Generation of ozone during irradiation using medical linear accelerators: an experimental study.

BACKGROUND: Some patients have noted a foul odor during radiation therapy sessions, but the cause of the odor remains unknown. Since we suspected that this phenomenon is due to ozone generated by ionizing radiation, this experimental study measured ozone concentrations in the treatment room and in a coiled polyvinyl chloride (PVC) tube placed within the radiation field. METHODS: We measured ozone concentrations using an ultraviolet absorption method and an ozone monitor. A PVC tube (inner diameter 7 mm, outer diameter 10 mm) was used to mimic the environment of the nasal cavity. The tube (790 cm) was coiled and set between two 4-cm-thick (for X-rays) or 2-cm-thick (for electron beams) water-equivalent solid phantoms. The sampling tube of the ozone monitor was inserted into the PVC tube, and the joint was sealed to prevent environmental air contamination. To measure ozone concentrations in the atmosphere, the sampling tube supplied with the unit was used. A linac was used on a full-sized treatment field (40 cm × 40 cm at a source-to-axis distance of 100 cm). The effect of an electron beam on ozone concentrations was also evaluated with a full-sized treatment field (40 cm × 40 cm at a source-to-surface distance of 100 cm). RESULTS: Ozone levels in the treatment room were undetectable before the start of daily treatment but reached 0.008 parts per million (ppm) or more at 1 h after the start of treatment. Concentrations then remained nearly constant at 0.010-0.015 ppm throughout the day. The maximum ozone concentration in the PVC tube was only 0.006 ppm, even when it was irradiated at 2400 monitor units/min. Depending on the X-ray dose rate, the concentration increased to a maximum of 0.010 ppm with oxygen flowing into the other end of the tube at 1.5 L/min. Ozone concentrations in the PVC tube did not differ significantly between X-ray and electron-beam irradiation. CONCLUSIONS: Only traces of ozone were found in the PVC tube that was used to mimic the nasal passages during radiation, these concentrations were too low for human perception. However, ozone concentrations did reach potentially detectable levels in the treatment room.

Therapeutic Effect of Sirolimus for Lymphangioleiomyomatosis Remaining in the Abdominopelvic Region After Lung Transplantation: A Case Report.

PURPOSE: Sirolimus (SRL) is used to treat pulmonary lymphangioleiomyomatosis (P-LAM). There is limited evidence that SRL has systemic efficacy for the patients with extrapulmonary lymphangioleiomyomatosis (E-LAM) remaining after lung transplantation (LT) for P-LAM. This report examines the efficacy of SRL treatment for the patient with E-LAM remaining after an LT for P-LAM. CASE SUMMARY: The course of the patient's recovery from an LT for P-LAM was complicated by lymphedema in the left femoral region that was caused by two E-LAM lesions remaining in the left pelvic cavity and in the retroperitoneal area. After the LT was performed, the patient started SRL treatment to reduce the E-LAM lesions. The daily SRL dose, selected based on the standard SRL dose for P-LAM, was initiated at 1 mg/d and was maintained at 2 mg/d. The remaining E-LAM lesions and lymphedema in the left femoral region improved in approximately 9 months after the LT with the administration of both SRL and the standard immunosuppressive therapy used by Okayama University Hospital, including tacrolimus, mycophenolate mofetil, and prednisolone. The SRL and tacrolimus trough concentrations in whole blood were maintained within the therapeutic window for the next 1.5 years after initiation of SRL treatment. The patient experienced no severe adverse events that required discontinuation of the SRL treatment during this time. CONCLUSION: The patients with remaining E-LAM lesions may receive SRL treatment to improve the quality of life after LT for P-LAM as effective therapy in cases where the patient's recovery is complicated by E-LAM lesions.

Design study of electron cyclotron resonance-ion plasma accelerator for heavy ion cancer therapy.

