The effect of gamma irradiation on anterior cruciate ligament allograft biomechanical and biochemical properties in the caprine model at time zero and at 6 months after surgery

BACKGROUND: High levels of gamma irradiation are required to eliminate the risk of bacterial and viral transmission during implantation of musculoskeletal allografts. The effects of high levels of gamma irradiation on anterior cruciate ligament allograft biomechanics are still not known. HYPOTHESIS: High-dose gamma irradiation (4 Mrad) adversely affects anterior cruciate ligament allograft biomechanics at surgery and at 6 months after surgery and affects biochemistry at 6 months. STUDY DESIGN: Controlled laboratory study. METHODS: Bilateral anterior cruciate ligament reconstructions were performed in 18 adult goats, with one knee receiving an irradiated patellar tendon allograft (4 Mrad) and the other receiving a frozen control allograft (0 Mrad). In 6 recipients (time zero group), graft pairs were tested immediately after sacrifice, and load relaxation of the femur-allograft-tibia preparation was measured during cyclic anterior displacement. Twelve recipients received bilateral anterior cruciate ligament reconstructions, staged 2 months apart, and were sacrificed a mean of 6 months postoperatively. Load relaxation and tensile failure testing were performed, followed by allograft biochemistry assessment. RESULTS: At time zero, irradiated grafts showed less load relaxation than did contralateral controls, but by 6 months, the trend had reversed because of decreases in control graft relaxation, with no changes in irradiated graft relaxation. By 6 months, irradiated grafts showed lower stiffness and maximum force compared to controls but no differences in modulus, maximum stress, or biochemistry. CONCLUSION: High levels of gamma irradiation affect anterior cruciate ligament allograft subfailure viscoelastic and structural properties but not material or biochemical properties over time. CLINICAL RELEVANCE: Although high levels of gamma irradiation may inactivate infectious agents, this treatment is not a feasible clinical option because of altered allograft biomechanics.     

The effect of contrast dose,imaging time,and lesion size in the MR detection of intracerebral metastasis.

PURPOSETo evaluate the effect of MR contrast dose versus delayed imaging time on the detection of metastatic brain lesions based on lesion size.METHODSContrast MR examinations with gadoteridol were obtained in 45 patients with brain metastases. The patients were divided into two groups: 16 received cumulative standard dose (0.1 mmol/kg) and 29 received cumulative triple dose (0.3 mmol/kg). Both groups were evaluated at two dose levels (lower dose and higher dose) with two separate injections. Each patient received an initial bolus injection of either 0.05 (cumulative standard dose) or 0.1 (cumulative triple dose) mmol/kg of gadoteridol to reach the lower-dose level and underwent imaging immediately and 10 and 20 minutes later. Thirty minutes after injection, an additional bolus injection of 0.05 (cumulative standard dose) or 0.2 (cumulative triple dose) mmol/kg was administered to reach the cumulative higher-dose level (cumulative standard dose, 0.1 mmol/kg; cumulative triple dose, 0.3 mmol). Images were acquired immediately.RESULTSThere was no difference in the detection rate for lesions larger than 10 mm among T2-weighted, lower-dose immediate and delayed, or immediate higher-dose images in both study groups. Lesions smaller than 10 mm had improved detection with delayed imaging in both study groups; however, the immediate higher-dose studies still had the highest detection rate.CONCLUSIONIn the evaluation of small central nervous system metastases, either delayed imaging after the injection of standard contrast dose or higher contrast dose may improve their detection, and therefore affect clinical management. Higher contrast dose (cumulative triple dose) studies appear to be more effective than delayed imaging with standard dose.     

