimation of flow velocity and estimation of nidus size. The following velocity parameters were employed: fast, intermediate, slow, and none (arteriovenous malformation obliterated). In 19 of 21 (90.5%) arteriovenous malformations, magnetic resonance angiography was equal or superior to stereotactic angiography for flow quantification and visualization of the nidus. Only 2 of 21 arteriovenous malformations were better demonstrated by stereotactic angiography than by magnetic resonance angiography (failure rate of 9.5%). The nidus size in one case was clearly underestimated by stereotactic angiography and would have resulted in a geographic miss without magnetic resonance angiography. Seven post-radiosurgery arteriovenous malformations were evaluated for follow-up with both magnetic resonance angiography and stereotactic angiography. In 6 of 7 arteriovenous malformations, magnetic resonance angiography response matched stereotactic angiography response. Correlation of flow with outcome was carried out for 14 arteriovenous malformations using magnetic resonance angiography only. Interestingly, all nine arteriovenous malformations with intermediate or slow flow demonstrated partial or complete obliteration; whereas only 3 of 5 fast flow arteriovenous malformations achieved a response with a median follow-up of 10 months. This early analysis suggests that slower flowing arteriovenous malformations may obliterate faster after stereotactic radiosurgery and flow parameters could be employed to predict response. In conclusion, magnetic resonance angiography permits semiquantitative flow velocity assessment and may therefore be superior to stereotactic angiography. An additional advantage of magnetic resonance angiography is the generation of serial transverse images which can replace the conventional CT scan employed for stereotactic radiosurgery treatment planning.(ABSTRACT TRUNCATED AT 400 WORDS)

Cerebral Angiography↗
PubMed1993

Mutations of the p53 tumor suppressor gene in neoplasms of the human nervous system.

A variety of neoplasms of the human nervous system were analyzed for the presence of mutations in the p53 tumor suppressor gene. DNA was extracted from frozen or formalin-fixed, paraffin-embedded material. Single-strand conformation polymorphism (SSCP) analysis for exons 5-8 was followed by direct DNA sequencing. Mutations leading to an amino acid change were found in three of 11 (27%) low-grade (World Health Organization (WHO) Grade II) astrocytomas. They were located in codon 183 (TCA-->TGA) of exon 5, codon 237 (ATG-->ATA) of exon 7, and codon 273 (CGT-->CAT) of exon 8. In one of these cases, the sequence indicated loss of the wild-type allele. Of 12 juvenile pilocytic astrocytomas (WHO Grade I), none contained a p53 mutation, suggesting a different molecular basis for this childhood neoplasm. Except for a mutation in one of seven (14%) meningeal hemangiopericytomas (codon 238; TGT-->TTT, Cys-->Phe), no mutations were observed in exons 5-8 of the p53 gene in any of the following tumors of the nervous system and its coverings: 13 schwannomas, 12 central neurocytomas, 22 meningiomas, 10 choroid plexus papillomas and carcinomas, and 30 neuroblastomas of the sympathetic nervous system. These and published data support the view that p53 mutations are frequently involved both in low-grade and progressive (anaplastic) astrocytomas, including glioblastomas multiforme. Oligodendrogliomas, medulloblastomas, meningiomas, and hemangiopericytomas rarely (< 15%) show p53 mutations in exons 5-8, whereas none of the remaining nervous system neoplasms revealed evidence of an involvement of the p53 gene in their development.

Adolescent↗
PubMed1993

Magnetic resonance angiography: a three-dimensional database for assessing arteriovenous malformations. Technical note.