Electron Cyclotron Resonance-Ion Plasma Accelerator (ECR-IPAC) device, which theoretically can accelerate multiple charged ions to several hundred MeV with short acceleration length, has been proposed. The acceleration mechanism is based on the combination of two physical principles, plasma electron ion adiabatic ejection (PLEIADE) and Gyromagnetic Autoresonance (GYRAC). In this study, we have designed the proof of principle machine ECR-IPAC device and simulated the electromagnetic field distribution generating in the resonance cavity. ECR-IPAC device consisted of three parts, ECR ion source section, GYRAC section, and PLEIADE section. ECR ion source section and PLEIADE section were designed using several multi-turn solenoid coils and sextupole magnets, and GYRAC section was designed using 10 turns coil. The structure of ECR-IPAC device was the cylindrical shape, and the total length was 1024 mm and the maximum diameter was 580 mm. The magnetic field distribution, which maintains the stable acceleration of plasma, was generated on the acceleration center axis throughout three sections. In addition, the electric field for efficient acceleration of electrons was generated in the resonance cavity by supplying microwave of 2.45 GHz.

SU-E-T-142: Evaluation of the Energy Dependence of Gafchromic EBT3 Film for Electron Beams.

PURPOSE: To evaluate the energy dependence of Gafchromic EBT3 film for establishing a quality assurance method of bolus electron conformal radiotherapy. METHODS: We irradiated electron beam to EBT3 films, which were set in the water tank. The linear accelerator used was Varian Clinac 21EX. The energy of electron beams were 9 and 12 MeV. The irradiated field size was 10×10 cm2 and the source to surface distance was 100 cm. The depths of measurement were 22 (depth of dose maximum; dmax), 31, and 37 mm for 9 MeV and 28 (dmax), 43, and 50 mm for 12 MeV. The irradiated doses were 25, 50, 75, 100, 150, 200, and 300 cGy. EBT3 films were readout with a flat-bed scanner 48 hours after irradiation, and the optical density (OD) curve was obtained for each beam energy and depth. The OD curves were approximated by a third-order polynomial. The doses were evaluated at netOD 0.1 and 0.3 from the approximated curves. RESULTS: The differences of the evaluated doses from those for 9 MeV at 22 mm depth were from 2 to 14 % for netOD=0.1, and from 1 to 13 % for netOD=0.3, respectively. The netOD curves of dmax for both energies showed good agreement, while large discrepancy was found in the deeper depths. CONCLUSIONS: The dependence of dose response of EBT3 film on electron beam energy was small at dmax, while it increased at deeper depth in the present study. It can be considered that the discrepancy was caused by setup error because dose gradient was steeper at the deeper region. In future work, we will perform more precise measurement with a solid phantom to evaluate the energy dependence of EBT3 film.

SU-E-T-497: Study of Restricted Mass Stopping Power Ratio in Small Electron Tube Fields.

PURPOSE: Electron tubes with small radii are useful to treat narrow regions which cannot accommodate normal electron applicators. In small electron fields, it is not trivial to estimate restricted mass stopping power ratio (MSR), which is needed to evaluate dose from ion chamber measurement. We studied MSRs in small electron tube fields using the Monte Carlo simulation. METHODS: Electron tubes with radii, 3 and 2.5 cm, were used in this study. Nominal electron energies were 6 and 9 MeV. There were two types of tubes. One has a normal cut but the other has a 45-degree cut. For the normal cut tube, percent depth dose (PDD) in water was evaluated along the center of axis (CAX) of a beam. For the 45-degree cut tube, PDD was evaluated along the vertical line from the intersection of the CAX and the phantom surface with 45-degree gantry angle. The MSRs and mean electron energies were calculated using the Monte Carlo simulation. RESULTS: We found good agreement between the measured and calculated PDDs. The changes of mean energies from those in the 10×10 cm2 field at the depth of maximum dose (dmax) were very small for the normal cut electron tubes. For the 45-degree cut tubes, the changes of mean energies at dmax were less than 1 MeV. The MSRs in the normal cut tube fields were almost the same as those in the 10×10 cm2 field at the corresponding depths. The MSRs for the 45-degree cut tubes deviated from those in the 10×10 cm2 by about 1% (1.5 % at most). CONCLUSIONS: We evaluated the mean energies and MSRs in small electron tube fields. The deviations of them from the values in the 10×10 cm2 were small. The maximum difference of MSR was 1.5% in 45-degree cut tube fields. This work was supported by KAKENHI (23791449), Japan Society for the Promotion of Science, and Cancer Professional Training Plan, The Ministry of Education, Culture, Sports, Science and Technology, Japan.

