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Sample records for acute radiation pneumonitis

  1. Radiation pneumonitis

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    Amla, T.R.; Chakravarti, R.N.; Lal, K.

    1975-07-01

    Adult healthy rhesus monkeys were exposed to a course of roentgen irradiation over the chest and back to produce pulmonary changes simulating human radiation pneumonitis. Macroscopic and morphologic changes included dense adhesions, pleural thickening and increased consistency of the lungs. Microscopically the early reaction was characterized by dilatation of pulmonary vessels, microhaemorrhages, collapse of alveoli, permeation of the interstitial tissue with a fibrinous fluid and cells. In the late stage the fibrinous interstitial matrix was replaced by hyaline eosinophilic mass, fragmentation and dissolution of the elastic tissue and thickening of the alveolar walls. The cell population in the interstitial tissue showed decline and at places radiolytic effect. There was peribronchial and perivascular fibrosis and hyalinization and pulmonary arteries revealed marked degree of arteriosclerosis. The present study opens a new field for experimental research on the development of pulmonary hypertension as a post-irradiation complication.

  2. Corticosteroid refractory radiation pneumonitis that remarkably responded to cyclosporin A

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    Muraoka, Tomie; Bandoh, Shuji; Fujita, Jiro; Horiike, Atsushi; Ishii, Tomoya; Tojo, Yasunori; Kubo, Akihito; Ishida, Toshihiko [Kagawa Medical Univ., Miki (Japan)

    2002-09-01

    Radiation therapy is commonly used for the treatment of lung cancer. However, radiation pneumonitis frequently occurs as a complication of the radiation therapy. Although corticosteroids are widely used for the treatment of radiation pneumonitis, they are not always effective. In this report, we used cycosporin A in the treatment of a patient suffering from steroid-refractory radiation pneumonitis. To our knowledge, this is the first report in which cyclosporin A was successfully used in the treatment of radiation pneumonitis. (author)

  3. Migratory organizing pneumonitis `primed` by radiation therapy

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    Bayle, J.Y.; Nesme, P.; Guerin, J.C. [Hopital de la Croix Rousse, Service de Pneumologie, Lyon (France); Bejui-Thivolet, F. [Hopital de la Croix Rousse, Laboratorie d`Anatomopatologie, Lyon (France); Loire, R. [Hopital Cardiovasculaire et Pneumologique, Universite Claude Bernard, Laboratoire d`Anatomopathologie, Lyon (France); Cordier, J.F. [Hopital Cardiovasculaire et Pneumologique, Universite Claude Bernard, Service de Pneumologie, Lyon (France)

    1995-02-01

    We report on two women presenting with cough and fever, 4 and 7 months, respectively, after starting breast radiation therapy following surgery for breast carcinoma. Chest roentgenogram and computed tomographic (CT) scan demonstrated alveolar opacities, initially limited to the pulmonary area next to the irradiated breast, but later migrating within both lungs. Intra-alveolar granulation tissue was found in transbronchial lung biopsies. Corticosteroid treatment resulted in dramatic clinical improvment, together with complete clearing of the pulmonary opacities on chest imaging. However, clinical and imaging relapses occurred when corticosteroids were withdrawn too rapidly; with further improvment when they were reintroduced. The reported cases clearly differ from radiation pneumonitis. They were fairly typical of cryptogenic organizing pneumonitis, also called idiopathic bronchiolitis obliterans organizing pneumonia, with the exception of the radiation therapy, partially affecting the lung, which had been performed within the previous months. Since focal radiation therapy involving the lung may induce diffuse bilateral lymphocytic alveolitis, we hypothesize that this may `prime` the lung to further injury, leading to cryptogenic organizing pneumonitis. (au) (26 refs.).

  4. Radiation recall pneumonitis induced by gemcitabine

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    Schwarte, S.; Karstens, J.H.; Bremer, M. [Medical School Hannover (Germany). Dept. of Radiation Oncology; Wagner, K. [Medical School Hannover (Germany). Dept. of Hematology, Hemastaseology and Oncology

    2007-04-15

    Background: Radiation recall pneumonitis describes a very rare reaction in a previously irradiated area of pulmonary tissue after application of pharmacological agents. A case of recall pneumonitis induced by gemcitabine is reported. Case Report: A 64-year-old female patient with metastasized esophageal carcinoma received simultaneous chemoradiotherapy of the upper mediastinum with 50.4 Gy and cisplatin/5-fluorouracil. 8 months later she was scheduled for salvage chemotherapy with gemcitabine (1,000 mg/m2 days 1 and 8) and docetaxel (75 mg/m2 day 8) due to locally progressive disease. After having received gemcitabine on day 1 of the second course, the patient developed dry cough, subfebrile temperatures and dyspnea within 48 h. A CT of the thorax revealed newly developed bilateral pulmonary ground-glass opacity corresponding to the previous radiation fields. Chemotherapy was stopped and systemic application of prednisolone was initiated. 2 months later symptoms had resolved with a control CT of the thorax showing complete regression of the pulmonary changes. Conclusion: Gemcitabine-induced recall pneumonitis is a rarely reported phenomenon and should be taken into account even after extended time interval to the previous radiotherapy.

  5. Acute chemical pneumonitis caused by nitric acid inhalation: case report

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    Choe, Hyung Shim; Lee, In Jae; Ko, Eun Young; Lee, Jae Young; Kim, Hyun Beom; Hwang, Dae Hyun; Lee, Kwan Seop; Lee, Yul; Bae, Sang Hoon [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2003-06-01

    Chemical pneumonitis induced by nitric acid inhalation is a rare clinical condition. The previously reported radiologic findings of this disease include acute permeability pulmonary edema, delayed bronchiolitis obliterans, and bronchiectasis. In very few published rare radiologic reports has this disease manifested as acute alveolar injury; we report a case of acute chemical pneumonitis induced by nitric acid inhalation which at radiography manifested as bilateral perihilar consolidation and ground-glass attenuation, suggesting acute alveolar injury.

