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Biomedical subjects

P Burger

Publications and source records attributed to P Burger.

At least 19 recordsLinked to original sources
PubMed2007

Pre-radiation chemotherapy with response-based radiation therapy in children with central nervous system germ cell tumors: a report from the Children's Oncology Group.

BACKGROUND: This Phase II study was designed to determine response to chemotherapy and survival after response-based radiation (RT) in children with CNS germ cell tumors. PROCEDURE: Children with germinomas and normal markers received cisplatin 100 mg/m(2) + etoposide, alternating with vincristine + cyclophosphamide (CPM) 2 g/m(2)/d, for four cycles. Children with nongerminomatous tumors or with abnormal markers received doubled doses of cisplatin and CPM. For germinoma patients in complete response (CR), RT was decreased from 50.4 to 30.6 Gy. High-risk patients received neuraxis RT: 50.4 Gy local + 30.6 Gy neuraxis in CR; 54 Gy local + 36 Gy if less than CR. RESULTS: Of 12 germinoma patients, 4 had cerebrospinal fluid (CSF) human chorionic gonadotropin (HCG) 6.9-21 mIU/ml. Of 14 nongerminomatous patients, HCG in serum or CSF was >50 mIU/ml in 9, alpha-fetoprotein (AFP) abnormal in 9. Four germinoma patients attained CR, six PR, one SD, one not evaluable after resection. Two nongerminomatous patients had CR, three PR, three SD, one PD, four not evaluable after resection; one inadequately treated patient had progressive disease (PD). Both PD patients died; one SD patient died during a seizure. Eleven germinoma patients are PF at median 66 months; one patient in CR refused RT, had PD at 10 months, received RT, and was PF at 56 months. Eleven of 14 nongerminomatous patients were PF at median 58 months. CONCLUSION: Response (germinoma, 91%; nongerminomatous, 55%) and survival are encouraging after this regimen plus response-based RT.

Adolescent↗
PubMed2006

Immune reconstitution inflammatory syndrome in the CNS of HIV-infected patients.

OBJECTIVE: To describe challenges in diagnosis and management of patients with clinical syndromes of immune reconstitution inflammatory syndrome (IRIS) involving the CNS. METHODS: The authors describe three patients with clinically distinct neurologic manifestations of IRIS with HIV infection who presented as diagnostic and therapeutic challenges. RESULTS: One patient with cryptococcal meningitis developed acute cerebellitis with mass effect and brainstem compression. Corticosteroid therapy was associated with complete resolution of the cerebellar lesion but the patient developed VZV encephalitis. Another patient with progressive multifocal leukoencephalopathy developed subacute progression of focal neurologic deficits associated with contrast enhancing lesions on brain MRI. This patient had spontaneous resolution of the lesion but was left with residual deficits. One patient developed a progressive dementing syndrome and deterioration over several months resulting in coma during combination antiretroviral therapy. A brain biopsy in this latter patient showed massive infiltration of T lymphocytes predominantly of the CD8 subtype. This patient had a significant improvement with corticosteroids and change in antiretroviral regimen although she was left with residual cognitive impairment. CONCLUSIONS: Immune reconstitution inflammatory syndrome should be suspected in patients who show clinical or radiologic deterioration following initiation of antiretroviral therapy accompanied with improvement in CD4 cell count and viral load. Some patients may respond to a brief course of treatment with corticosteroids.

AIDS-Related Opportunistic Infections↗
PubMed2001

Stereoselective synthesis of chiral pinene[5,6]bipyridine ligands and their coordination chemistry.

The C(2)-symmetric chiral pinene[5,6]bipyridine V (Chart 1) was synthesized according to a procedure published by our group recently (Kolp, B.; Abeln, D.; Stoeckli-Evans, H.; Zelewsky, A. v. Eur. J. Inorg. Chem. 2001, 1207). A series of stereoselectively alkylated derivatives (Va-Vo) (Table 1) was prepared. The solid-state structures of the compounds Vc and Vk were determined by single-crystal X-ray diffraction, where both compounds show a transoid conformation of the bipyridine unit and proved to be alkylated stereoselectively from the sterically less hindered side of the pinene moiety. The X-ray structure of the cobalt complex 4 shows the metal ion to be tetrahedrally coordinated by one chiral bipyridine V and two chloride ligands. If 2 equiv of ligand V was used, 2:1 complexes were obtained with Cu(I), Ag(I), and Co(II) ions.

