We have used photodynamic therapy (PDT) in the treatment of 56 patients with recurrent supratentorial gliomas who had failed radiation therapy and who were candidates for palliative reoperation. There were 34 males and 22 females; their mean age was 41 years and the mean Karnofsky score was 79. Thirty-two patients had glioblastoma multiforme (GBM), 14 had malignant astrocytoma (MA), 6 had malignant mixed glioma (MM), and 4 had ependymoma (EP). Porphyrin photosensitizer was administered intravenously (i.v.) 12-36 hours prior to photoillumination. All patients had the recurrent tumor subtotally resected or cyst drained at surgery followed by intraoperative cavitary photoillumination. In 15 cases interstitial photoillumination using fibers with 2 cm diffusing tips supplemented the cavitary illumination. The total light energy delivered ranged from 440 to 4,500 Joules (J) (median = 1,800 J). The energy administered ranged from 120 to 150 J per fiber and the linear energy density ranged from 65 to 450 J/cm. The energy density ranged from 8 to 110 J/cm2 (median = 38 J/cm2). There were two postoperative deaths and three patients were left with a persistent increase in their postoperative neurological deficit. The post-PDT median survival of patients with recurrent GBM was 30 weeks with a 1- and 2-year actuarial survival of 18% and 0%, respectively. The median survival of patients with recurrent GBM from first diagnosis was 118 weeks with a 1- and 2-year actuarial survival of 82% and 57%, respectively. The post-PDT median survival of patients with recurrent MA was 44 weeks with a 1- and 2-year actuarial survival of 43% and 36%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

PubMedDate not supplied

Protein tyrosine kinase inhibitors decrease lipopolysaccharide-induced proinflammatory cytokine production in mixed glia, microglia-enriched or astrocyte-enriched cultures.

Proinflammatory cytokines, tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6), produced by glial cells have been implicated in the neuropathogenesis of various diseases. However, the signal transduction pathway(s) for the production of these cytokines in glial cells are not well understood. This study examined the effects of two potent protein tyrosine kinase inhibitors, genistein and tyrphostin A25, on lipopolysaccharide (LPS)-induced production of TNF alpha, IL-1 alpha, and IL-6 in mouse primary mixed glia, microglia- or astrocyte-enriched cultures. LPS dose-dependently increased the production of TNF alpha, IL-1 alpha, and IL-6 from the mixed glia cultures. Genistein or tyrphostin A25 significantly inhibited the LPS-induced production of these cytokines. The LPS-induced TNF alpha, IL-1 alpha, and IL-6 production in microglia- or astrocyte-enriched cultures were also inhibited by tyrphostin A25. These results demonstrate that protein tyrosine kinases are involved in the signaling events of the LPS-induced production of TNF alpha, IL-1 alpha, or IL-6 in microglia or astrocytes, which may provide insights into therapeutic interventions in the pathway for cytokine production in the brain.

Animals↗

PubMedDate not supplied

Photodynamic therapy for the treatment of metastatic lesions in bone: studies in rat and porcine models.

This study represents the first reported use of photodynamic therapy (PDT) for metastatic bone lesions and specifically, as a treatment for spinal metastases. A model of bone metastasis in rat confirmed the efficacy of benzoporphyrin derivative-monoacid-mediated PDT for treating lesions within the spine and appendicular bone. Fluorimetry confirmed the selective accumulation of drug into the tumor(s) at 3 h post-injection. 48 h post-light delivery into the vertebral body of the rat spine loss of bioluminescent signal and histological analyses of sectioned spine confirmed MT-1 tumor cell kill in vivo as previously confirmed in vitro using an established cell viability assay. Porcine vertebrae provided a model comparable to that of human for light propagation and PDT response. Histological examination of vertebrae 48 h post-PDT revealed a necrotic radius of 0.6 cm with an average fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident up to 2 cm out from the treatment fiber. Results support the application of PDT to the treatment of primary or metastatic lesions within bone.