  6. Incidence and Prognostic Factors of Radiation Pneumonitis

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    Kim, M. S. [Yeungnam University College of Medicine, Daegu (Korea, Republic of)

    2008-03-15

    To evaluate the incidence and prognostic factors of treatment-related pneumonitis in non-small-cell lung cancer (NSCLC) patients treated with intensity modulated radiation therapy (IMRT). One-hundred-five patients with NSCLC treated with IMRT between 1 August 2004 and 30 November 2006 were analyzed retrospectively. The mean age of patients was 62.9 years, and squamous carcinomas were confirmed in 81 patients (77%). Sixty-six patients (62.9%) were classified as stage III, and 59 patients had lesions in the right lung. Twenty-seven patients were treated with a dose of 3,060 cGy preoperatively, and 10 patients were given a dose of 5,040 cGy postoperatively. Sixty-eight patients received a dose of 7,020 cGy for curative intent. Sixty-eight patients were treated with the use of the CORVUS planning system and 37 patients were treated with the use of the ECLIPSE planning system. Of 105 patients, 21 patients (20%) had abnormal radiological findings, but only seven patients (6.7%) required treatment for radiation pneumonitis. Six of the seven patients had other serious lesions, including a bronchioesophageal fistula (one patient), recurrence in the treatment field (two patients), brain metastasis (one patient) and lung-to-lung metastasis (two patients); all of these patients died within 19 months after radiation treatment. Sixteen patients (23.5%) that received planning with the CORVUS system had abnormal lung findings. Five patients (13.5%) had abnormal lung findings with the use of the ECLIPSE planning system. Other prognostic factors such as perioperative radiation therapy, a volume over 10% of the V20 volume in the right lung, were also statistically significant. This retrospective analysis suggests that IMRT could be a beneficial treatment modality for the reduction of radiation pneumonitis in NSCLC patients. However, the higher incidence of abnormal radiological findings in perioperative patients treated with relatively lower doses (3,060{approx}5,040 cGy) suggest the

  7. Chlorambucil-Induced Acute Interstitial Pneumonitis

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    Hammad Shafqat

    2014-01-01

    Full Text Available Chlorambucil is an alkylating agent commonly used in treatment of chronic lymphocytic leukemia (CLL. We report a case of interstitial pneumonitis developing in an 83-year-old man 1.5 months after completing a six-month course of chlorambucil for CLL. The interstitial pneumonitis responded to therapy with prednisone. We performed a systematic review of literature and identified 13 other case reports of chlorambucil-induced pulmonary toxicity, particularly interstitial pneumonitis. No unifying risk factor could be discerned and the mechanism of injury remains unknown. In contrast, major randomized trials of chlorambucil therapy in CLL have not reported interstitial pneumonitis as an adverse effect, which may be due to the rarity of the phenomenon or due to underreporting of events occurring after completion of treatment. Clinicians should consider drug-induced interstitial pneumonitis in the differential diagnosis of a suggestive syndrome developing even after discontinuation of chlorambucil.

  8. Acute pneumonitis secondary to subcutaneous silicone injection

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    Gopie P

    2011-06-01

    Full Text Available Priya Gopie, Sateesh Sakhamuri, Anu Sharma, Sanjeev Solomon, Surujpal TeelucksinghClinical Medical Sciences, University of the West Indies, St Augustine, TrinidadAbstract: Following silicone injection, end organ toxicity can occur. To our knowledge this report documents the first case of silicone embolization in the Caribbean and serves to highlight an emergent danger associated with its illicit use for cosmetic purposes in this region.Keywords: silicone, silicone embolism, silicone pneumonitis, alveolar hemorrhage, pneumonitis

  9. Experimental treatment of radiation pneumonitis with human umbilical cord mesenchymal stem cells

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    Rui Wang; Chang-zheng Zhu; Ping Qiao; Jian Liu; Qiang Zhao; Kui-jie Wang; Ting-bao Zhao

    2014-01-01

    Objective: To evaluate of the curative effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on rat acute radiation pneumonitis. Methods: Fourty rats were randomly divided into control group, radiation group, stem cell prevention group, stem cell treatment group and prednisone treatment group. All rats except those in the control group were radiated with X ray to establish the acute radiation pneumonitis damage model. The hUC-MSCs cultured in vitro was administrated to the rats of the prevention group via tail vein (1×106 cells/kg BW) 24 h before the radiation, while the same administration was performed in the rats of the treatment group 24 h after the radiation. After 24 h post the radiation, the rats in the radiation group were given 0.4 mL physiological saline, and those in the prednisone group were given 1 mg/kg prednisone. All rats were observed and executed 72 h after the radiation to detect lung histological changes. Results:After the administration of hUC-MSCs, the survival status of the rats in the prevention group and treatment group was obviously better than that in the control group. As shown by the histological staining, the morphology, proliferation activity and bronchial state of lung tissues were better in the prevention group and treatment group than in the control group. Conclusion: The hUC-MSCs have definite therapeutic effects on acute radiation pneumonitis in rats.

  10. Hypofractionation does not increase radiation pneumonitis risk with modern conformal radiation delivery techniques

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    Vogelius, Ivan R; Westerly, David C; Cannon, George M

    2010-01-01

    To study the interaction between radiation dose distribution and hypofractionated radiotherapy with respect to the risk of radiation pneumonitis (RP) estimated from normal tissue complication probability (NTCP) models.......To study the interaction between radiation dose distribution and hypofractionated radiotherapy with respect to the risk of radiation pneumonitis (RP) estimated from normal tissue complication probability (NTCP) models....