Stereotactic angiography has long been the "gold standard" in the diagnosis of patients with arteriovenous malformations (AVM's). Although orthogonal or stereoshift images may suffice in discerning the shape and location of spherical malformations, an exact analysis and assessment of most nonspherical malformations are hampered by the fact that stereotactic angiographic images compress three-dimensional (3-D) data into two-dimensional views. As a consequence, the complex 3-D shape of an AVM can never be fully and truly discerned from conventional angiography. With the recent explosion of radiosurgical techniques, more and more AVM's are being treated noninvasively. These radiosurgical techniques require 3-D visualization to maximize nidus coverage and minimize normal brain irradiation. Alternatives to stereotactic angiography are therefore desperately needed. An entire new family of pulse sequences is now available that permits visualization of the vascular system using magnetic resonance imaging. A brief technical review of magnetic resonance angiography is presented, and its potential role(s) in the assessment and radiosurgical treatment of AVM's is explored.

Humans↗
PubMed1992

Deletion mapping of chromosomes 14q and 1p in human neuroblastoma.

It has been suggested that loss of heterozygosity (LOH) on the short arm of chromosome 1 is a critical event for the development of neuroblastoma, and we have previously shown frequent LOH on chromosome 14 in neuroblastoma. To pursue these observations, especially to define further the regions which are commonly deleted in the tumor, we examined for allelic losses in 27 cases of neuroblastomas by using a number of polymorphic DNA markers for chromosomes 14q and 1p. LOH was observed in 10 out of the 25 informative cases (40%) on chromosome 14q and in eight out of the 21 informative cases (38%) on 1p. The commonly deleted regions were distal to the D14S13 locus (14q32-qter) on chromosome 14 and distal to the D1S112 locus (1p36.1-pter) on chromosome 1. These results strongly suggest that tumor-suppressor genes important in the pathogenesis of human neuroblastoma are located on the distal part of both chromosomes 14q and 1p.

Alleles↗
PubMed1988

The children of alcoholics life-events schedule: a stress scale for children of alcohol-abusing parents.

Children of alcoholic parents have been shown to be at risk for the development of mental health problems. However, there is little empirical research that would allow one to determine which of these children are most at risk. Hypothesizing that the amount of parental drinking-related stress a child experiences may be a factor that discriminates those children of alcoholics who are most at risk from others, the Children of Alcoholics Life-Events Schedule (COALES) was developed. Using samples of high-school students, the COALES was found to have satisfactory test-retest reliability, internal-consistency reliability and construct and concurrent validity. Children who self-identified as having an alcoholic parent reported higher levels of negative events and lower levels of positive events than did their peers from nonalcoholic homes. Scores on the positive- and negative-event subscales were significantly correlated with the children's scores on measures of anxiety and depression.

Adolescent↗
PubMedDate not supplied

Investigation of the convolution method for polyenergetic spectra.

The distribution of absolute dose per unit fluence from polyenergetic photon beams impinging upon a water phantom was calculated using two convolution approaches that properly account for beam hardening effects. Dose deposition kernels calculated previously using the EGS4 Monte Carlo code are convolved with the primary terma to give the dose for monoenergetic photon beams of energies ranging from 100 kev to 50 MeV. A polyenergetic dose distribution is composed of separately calculated monoenergetic components, which are appropriately weighted with the fluence spectrum to yield the polyenergetic dose distribution. Alternatively, a single convolution for the polyenergetic beam is considered, where a composite polyenergetic kernel is convolved with the respective polyenergetic terma. The effects of the polyenergetic kernel variance due to beam hardening as well as the effect of tilting the kernels for a diverging beam geometry were also examined. The depth dose data produced using the two proposed methods were compared with measured data and Monte Carlo simulations and showed good agreement.

Biophysical Phenomena↗
PubMedDate not supplied

Bellyboard device reduces small bowel displacement.

The ability to cure several pelvic malignancies is hampered by the inability to deliver doses greater than 45 to 50 Gy, beyond which radiation enteritis becomes dose-limiting. The design and fabrication of a device that allows exclusion of small bowel from the pelvis during radiation therapy are described in this study. A prospective dose-volume analysis conducted on 30 patients reveals a 66 percent reduction in the volume of small bowel within the radiation portals.

Equipment Design↗