Journal Article↗
PubMed2001

Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells.

Amplification of the epidermal growth factor receptor (EGFR) gene is found in about 40% of glioblastomas (GBMs) but is rarely detected in GBM cell lines. We confirmed that the exceptional SKMG-3 GBM cell line retained amplified EGFR genes in vitro, and found that these sequences were concentrated on extra-chromosomal DNA particles similar to double-minute chromosomes. The cells contained two other gene mutations that are associated with high-grade astrocytic tumors: extra-chromosomal amplification of the cyclin-dependent kinase-4 (CDK4) gene and a homozygous mutation within the PTEN tumor suppressor gene. Immunoblots revealed very high levels of EGFR, moderately increased expression of CDK4, and no detectable PTEN protein. The overexpressed SKMG-3 EGFRs responded to exogenous ligand and resembled normal rather than mutant receptors. A heterozygous mutation of the p53 gene (p53R282W) correlated with failure of radiation to induce the expression of cyclin-dependent kinase inhibitor p21waf1 or an early G1 cell cycle arrest. Although each of these gene mutations occurs in GBMs, SKMG-3 cells had an unusual genotype in that a p53 gene mutation co-existed with amplified EGFR genes. Nonetheless, the SKMG-3 cell line can be exploited as a model to study how oncogenic EGFR signals in GBM cells interact with over-expressed CDK4 and loss of PTEN to confer the malignant phenotype.

Blotting, Southern↗
PubMed2001

Pleomorphic xanthoastrocytoma: favorable outcome after complete surgical resection.

To describe the clinical features, histologic characteristics, and management of patients with pleomorphic xanthoastrocytoma (PXA), we reviewed data on 13 children who had histologically confirmed PXA and were referred to the neuro-oncology service between 1985 and 1999. Neuro-imaging with CT and/or MRI documented the anatomic location, tumor extent, and degree of resection. There were 3 males and 10 females; median age was 12.9 years (range, 8.2-17.2 years). The most frequent presentations included seizures (n = 8) and headache (n = 5). Tumor sites included temporal (n = 5), parietal (n = 3), frontal (n = 1), frontoparietal (n = 1), parietooccipital (n = 1), and temporoparietal (n = 1) lobes and the spinal cord (n = 1). CT/MRI revealed a cystic component in 6 patients, with cyst wall enhancement in 3 patients. The solid component was uniformly enhancing in 11 patients. Vasogenic edema was present in 9 patients, and calcification was noted in 4 patients. Histopathologic findings included meningeal invasion in 12 patients, calcifications in 4, and necrosis in 2. Mitotic figures (1-12 per high-power field) were seen in 8 patients. Gross total resection was achieved in 8 patients, near total resection in 1, and subtotal resection in 4. Ten patients were alive with a median follow-up of 41 months at this writing. Two patients died of progressive disease, and 1 died of an unrelated cause. In conclusion, pleomorphic xanthoastrocytoma is a rare neoplasm in childhood, commonly presenting with seizures. Gross total resection without adjuvant therapy provides prolonged disease control, as seen in 6 of 7 patients (85%) in our series.