  11. Radiation pneumonitis after stereotactic radiation therapy for lung cancer

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    Hideomi; Yamashita; Wataru; Takahashi; Akihiro; Haga; Keiichi; Nakagawa

    2014-01-01

    Stereotactic body radiation therapy(SBRT)has a locacontrol rate of 95%at 2 years for non-small cell lungcancer(NSCLC)and should improve the prognosis oinoperable patients,elderly patients,and patients withsignificant comorbidities who have early-stage NSCLCThe safety of SBRT is being confirmed in internationalmulti-institutional PhaseⅡtrials for peripheral lungcancer in both inoperable and operable patients,bureports so far have found that SBRT is a safe and effective treatment for early-stage NSCLC and early metastatic lung cancer.Radiation pneumonitis(RP)is oneof the most common toxicities of SBRT.Although mospost-treatment RP is Grade 1 or 2 and either asymptomatic or manageable,a few cases are severe,symptomatic,and there is a risk for mortality.The reportedrates of symptomatic RP after SBRT range from 9%to28%.Being able to predict the risk of RP after SBRT isextremely useful in treatment planning.A dose-effecrelationship has been demonstrated,but suggesteddose-volume factors like mean lung dose,lung V20and/or lung V2.5 differed among the reports.We foundthat patients who present with an interstitial pneumo-nitis shadow on computed tomography scan and high levels of serum Krebs von den Lungen-6 and surfactant protein D have a high rate of severe radiation pneumo-nitis after SBRT.At our institution,lung cancer patients with these risk factors have not received SBRT since 2006,and our rate of severe RP after SBRT has de-creased significantly since then.

  12. Radiation dermatitis and pneumonitis following breast conserving therapy

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    Yoden, Eisaku; Hiratsuka, Junichi; Imajo, Yoshinari [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    2000-09-01

    We investigated the frequency, degree and risk factors of radiation-induced dermatitis and pneumonitis in 255 patients receiving breast conserving therapy between April 1987 and April 1998. The majority of the patients underwent a wide excision or quadrantectomy with a level I, II axillary dissection, followed by radiotherapy consisting of 50 Gy/25 Fr/5 weeks to the preserved breast with a 4 MV beam by tangentially opposed portals using the half-field technique. Eleven patients received an additional 10 Gy/5 Fr of electron therapy to the tumor bed. Most of the patients developed radiation dermatitis which was limited to reddening or dry desquamation, with the exception of 14 patients with a localized moist reaction. The skin reaction was transient in all patients and improved with conservative treatments. Radiation pneumonitis appeared on chest X-rays in 30 patients, with a slight appearance in 21 and patchy appearance in 9. Three patients presented with persistent symptoms requiring medication. They were treated with steroids, resulting in complete resolution of the symptoms. A large volume of the chest wall within the irradiation field and a large area of irradiated skin were the risk factors of radiation dermatitis. The volume of irradiated lung significantly correlated with the frequency and degree of radiation pneumonitis. It was preferable that the maximum thickness of the involved lung should not exceed 3 cm. Complicated disease, adjuvant therapy and boost irradiation had no impact on the radiation dermatitis or pneumonitis. (author)

  13. Bilateral acute lupus pneumonitis in a case of rhupus syndrome

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    Supriya Sarkar

    2012-01-01

    Full Text Available Rhupus syndrome, the overlap of rheumatoid arthritis (RA and systemic lupus erythematosus (SLE, is an extremely uncommon condition. Organ damages found due to SLE are usually mild in rhupus. Lupus pneumonitis in rhupus syndrome has not been reported worldwide. We are reporting a 23-year-old female with bilateral symmetric erosive arthritis, oral ulcer, alopecia, polyserositis, anemia, leucopenia, positive RA-factor, anti nuclear antibody (ANA and anti ds-DNA. She presented with acute onset dyspnea, high fever, chest pain, tachycardia, tachypnea, hypoxia and respiratory alkalosis. High resolution computed tomography (HRCT-thorax showed bilateral, basal consolidation with air bronchogram. Repeated sputum and single broncho alveolar lavage (BAL fluid examination revealed no organism or Hemosiderin-laden macrophage. The diagnosis of rhupus was confirmed by combined manifestations of RA and SLE, and the diagnosis of acute lupus pneumonitis was established by clinico-radiological picture and by excluding other possibilities.

  14. Bilateral acute lupus pneumonitis in a case of rhupus syndrome.

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    Sarkar, Supriya; Saha, Kaushik

    2012-07-01

    Rhupus syndrome, the overlap of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), is an extremely uncommon condition. Organ damages found due to SLE are usually mild in rhupus. Lupus pneumonitis in rhupus syndrome has not been reported worldwide. We are reporting a 23-year-old female with bilateral symmetric erosive arthritis, oral ulcer, alopecia, polyserositis, anemia, leucopenia, positive RA-factor, anti nuclear antibody (ANA) and anti ds-DNA. She presented with acute onset dyspnea, high fever, chest pain, tachycardia, tachypnea, hypoxia and respiratory alkalosis. High resolution computed tomography (HRCT)-thorax showed bilateral, basal consolidation with air bronchogram. Repeated sputum and single broncho alveolar lavage (BAL) fluid examination revealed no organism or Hemosiderin-laden macrophage. The diagnosis of rhupus was confirmed by combined manifestations of RA and SLE, and the diagnosis of acute lupus pneumonitis was established by clinico-radiological picture and by excluding other possibilities.

  15. Imaging radiation pneumonitis in a rat model of a radiological terrorism incident

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    Molthen, Robert; Wu, QingPing; Krenz, Gary; Medhora, Meetha; Jacobs, Elizabeth; Moulder, John E.