重组人铜锌超氧化物歧化酶对小鼠骨髓造血粒─巨系祖细胞的辐射防护作用

目的：探讨重组人铜锌超氧化物歧化酶（ｒｈＣｕＺｎＳＯＤ）的辐射防护作用及其机理。方法：通过γ线辐射损伤小鼠的体内和体外实验，观察了ｒｈＣｕＺｎＳＯＤ和聚乙二醇修饰的ｒｈＣｕＺｎＳＯＤ（ＰＥＧ－ｒｈＣｕＺｎＳＯＤ）对小鼠骨髓造血粒－巨系祖细胞克隆产生率（ＣＦＵ－ＧＭ）的影响。结果：体内实验，小鼠整体照射，静脉给药，以上两种酶（２５`０～３００ｍｇ／ｋｇ）均能非常显著地提高ＣＦＵ－ＧＭ的数量。其中以照射前后联合给药效果最好。而单纯照射前给药，ｒｈＣｕＺｎＳＯＤ仅在照前１小时给药效果较好；ＰＥＧ－ｒｈＣｕＺｎＳＯＤ则在照前３小时或照前１小时给药都有较好的效果。体外实验，小鼠离体细胞照射并给药，未见ｒｈＣｕＺｎ－ＳＯＤ对ＣＦＵ－ＧＭ的影响。结论：以上两种酶对小鼠骨髓ＣＦＵ－ＧＭ有良好的辐射防护作用，其机理可能是通过机体防御系统作用的间接途径实现的。ＰＥＧ－ｒｈＣｕＺｎＳＯＤ的生物半衰期较长，可增加给药时机，因而具有更大的实用价值。     

Effect of MR imaging on spleen colony formation following gamma irradiation

This article describes experiments performed to examine the possible effect of interaction between ionizing radiation and magnetic resonance (MR) on damage to normal tissue. Eight-week-old ICR male mice were irradiated (cobalt-60 radiation) with 5, 6, or 7 Gy given either alone or followed by MR imaging. Other groups received fractionated doses of 6 Gy (3 Gy + 3 Gy) or 7 Gy (3 Gy + 4 Gy) either with or without subsequent MR imaging. Ten days after exposure, spleens were assayed for endogenous spleen colonies. The number of spleen colonies was lower at higher radiation doses, and fractionation of the dose resulted in an increase in colony number compared with a comparable dose in a single exposure. No difference was seen, however, between comparable radiation groups that were or were not subjected to MR imaging. In addition to the spleen colony assay, body weights and wet weights for spleen, thymus, and testes were obtained, since these suffer weight loss in proportion to radiation dose. As with the spleen colony assay, no significant effect of MR imaging was observed. These results indicate that for the normal tissues studied, MR imaging neither increases radiation damage nor inhibits repair between fractions.     

Relationships between colony forming efficiency and parameters of intrinsic radiosensitivity

Purpose: In an attempt to determine whether radiosensitivity is correlated with colony forming efficiency (CFE), a large amount of data have been analysed from the literature. Materials and methods: The survival curves of 446 human cell lines irradiated in exponentially growing phase in vitro are included in this study. Technical factors such as culture type and the use of feeder cells were considered cofactors in addition to the genetic and histological origin of the cells. Intrinsic radiosensitivity is expressed in terms of the parameters of the linear quadratic model and the single-hit multitarget model. Results: It is shown that low CFE is characteristic of cells plated in agar and cells from primary biopsies. Cells plated in the presence of feeder cells have, in general, higher CFE than cells plated without feeder cells. A positive correlation is observed between intrinsic radiosensitivity and CFE: the higher the CFE, the more resistant the cell line. This relationship is particularly obvious when radiosensitivity is expressed in terms of alpha, S 2 or D, parameters which essentially characterize the initial part of the survival curve. The correlation is also found within histological or genetic groups of cell lines. However, for a given cell line, there is no relationship between CFE and radiosensitivity among different experiments. Cells irradiated in the presence of feeder cells are less subject to this behaviour. Conclusions: CFE as well as radiosensitivity are intrinsic properties of a cell line. Experimental conditions determine the quality of the correlation between radiosensitivity and CFE.     

The effect of pelvic irradiation on ileal function.

Thirty-three patients with gynecological neoplasms undergoing radiotherapy to the pelvis had cholyl[1-14C]glycine breath tests to assess ileal function. Breath tests were performed on each patient in the first and fifth weeks of treatment and 19 of the patients had a third test three months post-treatment. In the first test, 29.9+/-16.8% (mean+/-SD) of the administered dose was excreted in breath 14C in 24 hours. This rose to 47.3+/-15.9% (t=6.08; p less than .001) in the fifth week and fell to 36.6+/-16% (t=2.29; p less than .05) at three months post-treatment. Eight patients had breath tests performed one year post-treatment and the test percentages were 32.7+/-7.8% (t=1.19; p less than .10). The increase in 14CO2 excretion in the fifth week of treatment occurred at a time when most patients were having diarrhea. The data suggest that bile acid malabsorption due to ileal dysfunction may be a factor in radiation-induced diarrhea which occurs in nearly all patients during pelvic irradiation.     