Transvaginal mesh (TVM) reconstruction with TVT/TOT sling for vaginal prolapse concurrent with stress urinary incontinence.

We evaluated clinical efficacies of transvaginal mesh (TVM) reconstruction alone and those concomitant with a TVT/TOT sling for the treatment of pelvic organ prolapse (POP) and stress urinary incontinence (SUI). Between January 2006 and February 2007, 138 female patients with POP underwent TVM reconstruction. The mean age was 66.6 years (range: 52-84). Fourteen individuals were qualified as grade II in the POP quantification (POP-Q) system, 85 and 39 were grades III and IV, respectively. One hundred and seventeen of 138 (85 %) cases showed SUI. Twenty-one patients without SUI underwent TVM alone, and 117 cases with SUI underwent TVM concomitant with TVT/TOT sling. Mean operation time and intra-operative bleeding was 79 min (range: 25-177) and 74 ml (range: 10-429), respectively. Mean follow-up period is 5.3 months (range: 1-14). The vaginal prolapses were cured (grade 0) in 129 cases (93 %) after the surgery. Total inter-national prostate symptom score (IPSS), its QOL score, International Consultation on Incontinence Questionnaires Short Form (ICIQ-SF) significantly improved (from 12.6 to 3.9; p < 0.0001, from 5.0 to 1.0; p < 0.0001, and from 6.1 to 2.5; p < 0.01, respectively). Six of 21 cases (29%) who underwent TVM alone showed postoperative de-novo SUI. In contrast, 116 cases (99%) who underwent TVM concomitant with TVT/TOT, experienced a cure of SUI. Maximum flow rate did not change postoperatively in the both groups. In conclusion, the short-term efficacies of TVM reconstruction for POP are excellent, and a concomitant TVT/TOT sling prevents postoperative SUI.

Costimulatory blockade-mediated lung allograft acceptance is abrogated by overexpression of Bcl-2 in the recipient.

Lung allografts are considered to be more immunogenic than other solid organs. Little is known about the effectiveness of immunosuppressive regimens after lung transplantation. Herein, we describe a novel model of murine vascularized orthotopic lung transplantation we used to study the effects of costimulatory blockade on lung rejection. Transplants were performed in the Balb --> B6 strain combination. Recipients were either not immunosuppressed or received perioperative CD40/CD40L and CD28/B7 costimulatory blockade. Nonimmunosupressed Balb/c --> B6 lung transplants had severe acute rejection 7 days after transplantation and CD8(+) T cells outnumbered CD4(+) T cells within the allografts. Alternatively, B6 recipients that received perioperative costimulatory blockade had minimal inflammation and there were nearly equal numbers of CD8(+) and CD4(+) T cells in these grafts. Approximately one third of graft-infiltrating CD4(+) T cells expressed Foxp3. CD4(+) T cells isolated from these grafts induced apoptosis of alloreactive CD8(+) T cells that were stimulated with donor splenocytes in vitro. In contrast with wild-type B6 recipient mice, we observed severe rejection of Balb/c lungs 7 days after transplantation into Bcl-2 transgenic B6 recipients that had received costimulatory blockade. CD8(+) T cells outnumbered CD4(+) T cells in these immunosuppressed Bcl-2 transgenic recipients and, compared with immunosuppressed wild-type B6 recipients, a lower percentage of graft-infiltrating CD4(+) T cells expressed Foxp3, and a higher percentage of graft-infiltrating CD8(+) T cells expressed intereferon-gamma. Thus, our results show that perioperative blockade of the CD40/CD40L and CD28/B7 costimulatory pathways markedly ameliorates acute rejection of lung allografts in wild type but not Bcl-2 transgenic recipients.

Monocyte differentiation is controlled by MyD88 after mouse orthotopic lung transplantation.