    2009-02-01

    We have developed a rat model of single, sub-lethal thoracic irradiation. Our irradiation protocol is considered representative of exposures near the detonation site of a dirty bomb or small nuclear device. The model is being used to investigate techniques for identifying, triaging and treating possible victims. In addition to physiological markers of right ventricular hypertrophy, pulmonary vascular resistance, and arterial distensibility, we present two methods for quantifying microvascular density. We used methods including microfocal X-ray imaging to investigate changes in lung structure/function resulting from radiation exposure. Radiation pneumonitis is a complication in subjects receiving thoracic irradiation. A radiographic hallmark of acute radiation pneumonitis is a diffuse infiltrate corresponding to the radiation treatment field. We describe two methods for quantifying small artery dropout that occurs in the model at the same time-period. Rats were examined 3-days, 2-weeks, 1-month (m), 2-m, 5-m, and 12-m post-irradiation and compared with aged-matched controls. Right ventricular hypertrophy and increases in pulmonary vascular resistance were present during the pneumonitis phase. Vascular injury was dependent on dose and post-irradiation duration. Rats irradiated with 5 Gy had few detectable changes, whereas 10 Gy resulted in a significant decrease in both microvascular density and arterial distensibility around 2- m, the decrease in each lessening, but extending through 12-m. In conclusion, rats irradiated with a 10 Gy dose had changes in vascular structure concurrent with the onset of radiation pneumonitis that were detectable with our imaging techniques and these structural changes persist after resolution of the pneumonitis.

  16. Acute respiratory failure secondary to mesalamine-induced interstitial pneumonitis.

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    Abraham, Albin; Karakurum, Ali

    2013-08-20

    Interstitial pneumonitis as an adverse effect of mesalamine therapy is a rare but potentially serious complication. Patients typically have a mild disease course with no documented cases of respiratory failure in published literature. Given its variable latent period and non-specific signs and symptoms, it may be difficult to diagnose. We present the case of a 65-year-old man who presented with symptoms of fever, shortness of breath and a non-productive cough, 2 weeks after initiation of therapy with mesalamine. His hospital course was complicated by acute respiratory failure requiring intubation and mechanical ventilation. Radiographic studies revealed bilateral lower lobe infiltrates and bronchosopy with bronchoalveolar lavage and transbronchial biopsy were consistent with a diagnosis of drug-induced interstitial pneumonitis. The aim of this paper is to highlight the importance of considering a diagnosis of mesalamine-induced lung injury in patients presenting with respiratory symptoms while on mesalamine therapy and to review relevant literature.

  17. Protective effect of corticosteroids on radiation pneumonitis in mice

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    Gross, N.J.; Narine, K.R.; Wade, R.

    1988-01-01

    We explored the protective effect of corticosteroids on the mortality of mice that received thoracic irradiation. Methylprednisolone, 100 mg/kg/week, given from 11 weeks after gamma irradiation of the thorax resulted in an increase in the LD50 (11-26 weeks) from 14.3 +/- 0.3 (mean +/- SE) Gy to 17.6 +/- 0.4 Gy, P less than 0.001, a protection factor of 1.2. Withdrawal of steroids at various times during the period of radiation pneumonitis resulted in accelerated mortality in the next 2-4 weeks, so that the cumulative mortality caught up with that of control animals by 4 weeks after steroid withdrawal. However, after the end of the usual period of pneumonitis withdrawal of steroids did not result in accelerated mortality, suggesting that the time when steroids are protective corresponds to the duration of pneumonitis. A smaller dose of steroids, 25 mg/kg/week, was found to be as protective as the larger dose used in the above experiments. The possibility that corticosteroids reduce mortality, even when given many weeks after radiation, may have important practical and theoretical implications.

  18. Decreased Risk of Radiation Pneumonitis With Incidental Concurrent Use of Angiotensin-Converting Enzyme Inhibitors and Thoracic Radiation Therapy

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    Kharofa, Jordan [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Cohen, Eric P. [Department of Medicine, Division of Nephrology, Medical College of Wisconsin, Milwaukee, WI (United States); Tomic, Rade [Department of Medicine, Division of Pulmonology, Medical College of Wisconsin, Milwaukee, WI (United States); Xiang Qun [Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI (United States); Gore, Elizabeth, E-mail: Egore@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States)

    2012-09-01

    Purpose: Angiotensin-converting enzyme (ACE) inhibitors have been shown to mitigate radiation-induced lung injury in preclinical models. The aim of this study was to evaluate whether ACE inhibitors decrease the risk of radiation pneumonitis in lung cancer patients receiving thoracic irradiation. Methods and Materials: Patients with Stage I through III small-cell and non-small-cell lung cancer treated definitively with radiation from 2004-2009 at the Clement J. Zablocki Veterans Affairs Medical Center were retrospectively reviewed. Acute pulmonary toxicity was quantified within 6 months of completion of treatment according to the Common Terminology Criteria for Adverse Events version 4. The use of ACE inhibitors, nonsteroidal anti-inflammatory drugs, inhaled glucocorticosteroids, statins, and angiotensin receptor blockers; dose-volume histogram parameters; and patient factors were assessed for association with Grade 2 or higher pneumonitis. Results: A total of 162 patients met the criteria for inclusion. The majority of patients had Stage III disease (64%) and received concurrent chemotherapy (61%). Sixty-two patients were identified as ACE inhibitor users (38%). All patients had acceptable radiation plans based on dose-volume histogram constraints (V20 [volume of lung receiving at least 20 Gy] {<=}37% and mean lung dose {<=}20 Gy) with the exception of 2 patients who did not meet both criteria. Grade 2 or higher pulmonary toxicity occurred in 12 patients (7.4%). The rate of Grade 2 or higher pneumonitis was lower in ACE inhibitor users vs. nonusers (2% vs. 11%, p = 0.032). Rates of Grade 2 or higher pneumonitis were significantly increased in patients aged greater than 70 years (16% vs. 2%, p = 0.005) or in whom V5 (volume of lung receiving at least 5 Gy) was 50% or greater (13% vs. 4%, p = 0.04). V10 (volume of lung receiving at least 10 Gy), V20, V30 (volume of lung receiving at least 30 Gy), and mean lung dose were not independently associated with Grade 2 or

  19. A literature-based meta-analysis of clinical risk factors for development of radiation induced pneumonitis

    DEFF Research Database (Denmark)

    Vogelius, Ivan R; Bentzen, Søren M

    2012-01-01

    of symptomatic radiation pneumonitis (RP). Material and methods. A systematic review of English language articles in the Pubmed, Embase and Cochrane controlled trials registers. Studies with the mesh term "radiation pneumonitis" or the search term "radiation pneumonitis" were included. Additional studies were...

