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At least 775 records · Page 43Linked to original sources
PubMed1993

Severe corneoscleral infection. A complication of beta irradiation scleral necrosis following pterygium excision.

OBJECTIVE: To assess the precipitating factors, clinical course, and treatment of 11 cases of severe intraocular infections of radionecrosis after pterygium excision in an attempt to minimize the devastating ocular sequelae. DESIGN AND SETTING: From the database of cases of radionecrosis at Royal Perth (Australia) Hospital and Lions Eye Institute, Perth, we identified 11 cases of severe intraocular infection complicating radionecrosis. We reviewed the case notes and the available radiotherapy records (n = 8). PATIENTS: Eleven patients admitted during an 8-year period. RESULTS: Mean (+/- SD) dose of radiotherapy was 22.7 +/- 1.0 Gy and mean latency period, 14.45 +/- 2.5 years. Among the six proven bacterial cases, Pseudomonas was identified in four, Staphylococcus aureus in one, and Streptococcus pneumoniae was involved in one bilateral case. Among the four fungal cases, Petriellidium boydii was indicated in two, and Fusarium and Scedosporium inflatum in one each. The condition may remain undiagnosed for some time and mimic a posterior scleritis, serous retinal detachment, or pseudotumor. INTERVENTIONS: Early débridement and culture; close microbiological assistance; and systemic antimicrobials for a prolonged period. Perforation or incipient perforation necessitated penetrating keratoplasties in seven patients and repeated keratoplasties in three. MAIN OUTCOME MEASURES: The use of radiotherapy following pterygium excision should be limited and only low doses used. Ulcer beds and calcific plaques at sites of radionecrosis should not be directly covered without first performing adequate sterilization. Removal of plaques may precipitate sepsis; ulcer beds and plaques harbor infective agents. CONCLUSION: Severe radionecrosis may expose a patient to a lifelong risk of intraocular sepsis and profound visual morbidity. Conjunctival autografting is a safer method to reduce recurrence rate after pterygium excision.

Aged↗
PubMed2000

Acute myelogenous leukemia after exposure to strontium-89 for the treatment of adenocarcinoma of the prostate.

BACKGROUND: Strontium-89 is a pure Beta-emitting radioactive analogue of calcium that has been shown to be beneficial in the palliation of pain due to osseous metastases from adenocarcinoma of the prostate. The most significant reported toxicity is dose-related, reversible, myelosuppression characterized primarily by thrombocytopenia. METHODS: A report of two patients in whom acute myelogenous leukemia (AML) developed after treatment with strontium-89 and a review of the literature are presented. RESULTS: The two patients described in the current study developed AML 17 months and 26 months, respectively, after exposure to strontium-89 for the treatment of prostate carcinoma. To the authors' knowledge these patients represent the first two reported cases of AML after strontium-89 therapy for prostate carcinoma. CONCLUSIONS: The results of the current study suggest the leukemogenic potential of strontium-89 treatment in humans. To the authors' knowledge, the current study represents the first report of AML after therapeutic exposure to strontium-89. As this agent is used more frequently (and earlier in the disease course) in patients with prostate carcinoma, an increased incidence of secondary AML complicating the clinical management of patients with prostate carcinoma may be observed. [See editorial on pages 497-9, this issue.]

Adenocarcinoma↗
PubMed1998

Therapeutic efficacy and dose-limiting toxicity of Auger-electron vs. beta emitters in radioimmunotherapy with internalizing antibodies: evaluation of 125I- vs. 131I-labeled CO17-1A in a human colorectal cancer model.

Recent clinical results suggest that higher anti-tumor efficacy may be achieved with internalizing monoclonal antibodies (MAbs) at lower toxicity when labeled with Auger-electron, as compared to conventional beta-emitters. The aim of our study was to compare the toxicity and anti-tumor efficacy of the 125I-labeled internalizing MAb, CO17-1A, with its 131I-labeled form in a human colon cancer model in nude mice. Biodistribution studies were performed in nude mice bearing s.c. human colon cancer xenografts. For therapy, the mice were injected either with unlabeled 125I- or 131I-labeled C017-1A at equitoxic doses. Control groups were left untreated, were given a radiolabeled isotype-matched irrelevant antibody or a tumor-specific, but noninternalizing antibody. The maximum tolerated activities (MTD) of 131I-and 125I-CO17-1A without artificial support were 300 microCi and 3 mCi, respectively. Myelotoxicity was dose-limiting; bone marrow transplantation allowed for an increase of the MTD to 400 microCi of 131I-17-1A, whereas the MTD of 125I-17-1A with bone marrow support had not been reached at 5 mCi. Whereas no significant therapeutic effects were seen with unlabeled C017-1A, tumor growth was retarded with 131I-CO17-1A. With the 125I-label, however, therapeutic results were clearly superior. In contrast, no significant difference was observed in the therapeutic efficacy of the 131I- vs. 125I-labeled, noninternalizing antibodies. Our data indicate a superiority of Auger-electron emitters, such as 125I, as compared to therapy with conventional beta-emitters with internalizing antibodies. The lower toxicity of Auger emitters may be due to the short path length of their low-energy electrons, which can reach the nuclear DNA only if the antibody is internalized (as is the case in antigen-expressing tumor tissue, but not in the stem cells of the red marrow).

Animals↗
PubMed1975

Glycogen-rich adenocarcinoma of minor salivary glands. A light and electron microscopic study.