In lung grafts, ischemia-reperfusion signals rapidly induce the recruitment and differentiation of host monocytes into macrophages and dendritic cells. The nature of ischemia-reperfusion signals are antigen independent, but have been hypothesized to initiate Toll-like receptor (TLR) and interleukin (IL)-1R-mediated signaling pathways that are thought to potentiate alloimmune responses. We wondered whether MyD88, an adaptor molecule critical for both TLR and IL-1R-mediated inflammatory responses, regulated monocyte differentiation in a mouse model of vascularized orthotopic lung transplantation. Orthotopic left lung transplants were performed in the following syngeneic combinations: CD45.1(+) B6 --> CD45.2(+) MyD88(-/-) and CD45.1(+) B6 --> CD45.2(+) B6. One day later, recipient-derived dendritic cells and macrophage numbers were assessed in the bronchiolar lavage by FACS analysis. Compared with the bronchiolar lavage of wildtype recipients, MyD88(-/-) recipients had lower numbers of dendritic cells in lung graft airways that were of recipient origin. Lower numbers of newly differentiated lung graft dendritic cells was coincident with the appearance of higher numbers of undifferentiated monocytes in the lung airways of MyD88(-/-) recipients as compared with wild-type recipients. Moreover, adoptive transfer experiments demonstrated that MyD88(-/-) monocytes were poorer at differentiating into lung dendritic cells as compared with wild-type monocytes. Taken together, these data show that MyD88 regulates graft-infiltrating monocyte differentiation and suggests a mechanism by which TLR/IL-1R-signaling pathways control adaptive responses in lung allografts through controlling monocyte fate.

Serum stem cell growth factor for monitoring hematopoietic recovery following stem cell transplantation.

Stem cell growth factor (SCGF) is a novel cytokine for primitive hematopoietic progenitor cells. Although it has burst-promoting activity and granulocyte/macrophage colony-promoting activity in vitro, its significance in hematopoiesis in vivo has not been elucidated. In this study, we have established enzyme-linked immunosorbent assay (ELISA) to quantify human SCGF and measured serum cytokines in normal volunteers and 27 patients undergoing stem cell transplantation (SCT), including six autologous and 21 allogeneic transplants. SCGF levels gradually increased after SCT regardless of graft-versus-host disease or type of transplant. The maximum level of SCGF was observed during the rapid granulocyte recovery phase in patients subjected to an autologous transplantation, and during the granulocyte stabilization phase in allogeneic patients. SCGF levels in PBSCT patients began to rise earlier than in BMT patients. Two patients with no increment of SCGF after SCT showed delayed engraftment. The source of SCGF was further analyzed by RT-PCR and we found that SCGF was highly expressed in bone marrow (BM) CD34(+) and CD34(-)CD33(+) cells, but not in BM CD34(-)CD33(-) cells, BM stromal cells and peripheral blood cells. The cell population expressing SCGF in BM possess the colony-forming cell activity. Therefore, serum SCGF can be an indicator of hematopoietic recovery following SCT.

[Treatment of strategy for traumatic disruption of the thoracic aorta accompanied by multiple trauma].

Disruption of the thoracic aorta due to blunt chest trauma is often fatal and should generally be treated surgically as soon as possible. However, cases of disruption of the thoracic aorta due to blunt chest trauma are often complicated by damage to vital organs, making treatment difficult. Our policy is to treat other organs before treating the thoracic aorta in 1) cases in which fracture of the pelvic bone or bleeding from abdominal cavity organs is causing shock and 2) cases of severe cerebral contusion or intracranial hemorrhage that require emergency surgical treatment. The use of a stent for treatment of acute-stage cases should be considered prudently.

[Perioperative management of patient with pulmonary operation associated with interstitial pneumonia].

The prognosis of patients complicated with interstitial pneumonia (IP) who undergo pulmonary operations is very poor if acute exacerbation occurs after the operation. We have experienced 6 cases in which operations were performed on lungs complicated with IP The first patient died due to acute exacerbation, but the subsequent 5 patients had good postoperative courses due to 1) short-term administration of low-dose steroid before and after the operation, 2) avoidance of administration of high concentration of oxygen during and after the operation, and 3) administration of erythromycin before and after the operation, 4) N-acetylcysteine inhalation and administration of dl-alpha-tocopherylnicotinate before and after the operation. It is thought that careful management of such patients is needed to prevent acute exacerbation even after discharge from hospital.