Adolescent↗
PubMed2000

Development of a beta-spectrometer using PIPS technology

Various anthropogenic sources contribute to the inventory of long live beta-emitters in the environment. Studies have been carried out to obtain the 90Sr distribution in environment in order to estimate its impact in terms of radiation exposure to humans. The Laboratory routinely measures 90Sr by proportional counter after radiochemistry. An incomplete radiochemical separation leads to a deposit submitted to count polluted by natural beta-emitters. In order to confirm the result, 90Y (daughter of 90Sr), is extracted from the final radiochemical fraction and counted. The 90Y decreasing (T(1/2) = 2.67 days) is checked by successive counts over 64 h. The delay between the end of radiochemistry and the counting is imposed by 15 days to allow radioactive equilibrium between 90Sr and 90Y to be established. In order to remove this delay the purity of the 90Sr fraction source can be verified by beta-spectrometry. Thus, a beta-spectrometer is under development in collaboration with Canberra Semi-Conductor and Canberra Electronic. It consists in a PIPS detector where several silicon layers are combined. Initial results will be presented in this paper.

Journal Article↗
PubMed1999

Reversion of human glioblastoma malignancy by U1 small nuclear RNA/ribozyme targeting of scatter factor/hepatocyte growth factor and c-met expression.

BACKGROUND: Expression of scatter factor (SF), also known as hepatocyte growth factor (HGF), and its receptor, c-met, is often associated with malignant progression of human tumors, including gliomas. Overexpression of SF/HGF in experimental gliomas enhances tumorigenicity and tumor-associated angiogenesis (i.e., growth of new blood vessels). However, the role of endogenous SF/HGF or c-met expression in the malignant progression of gliomas has not been examined directly. In this study, we tested the hypothesis that human glioblastomas can be SF/HGF-c-met dependent and that a reduction in endogenous SF/HGF or c-met expression can lead to inhibition of tumor growth and tumorigenicity. METHODS: Expression of the SF/HGF and c-met genes was inhibited by transfecting glioblastoma cells with chimeric transgenes consisting of U1 small nuclear RNA, a hammerhead ribozyme, and antisense sequences. The effects of reduced SF/HGF and c-met expression on 1) SF/HGF-dependent induction of immediate early genes (c-fos and c-jun), indicative of signal transduction; 2) anchorage-independent colony formation (clonogenicity), an in vitro correlate of solid tumor malignancy; and 3) intracranial tumor formation in immunodeficient mice were quantified. Statistical tests were two-sided. RESULTS: Introduction of the transgenes into glioblastoma cells reduced expression of the SF/HGF and c-met genes to as little as 2% of control cell levels. Reduction in c-met expression specifically inhibited SF/HGF-dependent signal transduction (P<.01). Inhibition of SF/HGF or c-met expression in glioblastoma cells possessing an SF/HGF-c-met autocrine loop reduced tumor cell clonogenicity (P =.005 for SF/HGF and P=.009 for c-met) and substantially inhibited tumorigenicity (P<.0001) and tumor growth in vivo (P<.0001). CONCLUSIONS: To our knowledge, this is the first successful inhibition of SF/HGF and c-met expression in a tumor model directly demonstrating a role for endogenous SF/HGF and c-met in human glioblastoma. Our results suggest that targeting the SF/HGF-c-met signaling pathway may be an important approach in controlling tumor progression.

Animals↗
PubMed1999

There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy.