Relationships between colony forming efficiency and parameters of intrinsic radiosensitivity.

PURPOSE: In an attempt to determine whether radiosensitivity is correlated with colony forming efficiency (CFE), a large amount of data have been analysed from the literature. MATERIALS AND METHODS: The survival curves of 446 human cell lines irradiated in exponentially growing phase in vitro are included in this study. Technical factors such as culture type and the use of feeder cells were considered cofactors in addition to the genetic and histological origin of the cells. Intrinsic radiosensitivity is expressed in terms of the parameters of the linear quadratic model and the single-hit multitarget model. RESULTS: It is shown that low CFE is characteristic of cells plated in agar and cells from primary biopsies. Cells plated in the presence of feeder cells have, in general, higher CFE than cells plated without feeder cells. A positive correlation is observed between intrinsic radiosensitivity and CFE: the higher the CFE, the more resistant the cell line. This relationship is particularly obvious when radiosensitivity is expressed in terms of alpha, S2 or D, parameters which essentially characterize the initial part of the survival curve. The correlation is also found within histological or genetic groups of cell lines. However, for a given cell line, there is no relationship between CFE and radiosensitivity among different experiments. Cells irradiated in the presence of feeder cells are less subject to this behaviour. CONCLUSIONS: CFE as well as radiosensitivity are intrinsic properties of a cell line. Experimental conditions determine the quality of the correlation between radiosensitivity and CFE.     

Murine haemopoietic stem cells with long-term engraftment and marrow repopulating ability are more resistant to gamma-radiation than are spleen colony forming cells.

The radiation sensitivity of various subsets in the haemopoietic stem cell hierarchy was defined using a limiting dilution type long-term bone marrow culture technique that was previously shown to allow quantification of cells with spleen colony-forming potential (day-12 CFU-S) and in vivo marrow repopulating ability (MRA). Primitive stem cells that generate new in vitro clonable colony-forming cells (CFU-C) in the irradiated marrow (MRA) and have long-term repopulation ability (LTRA) in vitro (cobblestone area forming cell, CAFC day-28) had D0 values of 1.25 and 1.38 Gy, respectively. A lower D0 was found for the less primitive CFU-S day-12, CAFC day-12 and cells with erythroid repopulating ability (0.91, 1.08 and 0.97 Gy, respectively). CFU-S day-7 were the most radiosensitive (D0 equalling 0.79 Gy), while CFU-C and CAFC day-5 were relatively resistant to irradiation (D0 1.33 and 1.77 Gy). Split-dose irradiation with a 6 h interval gave dose sparing for stem cells with MRA and even more with in vitro LTRA, less for CFU-S day-12 and CAFC day-10 and none for CFU-S day-7. The cell survival data of the specified stem cell populations were compared with the ability of a fixed number of B6-Gpi-1a donor bone marrow cells to provide for short- and long-term engraftment in single- and split-dose irradiated congenic B6-Gpi-1b mice. Serial blood glucose phosphate isomerase (Gpi) phenotyping showed less chimerism in the split as compared to the single radiation dose groups beyond 4 weeks after transplant. Radiation dose-response curves corresponding to stable chimerism at 12 weeks for single and fractionated doses revealed appreciable split-dose recovery (D2-D1) in the order of 2 Gy. This was comparable to D2-D1 estimates for MRA and late-developing CAFC (1.27 and 1.43 Gy, respectively), but differed from the poor dose recovery in cells corresponding to the committed CFU-S day-7/12 and CAFC day-10 population (0.14-0.33 Gy). These data are together consistent with differential radiosensitivity and repair in the haemopoietic stem cell hierarchy, and provide a cellular basis for explaining the dose-sparing effect of fractionated total-body irradiation conditioning on long-term host marrow repopulation.     