DNA cytofluorometric analysis of chondrocytes in human articular cartilages under normal aging or arthritic conditions.

OBJECTIVE: Since most chondrocytes in articular cartilage are in the resting phase (G0) of the cell cycle, it has been difficult to investigate their cell kinetics using 3H-thymidine autoradiography, or immunohistochemistry. In the present study, DNA cytofluorometry, which is useful to analyse the cell kinetics even for such inactive cell populations as in the G0 phase, was applied to human chondrocytes of the articular cartilages under normal aging and pathologic conditions such as osteoarthritis (OA), rheumatoid arthritis (RA), and aseptic necrosis (AN). DESIGN: The human articular cartilages for the study were obtained from autopsy and surgical materials. Fifty joints were used for the study of aging, 54 for the study of OA, 20 for studying RA, and 10 for AN study. The isolated chondrocytes were quickly prepared from fresh articular cartilages, using a combination method of enzymatic digestion with papain and collagenase, followed by mechanical cell separation by churning and homogenization. RESULTS: The DNA histograms obtained by cytofluorometry with propidium-iodide staining showed that most chondrocytes had diploid DNA content (2c) in all cartilages studied, suggesting that they were in the G0 phase. However, there were a few chondrocytes having tetraploid DNA content (4c) in the normally aged articular cartilages, and there were some cells having DNA content between 2c and 4c in the diseased cartilages. The former cells were considered to be G0-phase cells of the 4c chondrocytes, while the latter cells were considered to be in the DNA synthetic (S) phase or G2-phase of the 2c chondrocytes. The frequency of 4c chondrocytes in aged cartilage was significantly increased, compared to that in the young cartilage. In contrast to the normal cartilage, the frequency of S- and G2-phase cells, which was expressed as the S- G2 index, in diseased cartilages (OA, RA and AN) was significantly high (P< 0.0001). In OA cartilage, the S-G2 index was much higher in the severe or moderate stage than in the mild stage, suggesting that the chondrocytes in clusters may actively proliferate. CONCLUSION: These results showed that in normal articular cartilages most chondrocytes are in the G0 phase, while some became 4c polyploid cells, and that these G0-phase chondrocytes had a potential to proliferate under diseased conditions.

Aneurysmal change in an internal mammary artery-pulmonary artery fistula.

We treated a rare case of aneurysm of the internal mammary artery-pulmonary artery fistula in a 32-year-old woman with unrepaired pulmonary atresia and ventricular septal defect. This aneurysm communicated with the pulmonary artery system through an aortopulmonary collateral. Aneurysmectomy was successful.

Glucagon-like peptide isolated from the eel intestine: effects on atrial beating.

A new glucagon-like peptide was isolated from the intestine of the eel Anguilla japonica. The primary structure was determined by sequence analysis after cleavage with lysyl endopeptidase, quantitative amino acid analysis and fast atom bombardment mass spectrometry as HSQGTFTNDY(10)SKYLETRRAQ(20)DFVQWLMNSK(30)RSGGPT. Since its structure is similar to that of oxyntomodulins (OXMs) reported in various vertebrates, we named this peptide eel oxyntomodulin (eOXM). We found that eOXM enhanced the contractile force and the beating rate of the eel atrium in a dose-dependent manner. These effects of eOXM were not inhibited by betaxolol, a beta(1)-adrenoceptor antagonist, indicating that the actions of eOXM were independent of those of adrenaline. eOXM enhanced the intracellular Ca(2+) concentration of the myocardium. The contractility of the eel atrium was greatly reduced after omitting Ca(2+) from the bathing medium or after treatment with verapamil, a Ca(2+) channel blocker. After inhibiting Ca(2+) entry under these conditions, the inotropic effect of eOXM was markedly reduced, but the chronotropic effect was not altered significantly. These results indicate that the inotropic effect of eOXM is via a stimulation of Ca(2+) influx but that the chronotropic effect may be independent of extracellular Ca(2+).

A reoperation for anomalous origin of right pulmonary artery: report of a case.