  20. [Effect of diabetes mellitus on the development of radiation pneumonitis in patients with non-small cell lung cancer].

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    Song, Hao; Yu, Jin-ming

    2009-01-01

    The purpose of this study was to investigate whether the associated diabetes mellitus exerts a certain effect on the development of radiation pneumonitis in patients with non-small cell lung cancer. 156 patients with non small cell lung cancer were treated with three-dimensional conformal radiation therapy in this study, including 52 associated with diabetes and 104 non-diabetic patients as a control group. All the patients were followed up for one year and the development of radiation pneumonitis was observed. Radiation pneumonitis was diagnosed according to the criteria of radiation therapy oncology group. The morbidities of radiation pneumonitis in the two groups were compared. The relationships between the morbidity of radiation pneumonitis and blood sugar level as well as diabetic history were analyzed by chi-square test. Twenty-one (40.4%) of 52 patients with diabetes had radiation pneumonitis (grade 2 or greater), while in the control group only 22 of 104 patients (21.2%) suffered from radiation pneumonitis. There was a statistically significant difference between the two groups in the morbidity of the radiation pneumonitis (P diabetic history was not significantly different from that in those with a shorter diabetic history (P > 0.05). Non-small cell lung cancer patients with diabetes mellitus are more vulnerable than those without to radiation pneumonitis. Therefore, diabetes mellitus is a newly discovered risk factor to radiation pneumonitis, and the blood sugar level is positively correlated with the morbidity of radiation pneumonitis.

  1. Analysis of radiation pneumonitis outside the radiation field in breast conserving therapy for early breast cancer

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    Ogo, Etsuyo; Fujimoto, Kiminori; Hayabuchi, Naofumi [Kurume Univ., Fukuoka (Japan). School of Medicine] (and others)

    2002-02-01

    In a retrospective study of radiation-induced pulmonary changes for patients with breast conserving therapy for early breast cancer, we sent questionnaires to the main hospitals in Japan. In this study, we analyzed pulmonary changes after tangential whole-breast irradiation. The purpose of this study was to determine the incidence and risk factors for radiation pneumonitis outside the radiation field. The questionnaires included patients data, therapy data, and lung injury information between August 1999 and May 2000. On the first questionnaires, answer letters were received from 107 institutions out of 158 (67.7%). On the second questionnaires, response rate (hospitals which had radiation pneumonitis outside the radiation field) was 21.7% (23/106). We could find no risk factors of this type of pneumonitis. We suggested that lung irradiation might trigger this type of pneumonitis which is clinically similar to BOOP (bronchiolitis obliterans organizing pneumonia). It developed in 1.5-2.1% among the patients with breast conserving surgery and tangential whole-breast irradiation. And it is likely appeared within 6 months after radiotherapy. (author)

  2. Steroid-withdrawal radiation pneumonitis in lung cancer patients with brain metastasis

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    Sugiyama, Akira; Katayama, Motoyuki; Ozeki, Yutaka [National Tohsei Hospital, Shizuoka (Japan)

    1995-07-01

    Of 13 patients with lung cancer who received corticosteroid administration for brain metastasis after lung irradiation, 5 developed steroid-withdrawal severe acute radiation pneumonitis. All patients were male, their age distribution was 48 to 80 years old (mean 63 years old). In all patients, the symptom developed shortly after the rapid withdrawal or reduction of corticosteroid. Clinical signs were characterized by fever, dyspnea and cough. Chest radiograph showed pulmonary infiltrate promptly in the radiation field and extending beyond the geometric beam boundary. CT scan was sensitive for the detection of early change of radiation injury. Compared with the control group, the irradiated volume of lung was bigger and the interval of irradiation and corticosteroid administration was shorter in onset group. When steroid is employed after or during the lung irradiation, the dosage must be tapered for long period to avoid this complication. (author).

  3. Heart irradiation as a risk factor for radiation pneumonitis

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    HUANG, ELLEN X.; HOPE, ANDREW J.; LINDSAY, PATRICIA E.; TROVO, MARCO; EL NAQA, ISSAM; DEASY, JOSEPH O.; BRADLEY, JEFFREY D.

    2013-01-01

    Purpose To investigate the potential role of incidental heart irradiation on the risk of radiation pneumonitis (RP) for patients receiving definitive radiation therapy for non-small-cell lung cancer (NSCLC). Material and methods Two hundred and nine patient datasets were available for this study. Heart and lung dose-volume parameters were extracted for modeling, based on Monte Carlo-based heterogeneity corrected dose distributions. Clinical variables tested included age, gender, chemotherapy, pre-treatment weight-loss, performance status, and smoking history. The risk of RP was modeled using logistic regression. Results The most significant univariate variables were heart related, such as heart heart V65 (percent volume receiving at least 65 Gy) (Spearman Rs = 0.245, p < 0.001). The best-performing logistic regression model included heart D10 (minimum dose to the hottest 10% of the heart), lung D35, and maximum lung dose (Spearman Rs = 0.268, p < 0.0001). When classified by predicted risk, the RP incidence ratio between the most and least risky 1/3 of treatments was 4.8. The improvement in risk modeling using lung and heart variables was better than using lung variables alone. Conclusions These results suggest a previously unsuspected role of heart irradiation in many cases of RP. PMID:20874426

  4. Heart irradiation as a risk factor for radiation pneumonitis

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    Huang, Ellen X.; El Naqa, Issam; Deasy, Joseph O.; Bradley, Jeffrey D. (Dept. of Radiation Oncology, Mallinckrodt Inst. of Radiology, Washington Univ. School of Medicine, St. Louis, Missouri (United States)), e-mail: jdeasy@radonc.wustl.edu; Hope, Andrew J.; Lindsay, Patricia E. (Princess Margaret Hospital, Toronto, ON (Canada)); Trovo, Marco (National Cancer Inst., Aviano (Italy))

