Biomedical subjects

Petra Schmalbrock

Publications and source records attributed to Petra Schmalbrock.

5 recordsLinked to original sources

PubMed2003

Experimental treatment of Epstein-Barr virus-associated primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) that arises in immune-deficient patients is an aggressive B-cell neoplasm that is universally associated with the EBV. Patients with EBV(+) PCNSL face a particularly poor prognosis with median survival times of 2-12 months despite aggressive management with radiation therapy. We have developed a preclinical model of EBV(+) PCNSL to explore strategies that specifically target EBV-infected B lymphoblasts in vivo. Stereotactic implantation of EBV-transformed human lymphoblastoid B-cell lines into the caudate nucleus of the nude rat resulted in lethal CNS tumor burden manifested by the onset of focal neurological symptoms within 21 days. Histological evaluation at autopsy revealed a multifocal, perivascular human EBV(+) lymphoblastic B-cell infiltrate that displayed a latency type III EBV gene expression profile similar to PCNSL that develops in some immune-deficient patients. Radiation (1600 cGy) of lymphoblastoid B-cell lines resulted in up-regulation of the EBV thymidine kinase (EBV-TK) transcript and sensitization of these cells to drug-induced apoptosis using nucleoside analogs. Enhanced expression of EBV-TK mRNA in EBV(+) PCNSL tumors by radiation therapy occurred in a dose-dependent fashion. In vivo trials using the nude rat PCNSL model demonstrated significantly improved mean survival time (MST) with single fraction whole-brain radiotherapy (WBRT) and antiviral therapy consisting of zidovudine (AZT) and ganciclovir (GCV; MST 41.3 +/- 3.3 days; P = 0.05), compared with either antiviral therapy (MST 32.1 +/- 1.1 days) or WBRT alone (MST 22 +/- 0.8 days). We found constitutive and abundant EBV-TK mRNA expression in a stereotactic core biopsy specimen from a solid organ transplant patient with EBV(+) PCNSL. Withdrawal of immunosuppression did not result in disease regression. This patient achieved a complete response after therapy with high-dose AZT and GCV in the absence of WBRT, and remains in remission on oral maintenance AZT/GCV therapy 3 years after diagnosis. These results suggest that antiviral therapies can be effectively explored in vivo using a preclinical animal model of human EBV(+) PCNSL with subsequent translation to patients with EBV(+) PCNSL.

Animals↗

PubMed2002

Three-dimensional numerical simulations of susceptibility-induced magnetic field inhomogeneities in the human head.

Three-dimensional numerical simulations of the static magnetic field in the human head were carried out to assess the field inhomogeneity due to magnetic susceptibility differences at tissue interfaces. We used a finite difference method and magnetic permeability distributions obtained by segmentation of computed tomography images. Computations were carried out for four models, consisting of the head and the neck; the head, neck, and shoulders; the head, neck, and thorax; and the head tilted backwards, including the neck and the shoulders. Considerable magnetic field inhomogeneities were observed in the inferior frontal lobes and inferior temporal lobes, particularly near the sphenoid sinus and the temporal bones. Air/tissue interfaces at the shoulders were found to induce substantial magnetic field inhomogeneities in the occipital lobes and the cerebellum, whereas air/tissue interfaces in the lungs appeared to have less influence on the magnetic field in the brain. Tilting the head backwards could significantly reduce the field inhomogeneities superior to the planum sphenoidale as well as in the occipital lobes and the cerebellum.

Artifacts↗

PubMed2002

Virtual temporal bone dissection: an interactive surgical simulator.

OBJECTIVE: Our goal was to integrate current and emerging technology in virtual systems to provide a temporal bone dissection simulator that allows the user interactivity and realism similar to the cadaver laboratory. STUDY DESIGN: Iterative design and validation of a virtual environment for simulating temporal bone dissection. SETTING: University otolaryngology training program with interdisciplinary interaction in a high-performance computer facility. RESULTS: The system provides visual, force feedback (haptic), and aural interfaces. Unlike previous "fly through" virtual systems, this environment provides a richer emulation of surgical experience. CONCLUSION: The system provides a high level of functional utility and, through initial evaluations, demonstrates promise in adding to traditional training methods. SIGNIFICANCE: The system provides an environment to learn temporal bone surgery in a way similar to the experience with cadaver material where the subject is able to interact with the data without constraints (nondeterministic). Eventually, it may provide the "front end" to a large repository of various temporal bone pathologies that can be accessed through the Internet.

Algorithms↗

PubMed2002

Functional magnetic resonance imaging as a tool for investigating amblyopia in the human visual cortex: a pilot study.

PURPOSE: This study investigates interocular differences in the level and extent of cortical activation in amblyopic and normal subjects. SUBJECTS AND METHODS: Blood oxygenation level dependent functional magnetic resonance imaging (FMRI) was performed at 1.5 T. A total of 5 subjects with amblyopia and 6 control subjectswere recruited. Visual stimuli included a homogeneous field flickering at 8 Hz and vertical sinusoidal gratings with spatial frequencies of 0.5, 1, and 2 cycles per degree of visual angle (counterphased at 8 Hz). Baseline images were taken in darkness. Stimuli were presented monocularly and binocularly. Data analysis was constrained to the occipital cortex, including striate and extrastriate areas. An absolute percent difference measure defined interocular differences in terms of total area, average level of activation, and a pooled activation parameter. RESULTS: Subjects with amblyopia exhibited a significantly larger (P <.05) interocular activation difference compared to controls. The level of activation driven by monocular stimulation of the amblyopic eye was reduced by 8.25% +/- 1.3% relative to the dominant eye. Controls showed an interocular difference in level of activation of 4.82% +/- 0.74%. The total area of activation driven by the amblyopic eye was reduced by 34.86% +/- 6.25% relative to the dominant eye. Controls showed an interocular difference in total area of activation of 20.80% +/- 3.67%. Subjects with amblyopia also manifested significantly greater (P <.05) cortical area and level of activation differences between the binocular and monocular states; the dominant eye response differed less from the binocular response than did the amblyopic eye response. CONCLUSION: FMRI is sensitive to amblyopia-related deficits in the human occipital cortex and, therefore, has potential as a tool for basic amblyopia research.

Adolescent↗

PubMed2002

Visualization of microvascularity in glioblastoma multiforme with 8-T high-spatial-resolution MR imaging.

We used 8-T high-spatial-resolution gradient-echo MR imaging to directly visualize microvascularity in pathologically proved glioblastoma multiforme. Images were compared with 1.5-T high-spatial-resolution fast spin-echo T2-weighted images and digital subtraction angiograms. Preliminary data indicate that 8-T high-spatial-resolution MR imaging may enable the identification of areas of abnormal microvascularity in glioblastoma multiforme that are not visible with other routine clinical techniques.

Adult↗