Influence of radiation dose reduction gloves on exposure parameters, entrance dose rates and eye doses of interventionalists during mobile C-arm fluoroscopic procedures: A phantom study.

INTRODUCTION: During fluoroscopic examinations, radiation dose reduction gloves (RRGs) protect the hands of the interventionalist against ionising scattered radiation from the patient. Some fluoroscopic procedures may require the hands of the interventionalist in the path of the primary X-ray beam. This study investigates the influence of RRGs in the field of view (FOV) on exposure parameters, entrance dose rates and eye doses of interventionalists during mobile C-arm fluoroscopic procedures. METHOD: Polymethylmethacrylate (PMMA) slabs were stacked on each other to simulate patient thicknesses. The abdomen protocol of the unit was selected for the study. The entrance dose rates to the surface of the PMMA slabs and the scattered radiation were measured for an undercouch configuration with and without RRGs in the FOV. The exposure parameters were noted. The scattered radiation for an overcouch configuration was measured. RESULTS: The entrance dose rate increases as the FOV decreases for a fixed thickness of PMMA. The presence of RRGs in the FOV increases the exposure parameters, entrance dose rates and the scattered radiation to the eyes of the interventionalist. For the first level of RRG coverage, percentage increases in entrance dose rates and eye doses for the 23 cm FOV for all thicknesses of PMMA slabs ranged from 1.0% to 17.0% and 20.0%-30.0%, respectively; for the second level of RRG coverage, the entrance dose rates ranged from 17.0% to 45.0% and the eye doses from 50.0% to 60.0%. Percentage increases depend on the FOV, the patient's thickness, and the size and orientation of the RRGs in the FOV. Scattered radiation to the eyes of the interventionalist increases with an overcouch configuration compared to an undercouch configuration. CONCLUSION: Sterile RRGs protects the hands of the interventionalist against scattered radiation. But in the FOV, they increase the scattered radiation to the personnel and the patient entrance dose rate. IMPLICATIONS FOR PRACTICE: For best practice in C-arm fluoroscopy-guided procedures, appropriate FOV and C-arm orientation should be selected, whilst RRGs should not be in the path of the primary beam unless necessary.

Current concepts for the surgical management of carotid body tumor.

BACKGROUND: Carotid body tumor (CBT) is a rare lesion of the neuroendocrine system. Chronic hypoxia has long been recognized as an etiology of CBT and other paragangliomas. Recent biogenetic discoveries reveal that mutations in oxygen-sensing genes are another etiology, accounting for approximately 35% of cases, and that these 2 etiologies are probably additive. DATA SOURCES: (1) A retrospective analysis of fifteen cases of CBT in a 6-year period occurring in the mountains of Southern Appalachia; (2) an extensive review of the literature on the surgery of CBT and on the expansive biogenetic understanding of the disease. CONCLUSIONS: Improved imaging, vascular surgical techniques, and understanding of the disease have vastly improved outcomes for patients. The necessities for long-term follow-up and appropriate genetic testing and counseling of patients and their families are documented. Surgeon and institutional competence are critical in achieving maximal outcomes.

Influence of DNA double-strand break rejoining on clonogenic survival and micronucleus yield in human cell lines.

PURPOSE: To examine the role of DNA double-strand break (DSB) rejoining in cell survival and micronucleus yield after 60Co gamma-irradiation. MATERIALS AND METHOD: Thirteen human cell lines (six glioblastoma, five prostate, one melanoma, one squamous cell carcinoma) were irradiated with 60Co gamma-rays to doses of 0-10Gy for cell survival and micronucleus measurements and 0-100Gy for DSB rejoining. Measurements were performed using standard clonogenic, micronucleus and constant-field gel electrophoresis assays. RESULTS: Radioresistance and micronucleus yield were positively correlated (r=0.74, p=0.004). A significant cell type-dependent correlation was demonstrated between total (0-20 h) DSB rejoining and cell survival (r=0.86, p=0.03 for glioblastomas; r=0.79, p=0.04 for other cell lines), with more resistant cell lines showing higher levels of DSB rejoining. No relationship was apparent between fast (0-2 h) or slow (2-20 h) DSB rejoining and clonogenic survival. While there was no relationship between total or slow DSB rejoining and micronucleus yield, a significant and cell type-specific correlation emerged between fast rejoining and micronucleus yield for the glioblastomas (r=0.89, p=0.04) and other cell lines (r=0.76, p=0.04). Cell lines with higher levels of DSB rejoining within 2 h of irradiation showed higher yields of micronuclei. CONCLUSION: Fast DSB rejoining, possibly through interaction with slow DSB rejoining, appears to play an important role in the formation of micronuclei. However, total DSB rejoining reflects intrinsic radiosensitivity. Consideration of differences in DSB rejoining kinetics might contribute to a better understanding of the significance of cell survival and micronucleus data in the clinical and radiation protection setting.

Radiosensitization and DNA repair inhibition by pentoxifylline in NIH3T3 p53 transfectants.