    2011-01-15

    Purpose. To investigate the potential role of incidental heart irradiation on the risk of radiation pneumonitis (RP) for patients receiving definitive radiation therapy for non-small-cell lung cancer (NSCLC). Material and methods. Two hundred and nine patient datasets were available for this study. Heart and lung dose-volume parameters were extracted for modeling, based on Monte Carlo-based heterogeneity corrected dose distributions. Clinical variables tested included age, gender, chemotherapy, pre-treatment weight-loss, performance status, and smoking history. The risk of RP was modeled using logistic regression. Results. The most significant univariate variables were heart related, such as heart heart V65 (percent volume receiving at least 65 Gy) (Spearman Rs = 0.245, p < 0.001). The best-performing logistic regression model included heart D10 (minimum dose to the hottest 10% of the heart), lung D35, and maximum lung dose (Spearman Rs 0.268, p < 0.0001). When classified by predicted risk, the RP incidence ratio between the most and least risky 1/3 of treatments was 4.8. The improvement in risk modeling using lung and heart variables was better than using lung variables alone. Conclusions. These results suggest a previously unsuspected role of heart irradiation in many cases of RP

  5. Bronchoangiographic changes on different stages of radiation pneumonitis

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    Petkov, D.; Todorov, J. (Meditsinska Akademiya, Sofia (Bulgaria). Nauchen Inst. po Rentgenologiya i Radiobiologiya)

    1981-01-01

    Selective bronchoangiograms were discussed in 21 patients at the age from 35 to 54, operated on for breast carcinoma and irradiated by telegamma-therapeutic device ''Rocus'' with three direct and two tangential fields of total focal dosage from 4500 to 5000 rad, realised for 7 - 9 weeks. The selective bronchial arteriography after Seldinger was carried out on the corresponding side at different time intervals after radiation completion, as follows; from 2 - 3 months - in 10 patients and for about 1 year - in 11 patients. In different periods of the radiograms taken enlargement of the main tree of the bronchial artery and its branches and development of a rich interstitial network in 9 patients in the hilus and in 4 in the subclavian area were established. In two of these cases were observed direct anastomoses between the branches of the bronchial and pulmonary arteries which are recognized from their characteristic course. In the hilus or parenchyma of three patients focal accumulation of pathological vessels was established, suggestive of metastases. The angiograms of patients in late periods after radiotherapy (1 year) are characterized with segment narrowing of the lumen of the bronchial artery and its branches, zigzag fold movement, relatively scarce interstitial angiographic image and slowing down of the passage of the contrast material. In two patients of that group using contrast filling of the intercostal arteries visualization of relapses in soft tissues was achieved. The bronchial angiography should be introduced in the complex treatment in the complex examination of the characteristics and evolution of radiation pneumonitis.

  6. Radiation pneumonitis caused by a migrated brachytherapy seed lodged in the lung.

    Science.gov (United States)

    Miura, Noriyoshi; Kusuhara, Yoshito; Numata, Kousaku; Shirato, Akitomi; Hashine, Katsuyoshi; Sumiyoshi, Yoshiteru; Kataoka, Masaaki; Takechi, Shinsuke

    2008-09-01

    We report a case of radiation pneumonitis caused by a migrated seed lodged in the lung after prostate brachytherapy. A 71-year-old man underwent transperineal interstitial permanent prostate brachytherapy for localized prostate cancer. On the day after brachytherapy, a routine postimplant chest X-ray revealed migration of one seed to the lower lobe of the left lung. After 1 month, pulmonary opacities were observed in the left lower lobe but not near the seed. He was diagnosed with bacterial pneumonia, and antibiotic therapy was commenced. Two months after brachytherapy, the patient's symptoms, laboratory data and pulmonary opacities improved; however, an abnormal shadow (consolidation) developed around the migrated seed. Lung consolidation disappeared almost completely 12 months after brachytherapy without any medical treatment. The abnormal shadow probably represented radiation pneumonitis. To the best of our knowledge, this is the first report of radiation pneumonitis caused by a migrated brachytherapy seed in the lung.

  7. [18F]2-fluoro-2-deoxyglucose positron emission tomography/computed tomography in predicting radiation pneumonitis

    Institute of Scientific and Technical Information of China (English)

    SONG Hao; YU Jin-ming; Feng-ming Kong; LU Jie; BAI Tong; MA Li; FU Zheng

    2009-01-01

    Background Prevention is presently the only available method to limit radiation-induced lung morbidity. A good predictor is the key point of prevention. This study aimed to investigate if [18F]2-fluoro-2-deoxyglucose (FDG) uptake changes in the lung after radiotherapy could be used as a new predictor for acute radiation pneumonitis (RP). Methods Forty-one patients with lung cancer underwent FDG positron emission tomography/computed tomography (FDG-PET/CT) imaging before and after radiotherapy. The mean standardized uptake value (SUV) was measured for the isodose regions of 0-9 Gy, 10-19 Gy, 20-29 Gy, 30-39 Gy, 40-49 Gy. The mean SUV of these regions after radiotherapy was compared with baseline. The mean SUV in patients who developed RP was also compared with that in those who did not. The statistical difference was determined by matched pair t test. The Radiation Therapy Oncology Group (RTOG)criteria were used for diagnosis and grading of RP.Results With a median follow-up of 12 months, 11 (26.8%) of the 41 patients developed grade 2 and above acute RP.The mean SUV of regions (10-19 Gy, 20-29 Gy, 30-39 Gy, 40-49 Gy) increased after radiation therapy in all 41 patients.The mean SUVs after radiation therapy were 0.54, 0.68, 1.31, 1.74 and 2.27 for 0-9 Gy, 10-19 Gy, 20-29 Gy, 30-39 Gy and 40-49 Gy, respectively. Before the radiation therapy, the mean SUV in each region was 0.53, 0.52, 0.52, 0.53 and 0.54, respectively. These patients had significantly higher FDG activities in regions receiving 10 Gy or more (P <0.001).Compared with their counterparts, the elevation of SUV was significantly greater in those patients who developed acute RP subsequently.Conclusion The mean SUV of the lung tissue may be a useful predictor for the acute RR FDG-PET/CT may play a new role in the study of the radiation damage of the lung.