PURPOSE: In June 1992, POG began accrual to a phase III study, POG-9239, designed to compare the time to disease progression, overall survival, and toxicities observed in children with newly diagnosed brainstem tumor treated with 100 mg/m2 of infusional cisplatin and randomized to either conventional vs. hyperfractionated radiotherapy. METHODS AND MATERIALS: Patients eligible for study were those between 3 and 21 years of age with previously untreated tumors arising in the pons. Histologic confirmation of diagnosis was not mandatory, provided that the clinical and MRI scan findings were typical for a diffusely infiltrating pontine lesion. Treatment consisted of a six-week course of local field radiotherapy with either once a day treatment of 180 cGy per fraction to a total dose of 5400 cGy (arm 1) or a twice a day regimen of 117 cGy per fraction to a total dose of 7020 cGy (the second of the three hyperfractionated dose escalation levels of POG-8495) (arm 2). Because of previously reported poor results with conventional radiotherapy alone, cisplatin was included as a potential radiosensitizer in an attempt to improve progression-free and ultimate survival rates. Based on results of the phase I cisplatin dose escalation trial, POG-9139, 100 mg/m2 was chosen for this trial and was delivered by continuous infusion over a 120-hour period, beginning on the first day of radiotherapy and repeated during weeks 3 and 5. One hundred thirty eligible patients were treated on protocol, 66 on arm 1 and 64 on arm 2. RESULTS: The results we report are from time of diagnosis through October 1997. For patients treated on arm 1, the median time to disease progression (defined as time to off study) was 6 months (range 2-15 months) and the median time to death 8.5 months (range 3-24 months); survival at 1 year was 30.9% and at 2 years, 7.1%. For patients treated on arm 2, the corresponding values were 5 months (range 1-12 months) and 8 months (range 1-23 months), with 1- and 2-year survival rates at 27.0% and 6.7%, respectively. Evaluation of response by MRI at 4 or 8 wks post treatment was available in 108 patients and revealed a complete response in 1 patient of each Rx arm, a partial response (> 50% decrease in size) in 18 patients of arm 1 and 15 patients of arm 2, minimal to no response (stable) in 25 patients of arm 1 and 23 patients of arm 2, and progressive disease in 13 patients of arm 1 and 12 patients of arm 2. The pattern of failure was local in all patients. Morbidity of treatment was similar in both Rx arms, with no significant toxicity (including hearing loss) reported. Autopsy was performed in 6 patients, and confirmed the presence of extensive residual tumor in these cases. CONCLUSION: The major conclusion from this trial is that the hyperfractionated method of Rx 2 did not improve event-free survival (p = 0.96) nor did it improve survival (p = 0.65) over that of the conventional fractionation regimen of Rx 1, and that both treatments are associated with a poor disease-free and survival outcome.

Adolescent↗
PubMed1999

Locally focused 3D coronary imaging using volume-selective RF excitation.

This paper describes a locally focused magnetic resonance (MR) imaging method for three-dimensional (3D) zonal echoplanar coronary angiography using volume-selective radiofrequency (RF) excitation. Spatially variable resolution was used for delineating coronary arteries and reducing the effect of residual signals caused by the imperfect excitation profile of the RF pulse. The use of variable resolution enabled the derivation of basis functions having different spatial characteristics pertaining to regional object details, and a significantly smaller number of phase-encoded signal measurements was needed for image reconstruction. Based on the relative significance of each required phase-encoding step, real-time phase-encode reordering was used to minimize the effect of respiratory motion during coronary imaging. To eliminate Nyquist ghosting in oblique echoplanar imaging, the echoplanar data acquired during forward and reverse echoes were reconstructed separately and then averaged with spatial registration for improving the signal-to-noise ratio. The technique was evaluated with phantom experiments and right coronary artery images of 11 asymptomatic volunteers using a 0.5 T MR system. A marked improvement in image quality has been achieved despite a 30% reduction in imaging time.

Artifacts↗
PubMed1999

Knowledge-based tensor anisotropic diffusion of cardiac magnetic resonance images.

We present a general formulation for a new knowledge-based approach to anisotropic diffusion of multi-valued and multi-dimensional images, with an illustrative application for the enhancement and segmentation of cardiac magnetic resonance (MR) images. In the proposed method all available information is incorporated through a new definition of the conductance function which differs from previous approaches in two aspects. First, we model the conductance as an explicit function of time and position, and not only of the differential structure of the image data. Inherent properties of the system (such as geometrical features or non-homogeneous data sampling) can therefore be taken into account by allowing the conductance function to vary depending on the location in the spatial and temporal coordinate space. Secondly, by defining the conductance as a second-rank tensor, the non-homogeneous diffusion equation gains a truly anisotropic character which is essential to emulate and handle certain aspects of complex data systems. The method presented is suitable for image enhancement and segmentation of single- or multi-valued images. We demonstrate the efficiency of the proposed framework by applying it to anatomical and velocity-encoded cine volumetric (4-D) MR images of the left ventricle. Spatial and temporal a priori knowledge about the shape and dynamics of the heart is incorporated into the diffusion process. We compare our results to those obtained with other diffusion schemes and exhibit the improvement in regions of the image with low contrast and low signal-to-noise ratio.