A malignant glycogen-rich adenocarcinoma of palatal salivary glands is reported. Histopathology revealed nonencapsulated nests and cords of polyhedral cells showing voluminous clear cytoplasms and cellular pleomorphisms, separated by fine vascular septae. Small and large ducts were infrequently seen showing apparent transition of large ducts into clear cells. The tumor cells were PAS- and Best-carmine positive, diastase soluble, and mucicarmine and Alcian-blue negative. Ultrastructurally, the tumor cells were arranged in solid nests and cords of electron-lucent cells surrounding single or multiple lumina, and surrounded by basement lamina. Occasional fusiform electron-dense cell processes were present beneath the basement lamina. The electron-lucent cells were joined by junctional complexes, contained intracytoplasmic canals, and were filled with massive accumulations of beta glycogen particles. The electron-dense processes contained interlacing whorls of fine filaments and exhibited peripheral focal densities. The findings suggest that this glycogen-rich malignant tumor is of epithelial origin most probably of ductal cells.

Adenocarcinoma↗
PubMed1994

Application of the cross-organ beta dose method for tissue dosimetry in tumor-bearing mice treated with a 90Y-labeled immunoconjugate.

BACKGROUND: Radioimmunotherapy of nude mice bearing human tumor xenografts using 90Y-labeled monoclonal antibodies has resulted in slower tumor growth, decreased tumor burden, and increased survival times. Dosimetry estimates in the murine model usually were based on biodistribution data and standard Medical Internal Radiation Dose approaches. A new dosimetric model for the mouse that takes into consideration the small dimensions, mass, and proximity of murine organs has been developed based on self-organ absorbed and cross-organ doses. METHODS: Nude mice bearing carcinoembryonic antigen-expressing WiDr human colon cancer xenografts were injected with 240 microCi 90Y-anti-carcinoembryonic-antigen monoclonal antibodies and then killed at 12, 24, 72, 120, and 168 hours. Tumors and major organs were removed, weighed, and counted on a gamma counter. Using the resulting biodistribution data, the radiation doses to tumor and normal organs were calculated using the new dosimetric model for the mouse. RESULTS: Three organs (the liver, kidneys, and large bowel) directly received > 50% of the total absorbed beta dose from radioactivity. Lungs, stomach, and marrow received the highest percentage (70-75%) of the total absorbed dose from adjacent organs. Tumor absorbed dose, estimated with the new dosimetric model, was three times less than that obtained with a MIRD-style calculation without correction for self-absorbed and cross-organ doses. CONCLUSIONS: The new dosimetric model, which accounts more accurately for self-organ absorbed and cross-organ beta dose fraction, allows the calculation of tumor and organ doses in the murine model. Accurate estimation of radiation doses to tumor and critical organs, such as the marrow, spleen and kidneys, is important in determining the efficacy and toxicity of radioimmunotherapy regimens in animals and in subsequent human applications.

Animals↗
PubMed2000

Modulation of daunorubicin cellular resistance by combination of P-glycoprotein blockers acting on drug efflux and intracellular drug sequestration in Golgi vesicles.

BACKGROUND: S9788 and PSC833 were developped as P-glycoprotein (Pgp) blockers and found to act additionally on daunorubicin subcellular distribution, involving different putative targets. On this basis, combinations of S9788 and PSC833 were evaluated in Pgp-expressing MCF7(DXR) cells in which we recently demonstrated that daunorubicin was sequestered in Golgi vesicles (Bour-Dill et al.: Cytometry, 39: 16-25, 2000). METHODS: Combinations of S9788 and PSC833 consisted in complementary fractions of iso-effective concentrations (IEC) leading to 90% (IEC90) and median (IEC50) reversion of daunorubicin resistance. Resistance modulation was assessed using cytotoxicity assays, flow cytometry determination of intracellular daunorubicin, and fluorescence microscopy analysis of daunorubicin subcellular distribution. RESULTS: Individually, both S9788 and PSC833 were found to be very potent with IEC90 of 5 and 15 micromol/l, and IEC50 of 0.1 and 0.2 micromol/l, respectively, for S9788 and PSC833. When combined, synergistic cytotoxicity was observed for both IEC90 and IEC50 combinations while intracellular daunorubicin fluorescence was only synergistically increased for IEC90 combinations. For IEC50 combinations, no increase in intracellular fluorescence was observed, and fluorescence microscopy examination of the cells suggested that daunorubicin sequestration in Golgi vesicles could be modulated at concentrations that do not significantly increase daunorubicin cellular concentration. Using immunofluorescence and reverse transcription-polymerase chain reaction analyses, multidrug resistance-associated protein, major vault lung-resistance protein, and anthracycline-resistance associated protein were not found to be implicated. CONCLUSIONS: Synergistic combinations of S9788 and PSC833 might offer alternative ways to decrease the toxicity generated by high-dose Pgp-blockers without altering the efficacy of the resistance modulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Encapsulation of isotope on novel beta-emitting poly(ethylene terephthalate) surfaces.

Recent data indicate that intravascular betaa-irradiation from centrally located sources at the time of balloon angioplasty or stenting reduces proliferation of smooth muscle cells, neointima formation, and restenosis. In an effort to simplify radiation delivery, a novel beta-radiation source was developed based on the adsorption of 32P (phosphoric acid) by pH-sensitive chitosan hydrogel on a poly(ethylene terephthalate) balloon surface. To prevent the 32P-isotope desorption in the patient's blood, the adsorbed phosphoric acid was precipitated as CaHPO4 on the surface by a saturated Ca(OH)2/5% CaCl2 solution. Various polyurethanes were applied to seal the radioactive surface by the dip-coating method. The isotope off-rate results were determined. Optimal results were obtained by serially coating with two polyurethane solutions. This approach holds promise for simplifying and improving the safety, and minimizing the cost of intravascular brachytherapy.

Adsorption↗