A reoperation to upsize the conduit placed at infancy for the repair of an anomalous origin of the right pulmonary artery (AORPA) was successfully performed in an 8-year-old girl because of an elevated right ventricular pressure and a reduced right pulmonary blood flow. Although primary direct anastomosis is essential for AORPA, one should not hesitate to perform a conduit repair (interposition with a tube prosthesis) on an infant with AORPA whose right pulmonary artery is distant from the main pulmonary artery, because a reoperation can safely be performed even in cases where the conduit is relatively narrow as the patient grows. This is the first report of a reoperation, including a complete replacement of the conduit, after an initial conduit repair for AORPA.

Histopathologic analysis of angiogenic factors in localized renal cell carcinoma: the influence of neoadjuvant treatment.

BACKGROUND: This study was conducted in order to clarify whether histopathologic analysis of factor thymidine phosphorylase (TP) and Factor VIII could be a useful predictor of postoperative recurrence in localized renal cell carcinoma. Therefore, the relationship between tumor infiltrated lymphocytes (TIL) and both TP and Factor VIII was studied. METHOD: Of the 71 patients who underwent surgery, 54 patients had no neoadjuvant therapy (group 1), 10 patients were preoperatively administered IFN-gamma (group 2), and the remaining seven patients preoperatively received IFN-gamma and transarterial embolization (group 3). Both TP and Factor VIII immunostaining were performed on formalin-fixed, paraffin-embedded archival tissue from 71 renal cell carcinoma specimens, while TIL immunostaining was performed on frozen sections. Positive immunostaining was quantitatively scored by a computer-assisted digital image analysis. For TIL, positive results were semiquantitatively scored. RESULTS: A significant difference in the recurrence-free rate was recognized for Groups 1, 2 and 3 (P < 0.05). Therefore, the median TP-positive rate (PR), VIII-PR, number of microvessels and positive mean vascular area levels were investigated, between the recurrence cases (n = 6) and the recurrence-free cases (n = 11). Only the TP-PR levels showed a significant difference among them (P = 0.044). In regards to the neoadjuvant cases, a significant correlation was observed between both VIII-PR and CD4 (r = 0.815) as well as between VIII-PR and CD11b (r = 0.756). CONCLUSION: There was no clear evidence that the neoadjuvant treatment would increase the recurrence-free survival in patients with localized renal cell carcinoma. TP-PR might be a predictor of postoperative recurrence in patients with localized renal cell carcinoma.

Stem cell growth factor: in situ hybridization analysis on the gene expression, molecular characterization and in vitro proliferative activity of a recombinant preparation on primitive hematopoietic progenitor cells.

INTRODUCTION: In situ hybridization of whole mouse fetuses and their tibias with a stem cell growth factor (SCGF) antisense probe demonstrated specific expression of SCGF mRNA around skeletal tissues, particularly in bone marrow cells, proliferating chondrocytes, the perichondrium and periosteum, but little expression in resting or hypertrophic chondrocytes. METHODS: Recombinant human (rh) SCGF-alpha was purified from a conditioned medium of SCGF-alpha gene-transfected CHO cells. The molecular mass of rhSCGF-alpha, 45 kDa, was shifted down to 40 kDa by digestion with endo-O-glycosidase and sialidase, suggesting O-glycosylation of rhSCGF-alpha with sialic acids. RESULTS: For human bone marrow CD34+Lin- cells, rhSCGF-alpha alone did not stimulate colony-formation, but small cluster-formation (10.3 +/- 2.5/1 x 10(3) CD34+Lin- cells). It promoted growth of erythroid and granulocyte/macrophage (GM) colonies in the primary culture with erythropoietin and GM colony-stimulating factor (CSF) or G-CSF, respectively, and further supported GM progenitor cells in a short-term liquid culture. In contrast, rhSCGF-alpha suppressed stem cell factor (SCF)-stimulated erythroid bursts, indicating some competitive interaction between SCGF and SCF. rhSCGF-alpha was synergistic with interleukin-3 and the flt3 ligand to enhance GM colony-growth, but not synergistic with those inducing ex vivo expansion of GM progenitor cells. CONCLUSION: SCGF is selectively produced by osseous and hematopoietic stromal cells, and can mediate their proliferative activity on primitive hematopoietic progenitor cells.