The effect of lung volume on nodule size on CT

RATIONALE AND OBJECTIVES: We sought to determine how measures of nodule diameter and volume on computed tomography (CT) vary with changes in inspiratory level. MATERIALS AND METHODS: CT scans were performed with inspiration suspended at total lung capacity (TLC) and then at residual volume (RV) in 41 subjects, in whom 75 indeterminate lung nodules were detected. A fully automated contouring program was used to segment the lungs; followed by segmentation of all nodules and the corresponding lobe using semiautomated contouring in both TLC and RV scans. The percent changes in lung and lobar volumes between TLC and RV were correlated with percent changes in nodule diameters and volumes. RESULTS: Both nodule diameter and volume varied nonuniformly from TLC to RV-some nodules decreased in size, while others increased. There was a 16.8% mean change in absolute volume across all nodules. Stratified by size, the mean value of the absolute percent volume changes for nodules > or =5 mm and <5 mm were not significantly different (P = .26). Stratified by maximum attenuation, the mean value of the absolute percent volume changes between the TLC and RV series for noncalcified (17.7%, SD = 13.1) and completely calcified nodules (8.6% SD = 5.7) were significantly different (P < .05). CONCLUSION: Significant differences in nodule size were measured between TLC and RV scans. This has important implications for standardizing acquisition protocols in any setting where size and, more important, size change are being used for purposes of lung cancer staging, nodule characterization, or treatment response assessment.     

The effect of trial size on statistical power.

Many research studies produce results that falsely support a null hypothesis due to a lack of statistical power. The purpose of this research was to demonstrate selected relationships between single subject (SS) and group analyses and the importance of data reliability (trial size) on results. A computer model was developed and used in conjunction with Monte Carlo procedures to study the effects of sample size (subjects and trials), within- and between-subject variability, and subject performance strategies on selected statistical evaluation procedures. The inherent advantages of the approach are control and replication. Selected results are presented in this paper. Group analyses on subjects using similar performance strategies identified 10, 5, and 3 trials for sample sizes of 5, 10, and 20, respectively, as necessary to achieve statistical power values greater than 90% for effect sizes equal to one standard deviation of the condition distribution. SS analyses produced results exhibiting considerably less power than the group results for corresponding trial sizes, indicating how much more difficult it is to detect significant differences using a SS design. These results should be of concern to all investigators especially when interpreting nonsignificant findings.     

Combined radiofrequency ablation and adjuvant liposomal chemotherapy: effect of chemotherapeutic agent, nanoparticle size, and circulation time

PURPOSE: To evaluate the effects of liposomal chemotherapeutic agent, nanoparticle size, and liposome circulation time on tissue coagulation and intratumoral drug uptake when radiofrequency (RF) ablation is combined with adjuvant intravenous liposomal chemotherapy in an animal breast tumor model. MATERIALS AND METHODS: Ninety-one R3230 mammary adenocarcinoma nodules were implanted in 48 Fischer rats. First, standardized RF ablation was combined with intravenous liposomal doxorubicin, cisplatin, or 5-fluorouracil (35 tumors each). Second, three different-sized doxorubicin-containing nanoparticle preparations were combined with standardized RF ablation. Last, two doxorubicin-containing liposome preparations with different blood elimination half-lives were combined with RF ablation. Coagulation diameter and interstitial doxorubicin concentration were measured 48 hours after treatment and compared with use of statistical analysis. RESULTS: All combinations of RF with liposomal chemotherapy caused significantly greater tumor necrosis than RF alone (P<.05). Significantly increased necrosis was observed with intravenous liposomal RF/doxorubicin and RF/cisplatin compared with intravenous liposomal RF/5-fluorouracil (P<.01). Greater coagulation was observed with RF combined with 100-nm nanoparticles compared with 20-nm or 250-nm nanoparticles (P=.01 and P=.04, respectively). Additionally, greater intratumoral doxorubicin uptake was observed in the group treated with 20-nm nanoparticles compared with those treated with other sizes of nanoparticles (P<.05). RF plus liposomal doxorubicin produced greater coagulation and intratumoral doxorubicin uptake than RF plus 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid (P<.05). CONCLUSION: When combined with RF ablation, modification of adjuvant intravenous liposomal chemotherapy, including nanoparticle size, circulation time, and chemotherapeutic agent, can influence intratumoral drug accumulation and tissue coagulation.