PURPOSE: To examine the role of p53 mutations in the modulation of DNA repair and radiotoxicity by pentoxifylline. MATERIALS AND METHODS: NIH3T3 murine cells transfected with mutant p53 constructs were examined for the influence of pentoxifylline on radiotoxicity to Co(60) gamma-irradiation by colony assay. DNA repair (0-100 Gy) was measured by constant-field gel electrophoresis. Apoptosis was assessed by flow cytometry with the annexin-V-binding assay. RESULTS: In the two p53 hot-spot mutant cell lines p53-S269R and p53- + 15, the SF(10) radiotoxicity enhancement factors induced by the pentoxifylline were 8.0 and 9.7, respectively. In the p53 deletion mutant p53-DeltaA cell line, the radiotoxicity enhancement factor was 2.6. No radiosensitization was obtained in the untransfected p53 wild-type cell line U-Wt and in the transfected p53 double-wild-type p53-Wt cell line. When pentoxifylline was added after irradiation at the time of maximum G2 block expression, no radiosensitization was observed in any of the five cell lines. Constant-field gel electrophoresis analyses after 20 h of repair showed that pentoxifylline suppresses DNA double-strand break repair in all p53 mutant cell lines, as indicated by repair inhibition factors of 2.0-2.3. No repair suppression was found in the p53 wild-type cell lines. CONCLUSIONS: p53 mutations are a general requirement for radiosensitization by pentoxifylline and the level of radiosensitization depends upon the location of the p53 mutation.

Influence of pentoxifylline, A-802710, propentofylline and A-802715 (Hoechst) on the expression of cell cycle blocks and S-phase content after irradiation damage.

The toxicity of the five methylxanthine derivatives, caffeine, pentoxifylline, A802710, propentofylline and A802715, was determined against the two human melanoma lines, Be11 and MeWo, and against the two human squamous cell carcinoma lines, 4197 and 4451, by vital dye staining assay. Pentoxifylline and A802710 emerge as the least toxic showing TD(50) (toxic dose of 50%) levels of 3.0-4.0 mM. Propentofylline and caffeine take an intermediate position. A802715 has a TD(50) of 0.9-1.1 mM and is the most toxic. Subtoxic concentrations (

The role of G2-block abrogation, DNA double-strand break repair and apoptosis in the radiosensitization of melanoma and squamous cell carcinoma cell lines by pentoxifylline.

PURPOSE: To examine the role of G2-block abrogation, DNA repair inhibition and apoptosis in the enhancement of radiotoxicity by pentoxifylline. MATERIALS AND METHODS: The influence of pentoxifylline on radiotoxicity was assessed by colony assay in TP53 wild-type Bell and mutant MeWo melanoma, and in TP53 wild-type 4197 and mutant 4451 squamous cell carcinoma (SCC) cell lines. G2-block abrogation was assessed by flow cytometry. Induction of DNA damage and repair was measured over a dose range of 0-100 Gy by constant field gel electrophoresis (CFGE). The Annexin-V binding assay was used to identify apoptotic cells. RESULTS: Pentoxifylline, when combined with irradiation, significantly increased radiotoxicity in the TP53 mutant MeWo and 4451 cell lines by radiotoxicity enhancement factors of 3 and 14.5 respectively. No radiosensitization was seen in the TP53 wild-type Be11 and 4197 cells. When the drug was added after irradiation at the time of maximum G2-block expression, no radiosensitization was seen in any of the four cell lines. CFGE analyses showed that pentoxifylline effectively suppressed DNA double-strand break (DSB) repair in all four cell lines, as indicated by 20 h repair inhibition factors of 1.4-2.4. Pentoxifylline did not increase apoptosis in any of the four cell lines. CONCLUSION: These data suggest that radiosensitization by pentoxifylline is not a consequence of G2-block abrogation alone, but that inhibition of DSB repair plays a role in certain cell types.

A comparison of the potential therapeutic gain of p(66)/Be neutrons and d(14)/Be neutrons.

PURPOSE: To determine the relationship between photon sensitivity and neutron sensitivity and between neutron RBE and photon resistance for two neutron modalities (with mean energies of 6 and 29 MeV) using human tumor cell lines spanning a wide range of radiosensitivities, the principal objective being whether or not a neutron advantage can be demonstrated. METHODS AND MATERIALS: Eleven human tumor cell lines with mean photon inactivation doses of 1.65-4. 35 Gy were irradiated with 0-5.0 Gy of p(66)/Be neutrons (mean energy of 29 MeV) at Faure, S.A. and the same plating was irradiated on the same day with 0-10.0 Gy of Cobalt-gamma-rays. Twelve human tumor cell lines, many of which were identical with the above selection, and spanning mean photon inactivation doses of 1.75-4.08 Gy, were irradiated with 0-4 Gy of d(14)/Be neutrons (mean energy of 6 MeV) and with 0-10 Gy of 240 kVp X-rays at the Essen Klinikum. Cell survival was determined by the clonogenic assay, and data were fitted to the linear quadratic equation. RESULTS: 1. Using the mean inactivation dose, a significant correlation was found to exist between neutron sensitivity and photon sensitivity. However, this correlation was more pronounced in the Faure beam (r(2) = 0.89, p

Influence of the G2 cell cycle block abrogator pentoxifylline on the expression and subcellular location of cyclin B1 and p34cdc2 in HeLa cervical carcinoma cells.