Algorithms↗
PubMed1998

[Cardiovascular arrest in adrenal cortex insufficiency].

We describe the case of a 55 year old patient with acute adrenal insufficiency who suffered from abdominal pain, recurrent syncope and cardiac arrest. 32 hours after the successful cardio-pulmonal resuscitation, the patient developed a catecholamine resistant hyperdynamic shock. With the initiation of prednisolone therapy, because of suspected acute adrenal insufficiency, catecholamines became effective and led to a hemodynamic stabilisation and a general amelioration of the patient. Glucocorticoids have a permissive function for catecholamines and therefore are essential in these situations. After fluid replacement acute adrenal insufficiency may present as hyperdynamic shock which can be confounded with septic shock. Cardiac arrest however is an unusual complication of Addison's disease and the responsible pathological mechanism is unknown.

Addison Disease↗
PubMed1998

Motion and deformation tracking for short-axis echo-planar myocardial perfusion imaging.

The assessment of regional myocardial perfusion during the first-pass of a contrast agent bolus requires tracking of the signal time course for each myocardial segment so that a detailed perfusion map can be derived. To obtain such a map in practice, however, is not trivial because deformation of the shape of the myocardium and respiratory-induced motion render a major difficulty in this process. This study describes an automated approach for motion and deformation tracking of functional myocardial perfusion images. The effectiveness of the described method has been evaluated using a numerical phantom and results are compared with those from existing techniques which use deformable models. Preliminary results from applying our approach to 20 patients are discussed and compared with those from SPECT studies.

Aged↗
PubMed1997

Automatic tracking of the aorta in cardiovascular MR images using deformable models.

We present a new algorithm for the robust and accurate tracking of the aorta in cardiovascular magnetic resonance (MR) images. First, a rough estimate of the location and diameter of the aorta is obtained by applying a multiscale medial-response function using the available a priori knowledge. Then, this estimate is refined using an energy-minimizing deformable model which we define in a Markov-random-field (MRF) framework. In this context, we propose a global minimization technique based on stochastic relaxation, Simulated annealing (SA), which is shown to be superior to other minimization techniques, for minimizing the energy of the deformable model. We have evaluated the performance and robustness of the algorithm on clinical compliance studies in cardiovascular MR images. The segmentation and tracking has been successfully tested in spin-echo MR images of the aorta. The results show the ability of the algorithm to produce not only accurate, but also very reliable results in clinical routine applications.

Algorithms↗
PubMed1996

A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain. CNS Cancer Consortium.

PURPOSE: This study was designed to evaluate strategies to overcome the resistance of anaplastic gliomas of the brain to external beam radiotherapy (ERT) plus carmustine (BCNU). Patients were > or = 15 years of age, had a histologic diagnosis of malignant glioma, and a Karnofsky performance status (KPS) > or = 60%. METHODS AND MATERIALS: In Randomization 1, patients were assigned to receive either ERT alone (61.2 Gy) or ERT plus mitomycin C (Mito, IV 12.5 mg/m(2)) during the first and fourth week of ERT. After this treatment, patients went on to Randomization 2, where they were assigned to receive either BCNU (i.v. 200 mg/m(2)) given at 6-week intervals or 6-mercaptopurine (6- MP, 750 mg/m(2) IV daily for 3 days every six weeks), with BCNU given on the third day of the 6-MP treatment. Three hundred twenty-seven patients underwent Randomization 1. One hundred sixty-four received ERT alone, and 163 received ERT + Mito [average 52.7 years; 63% male; 69% glioblastoma multiforme (GBM); 66% had a resection; 56% KPS > or = 90%]. Step-wise analysis of survival from Randomization 1 or 2 indicates that survival was significantly diminished by: (a) age > or = 45 years (b) KPS < 90%; (c) GBM/gliosarcoma histology; (d) stereotactic biopsy as opposed to open biopsy or resection. Median survival from Randomization 1 in both arms (ERT + Mito) was 10.8 months. Median survival from Randomization 2 was 9.3 months for BCNU/6MP vs. 11.4 months for the BCNU group (p = 0.35). Carmustine/6-MP showed a possible survival benefit for histologies other than GBM/GS. Two hundred and thirty-three patients underwent Randomization 2. The proportion of patients in the ERT group who terminated study prior to Randomization 2 was significantly less in the ERT group than in the ERT + Mito group (20 vs. 37%, p < 0.001). CONCLUSIONS: (a) The addition of Mito to ERT had no impact on survival; (b) patients treated with ERT + Mito were at greater risk of terminating therapy prior to Randomization 2; (c) there was not a significant survival benefit to the addition of 6-MP to BCNU.