Animals↗

PubMedDate not supplied

A Monte Carlo model for the absorption and flux distributions of light in tissue.

A Monte Carlo computer model has been developed to study the propagation of light in tissues. Light attenuation is assumed to result from absorption and isotropic scattering. The model has been used to predict the distribution of absorbed dose in homogeneous tissues of different absorption/scattering ratios, for illumination both by external light beams and via implanted optical fibers. The photon flux into optical fibers placed in the tissue as detectors has also been investigated. The results are interpreted in relation to the use of visible light irradiation for photo radiation therapy.

Computers↗

PubMedDate not supplied

Calculation of radiation doses for nonuniformity distributed beta and gamma radionuclides in soft tissue.

In cancer radioimmunotherapy nonuniform distributions of radionuclides in geometrically irregular tumor volumes will be encountered. If the tumor is surrounded by a homogeneous layer of soft tissue, the radiation dose distribution in the tumor due to a beta-emitting nuclide can be calculated by convolution of the appropriate Loevinger's point source dose function, J, with the nuclide concentration distribution. Computer programs using fast Fourier transform techniques have been developed to evaluate the three-dimensional spatial convolution accurately and efficiently. Equivalent techniques have also been applied to gamma-emitting nuclides by replacing J in the convolution by the photon point isotropic specific absorbed fraction. Illustrative results are presented for the radiation dose distribution in a 1-ml target volume with activity distribution which is (i) uniform, (ii) limited by diffusion into the target volume, or (iii) limited by diffusion and shedding of radionuclide in the peripheral layers of the target volume. Calculations for the three cases are presented for 32P, 131I, and 15-, 30-, and 100-keV photon emitters.

Antibodies, Monoclonal↗

PubMedDate not supplied

Accuracy of blood transit time estimates using temporal filtering in digital radiology.

The application of recursive filtering in digital radiology can yield incorrect blood flow estimates if blood flow is calculated using a transit time, defined as the difference in times to peak contrast over the length of a vessel segment. The transit time error is calculated here, from computer simulations, as a function of filter design, image noise and contrast medium dispersion over the vessel segment. An error reduction procedure based on prefiltering is suggested and tested by simulation. Results indicate that the transit time error can be substantial and the reduction procedure effective, depending on the filter design and system noise level.

Angiography↗

PubMedDate not supplied

Total attenuation coefficients and scattering phase functions of tissues and phantom materials at 633 nm.

Measurements have been made of the total attenuation coefficient sigma t and the scattering phase function, S(theta), of 632.8 nm of light for a number of animal model tissues, blood, and inert scattering and absorbing media. Polystyrene microspheres of known size and refractive index, for which sigma t and S(theta) can be calculated by Mie theory, were used to test the experimental methods. The purpose of the study was to define typical ranges for these optical properties of tissues, as a contribution to the development of experimental and theoretical methods of light dosimetry in tissue, particularly related to photodynamic therapy of solid tumors. The results demonstrate that, for the representative tissues studied, the total attenuation coefficients are of the order of 10-100 mm-1, and that the scattering is highly forward peaked, with average cosine of scatter in the range 0.6-0.97.

Adipose Tissue↗

PubMedDate not supplied

Nontraumatic subluxation of the atlantoaxial joint: Grisel's syndrome.

Grisel's syndrome is defined as subluxation of the atlantoaxial joint not associated with trauma or bone disease. Primarily an affliction of children, the disorder may occur in association with any condition that results in hyperemia and pathologic relaxation of the transverse ligament of the atlantoaxial joint, including several common otolaryngic entities. Grisel's syndrome has been noted infrequently in the otolaryngologic literature; this paper reports a case from West Virginia University Hospital of a 6-year-old boy with radiographic evidence of retropharyngeal cellulitis following meningitis progressing to atlantoaxial subluxation. Discussed are the pathophysiologic aspects of Grisel's syndrome with an anatomic explanation recently described to account for the syndrome.

Atlanto-Axial Joint↗