  8. Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Gross, N.J.; Holloway, N.O.; Narine, K.R. (Medical Radiology Service, Hines VA Hospital, Maywood, IL (United States))

    1991-09-01

    Corticosteroids have previously been found to be protective against the mortality of radiation pneumonitis in mice, even when given well after lethal lung irradiation. The authors explored the possibility that this effect was due to their well-known anti-inflammatory actions by giving various nonsteroidal inhibitors of arachidonate metabolism to groups of mice that had received 19 Gy to the thorax (bilaterally). Treatments of four cyclooxygenase inhibitors, one lipoxygenase inhibitor, and one leukotriene receptor antagonist, given by various routes in various doses, were commenced 10 weeks after irradiation or sham irradiation and continued throughout the period when death from radiation pneumonitis occurs, 11-26 weeks after irradiation. Each of the treatments had the appropriate effect on arachidonate metabolism in the lungs as assessed by LTB4 and PGE2 levels in lung lavage fluid. The principal end point was mortality. The 5-lipoxygenase inhibitor diethylcarbamazine and the LTD4/LTE4 receptor antagonist LY 171883 markedly reduced mortality in dose-response fashion. The effects of cyclooxygenase inhibitors were divergent; piroxicam and ibuprofen were marginally protective, indomethacin in all doses accelerated mortality, and aspirin reduced mortality in a dose-response fashion. These results suggest that the protective effect of corticosteroids in radiation pneumonitis can be tentatively attributed to their anti-inflammatory actions, and that nonsteroidal anti-inflammatory agents, particularly those that affect lipoxygenase products, may offer equal or better protection than corticosteroids against mortality due to radiation pneumonitis.

  9. Bronchiolitis obliterans organizing pneumonia after tangential beam irradiation to the breast. Discrimination from radiation pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Nambu, Atsushi; Ozawa, Katsura; Kanazawa, Masaki; Miyata, Kazuyuki [Kofu Municipal Hospital (Japan); Araki, Tsutomu; Ohki, Zennosuke [Yamanashi Medical Coll., Tamaho (Japan)

    2002-06-01

    We report a case of bronchiolitis obliterans organizing pneumonia (BOOP) secondary to tangential beam irradiation to the breast, which occurred seven months after the completion of radiotherapy. Although radiation pneumonitis is an alternative consideration, BOOP could be differentiated from it by its relatively late onset and extensive distribution, which did not respect the radiation field. This disease should always be kept in mind in patients with a history of tangential beam irradiation to the breast. (author)

  10. A case of radiation pneumonitis associated with high serum KL-6 levels

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Masamitsu; Yoshida, Kouichirou; Niki, Yoshihito; Manabe, Toshiaki; Matsushima, Toshiharu [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    1997-12-31

    A 65-year-old man was admitted to our hospital in January 1992 for chemotherapy and radiation therapy against primary lung cancer, which was diagnosed as a squamous cell carcinoma by a transbronchial lung biopsy. The lung tumor was decreased in size and he was discharged in May 1993. Twenty-five days after discharge, he experienced fever and dyspnea, and was readmitted to our hospital. His chest x-ray and laboratory data suggested that he had radiation pneumonitis and his serum KL-6 level was high. Despite the treatment with methylprednisolone, prednisolone and cyclophosphamide, his serum KL-6 levels rapidly increased and correlated with his serum LDH levels and reversely correlated with the levels of PaO{sub 2} and opacities on chest x-ray films. An autopsy revealed a diffuse alveolar damage with proliferated type II pneumocytes, which was consistent with radiation pneumonitis, but was not associated with any infectious lesions. The findings in this case suggest that the serum KL-6 could be consistently high and that KL-6 levels could be a useful monitoring marker for radiation pneumonitis. (author)

  11. Preventive effects of selenium-enriched spiruline (SESP) on radiation pneumonitis.

    Science.gov (United States)

    Bai, Y; Wang, D; Cui, X; Yang, Z; Zhu, M; Zhang, Z; Xia, G; Gong, Y

    1998-01-01

    We studied the early effects of selenium-enriched spiruline (SESP) on radiation-induced pulmonary fibrosis using histopathology, cDNA-mRNA dot-blot hybridization, and a biochemical technique for quantifying the hydroxyproline content. We found marked lung injury in the irradiated group, whereas only slight hyperemia, hemorrhage, exudation, and thickness of the interalveolar wall in the lung in the selenium-treated group. The hydroxyproline (hyp) content in the lungs and the synthesis of type III collagen mRNA decreased in the SESP-treated group. Selenium-enriched spiruline may have a protective effect on the development of radiation pneumonitis.

  12. Framework for radiation pneumonitis risk stratification based on anatomic and perfused lung dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Dhami, Gurleen; Zeng, Jing; Patel, Shilpen A.; Rengan, Ramesh [University of Washington School of Medicine, Department of Radiation Oncology, Seattle, WA (United States); Vesselle, Hubert J.; Kinahan, Paul E.; Miyaoka, Robert S. [University of Washington School of Medicine, Department of Radiology, Seattle, WA (United States); Bowen, Stephen R. [University of Washington School of Medicine, Department of Radiation Oncology, Seattle, WA (United States); University of Washington School of Medicine, Department of Radiology, Seattle, WA (United States)