The progression of cells from G2 into mitosis is mainly controlled by formation of the cyclin B1/p34cdc2 complex. The behaviour of this complex in the irradiation-induced G2 cell cycle delay is still unclear. A prior study demonstrated that the expression of the cyclin B1 protein is reduced by irradiation, and restored to control levels by the methylxanthine drug pentoxifylline, which is a potent G2 block abrogator. The present study shows that irradiation, and 2 mM pentoxifylline affect the expression of the cyclin-dependent kinase p34cdc2 in HeLa cells. Irradiation induces p34cdc2 levels to increase and cyclin B1 levels to decrease. Addition of pentoxifylline at the G2 maximum reverses these trends. This is also evident from the cyclin B1/p34cdc2 ratios which decline after irradiation and are rapidly restored to control levels upon addition of pentoxifylline. It is concluded that cyclin BI and p34cdc2 protein expression are important events and act in concert to control the irradiation induced G2 block. Analysis of cyclin B1 expression in whole cells and in isolated nuclei furthermore show that cyclin B1 is translocated from the nucleus into the cytoplasm when the G2 block is abrogated by pentoxifylline.

Cyclin B1 expression in response to abrogation of the radiation-induced G2/M block in HeLa cells.

The G2 block is a major response of cells to DNA damage and seem to be induced independently of p53 status. It is thought that the G2 block has a protective function and allows cells to repair their DNA. The molecular events involved in the formation of the G2 block therefore are of great interest. We have used pentoxifylline, a potent G2 delay abrogator, to study the expression of an essential component of the mitosis promoting complex (MPF), cyclin B1. Cyclin B1/G2 ratios are used to show that irradiation induces a decrease in cyclin B1 expression and that pentoxifylline restores cyclin B1 expression to control level. This confirms that suppression of cyclin B1 plays a role in the formation of the G2 cell cycle delay, and that elevating cyclin B1 expression is part of the mechanism of action of pentoxifylline on G2 blocked cells.

The merits of cell kinetic parameters for the assessment of intrinsic cellular radiosensitivity to photon and high linear energy transfer neutron irradiation.

PURPOSE: Differences in tumor response and intrinsic cellular radiosensitivity make the selection of patients for specific radiation modalities very difficult. The reasons for these differences are still unclear, but are thought to be due to genomic and cellular characteristics. Because radiosensitivities vary between cell cycle stages and because S phase cells are very radioresistant, cell cycle kinetic parameters could be a candidate for predicting intrinsic radiosensitivity. METHODS AND MATERIALS: A panel of 15 tumor cell lines was analyzed for S phase content and potential doubling times (Tpot), and the influence of these parameters on the intrinsic radiosensitivity to 60Co gamma- and p(66)/Be neutron irradiation was assessed. RESULTS: S phase content and Tpot show a statistically significant correlation with the mean inactivation dose for photons. The correlation between cell kinetic parameters and the mean inactivation dose for neutrons showed the same trend as photon sensitivity but this was not found to be statistically significant. CONCLUSIONS: S phase content and Tpot were identified as suitable criteria for predicting photon sensitivity. It is suggested that cell kinetic parameters could play a role in identifying neutron sensitive tumors if both tumor and normal cells are analyzed.

Radiosensitivity variations in human tumor cell lines exposed in vitro to p(66)/Be neutrons or 60Co gamma-rays.

BACKGROUND: Neutron therapy should be beneficial to patients with tumor types which are resistant to photons but relatively sensitive to high-LET radiation. In this work the potential therapeutic gain of a clinical neutron beam is evaluated by quantifying the variations in radiosensitivity of different cell lines to neutrons and photons. MATERIAL AND METHODS: Different cell lines were exposed in vitro to p(66)/Be neutrons or 60Co gamma-rays. Micronuclei frequencies in binucleated cells and surviving fractions were determined for each cell type. RESULTS: Following exposure to either 1 or 1.5 Gy neutrons, micronuclei frequencies were significantly correlated with that observed for 2 Gy photons. A weak but significant correlation between the variation in neutron RBE values, determined from survival curve inactivation parameters and the mean inactivation doses for photon exposures, was also established. CONCLUSION: It is concluded that although neutron and photon sensitivities are related, the use of this high energy neutron source may constitute a potential therapeutic gain for tumor types that can be identified as very resistant to photons. Considering that a definitive oxygen gain factor has been established for this neutron beam the observed therapeutic gain is expected to be further enhanced in tumors where hypoxia protects cells from conventional radiation damage.