Adult↗
PubMed1995

On the development of an interstitial radiation protocol for a multicenter consortium. Experience with permanent low-dose rate and temporary high-dose rate 125I implants in 'failed' and 'newly diagnosed' glioblastoma patients: quality assurance methodology and a possible future adjuvant for therapeutic enhancement.

Three interstitial implant trial groups (one permanent low-dose rate 125I and two temporary high-dose rate 125I implants) in glioblastoma patients ('newly diagnosed' and 'failed') were compared to non-randomized similar control groups for efficacy. The results formed the basis for the BTCG 87-01 national implant trial. The 'pilot' trial demonstrated: 1) the effectiveness of a temporary high-dose rate 125I implant in 'failed' and 'newly diagnosed' patients; 2) the ability of a multicenter consortium to adhere to a standard protocol; 3) a methodology to insure quality assurance; and 4) the possibility of the future adjuvant application of hyperthermia using a single catheter system.

Brain Neoplasms↗
PubMed1995

Assessment of magnetic resonance velocity mapping of global ventricular function during dobutamine infusion in coronary artery disease.

BACKGROUND: Magnetic resonance imaging (MRI) is a versatile technique for examination of the cardiovascular system but only recently has assessment of myocardial ischaemia in coronary artery disease (CAD) become possible, for example by demonstrating abnormalities of regional ventricular contraction during stress. Global ventricular function during stress was assessed by MRI of aortic flow, which has not been previously attempted. DESIGN: Variables measured by MRI reflecting the effect of ischaemia on global ventricular function during dobutamine stress were correlated with thallium-201 myocardial perfusion tomography. PATIENTS: 10 normal controls and 25 patients with CAD. SETTING: Tertiary cardiac referral centre. METHODS: Novel MRI sequences and analysis systems were used to measure the following variables during staged dobutamine infusion to 20 micrograms/kg/min: stroke volume, cardiac output, cardiac power output, peak flow, peak flow acceleration, aortic back flow, and flow wave velocity. Heart rate, blood pressure, double product, and maximum tolerated dobutamine dose were also measured. Multiple regression analysis was used to compare changes during stress with 201TI tomography. RESULTS: All parameters except for stroke volume and diastolic blood pressure increased in the controls. In the patients with CAD a significant relation was shown between the extent of reversible ischaemia and the change in peak flow acceleration (P < 0.00001), peak flow (P = 0.002), cardiac power output (P = 0.036), maximum dobutamine dose (P = 0.039), and systolic blood pressure (P = 0.04). Peak flow acceleration accounted for 58.4% of the variation in reversible ischaemia, and after allowing for this, only cardiac power output remained independently predictive adding a further 4.2% to the model (adjusted r2 = 0.626). A decrease in peak flow acceleration with an increase in dobutamine infusion indicated moderate or severe ischaemia (chi 2 = 10.2, P = 0.017). CONCLUSION: MRI may be used to assess variables of aortic flow during stress, which includes acceleration with high temporal resolution. Peak flow acceleration was the most sensitive indicator of the effect of ischaemia on global ventricular function.

Adult↗