    2017-05-15

    To design and apply a framework for predicting symptomatic radiation pneumonitis in patients undergoing thoracic radiation, using both pretreatment anatomic and perfused lung dose-volume parameters. Radiation treatment planning CT scans were coregistered with pretreatment [{sup 99m}Tc]MAA perfusion SPECT/CT scans of 20 patients who underwent definitive thoracic radiation. Clinical radiation pneumonitis was defined as grade ≥ 2 (CTCAE v4 grading system). Anatomic lung dose-volume parameters were collected from the treatment planning scans. Perfusion dose-volume parameters were calculated from pretreatment SPECT/CT scans. Equivalent doses in 2 Gy per fraction were calculated in the lung to account for differences in treatment regimens and spatial variations in lung dose (EQD2{sub lung}). Anatomic lung dosimetric parameters (MLD) and functional lung dosimetric parameters (pMLD{sub 70%}) were identified as candidate predictors of grade ≥ 2 radiation pneumonitis (AUC > 0.93, p < 0.01). Pairing of an anatomic and functional dosimetric parameter (e.g., MLD and pMLD{sub 70%}) may further improve prediction accuracy. Not all individuals with high anatomic lung dose (MLD > 13.6 GyEQD2{sub lung}, 19.3 Gy for patients receiving 60 Gy in 30 fractions) developed radiation pneumonitis, but all individuals who also had high mean dose to perfused lung (pMLD{sub 70%} > 13.3 GyEQD2) developed radiation pneumonitis. The preliminary application of this framework revealed differences between anatomic and perfused lung dosimetry in this limited patient cohort. The addition of perfused lung parameters may help risk stratify patients for radiation pneumonitis, especially in treatment plans with high anatomic mean lung dose. Further investigations are warranted. (orig.) [German] Erstellung und Anwendung eines Rahmenwerks zur Vorhersage symptomatischer Strahlenpneumonitis bei Patienten mit einer Thorax-Bestrahlung anhand anatomischer und perfundierter Lungendosis-Volumen-Parameter in der

  13. Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Pinnix, Chelsea C., E-mail: ccpinnix@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Smith, Grace L.; Milgrom, Sarah; Osborne, Eleanor M.; Reddy, Jay P.; Akhtari, Mani; Reed, Valerie; Arzu, Isidora; Allen, Pamela K.; Wogan, Christine F. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fanale, Michele A.; Oki, Yasuhiro; Turturro, Francesco; Romaguera, Jorge; Fayad, Luis; Fowler, Nathan; Westin, Jason; Nastoupil, Loretta; Hagemeister, Fredrick B.; Rodriguez, M. Alma [Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); and others

    2015-05-01

    Purpose: Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a single institution. Methods and Materials: We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP according to Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ{sup 2} test and logistic multivariate regression. Results: Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grades 1-3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation therapy (10%, P=.019). Several dosimetric parameters predicted RP, including mean lung dose of >13.5 Gy, V{sub 20} of >30%, V{sub 15} of >35%, V{sub 10} of >40%, and V{sub 5} of >55%. The likelihood ratio χ{sup 2} value was highest for V{sub 5} >55% (χ{sup 2} = 19.37). Conclusions: In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed

  14. Hypofractionation does not increase radiation pneumonitis risk with modern conformal radiation delivery techniques

    Energy Technology Data Exchange (ETDEWEB)

    Vogelius, Ivan S.; Westerly, David C.; Cannon, George M.; Bentzen, Soeren M. (Dept. of Human Oncology, Univ. of Wisconsin School of Medicine and Public Health, Madison, WI (United States)), E-mail: bentzen@humonc.wisc.edu

    2010-10-15

    Purpose. To study the interaction between radiation dose distribution and hypofractionated radiotherapy with respect to the risk of radiation pneumonitis (RP) estimated from normal tissue complication probability (NTCP) models. Material and methods. Eighteen non-small cell lung cancer patients previously treated with helical tomotherapy were selected. For each patient a 3D-conformal plan (3D-CRT) plan was produced in addition to the delivered plan. The standard fractionation schedule was set to 60 Gy in 30 fractions. Iso-efficacy comparisons with hypofractionation were performed by changing the fractionation and the physical prescription dose while keeping the equivalent tumor dose in 2 Gy fractions constant. The risk of developing RP after radiotherapy was estimated using the Mean Equivalent Lung Dose in 2-Gy fractions (MELD2) NTCP model with alpha/beta=4 Gy for the residual lung. Overall treatment time was kept constant. Results. The mean risk of clinical RP after standard fractionation was 7.6% for Tomotherapy (range: 2.8-15.9%) and 9.2% for 3D-CRT (range 3.2-20.2%). Changing to 20 fractions, the Tomotherapy plans became slightly less toxic if the tumor alpha/beta ratio, (alpha/beta)T, was 7 Gy (mean RP risk 7.5%, range 2.8-16%) while the 3D-CRT plans became marginally more toxic (mean RP risk 9.8%, range 3.2-21%). If (alpha/beta)T was 13 Gy, the mean estimated risk of RP is 7.9% for Tomotherapy (range: 2.8-17%) and 10% for 3D-CRT (range 3.2-22%). Conclusion. Modern highly conformal dose distributions are radiobiologically more forgiving with respect to hypofractionation, even for a normal tissue endpoint where alpha/beta is lower than for the tumor in question.

  15. Acute Radiation Syndrome

    Science.gov (United States)

    ... Matters Information on Specific Types of Emergencies Acute Radiation Syndrome (ARS): A Fact Sheet for the Public ... is called the radiation dose. People exposed to radiation will get ARS only if: The radiation dose ...

  16. Combining multiple models to generate consensus: Application to radiation-induced pneumonitis prediction

    Science.gov (United States)

    Das, Shiva K.; Chen, Shifeng; Deasy, Joseph O.; Zhou, Sumin; Yin, Fang-Fang; Marks, Lawrence B.

    2008-01-01

    The fusion of predictions from disparate models has been used in several fields to obtain a more realistic and robust estimate of the “ground truth” by allowing the models to reinforce each other when consensus exists, or, conversely, negate each other when there is no consensus. Fusion has been shown to be most effective when the models have some complementary strengths arising from different approaches. In this work, we fuse the results from four common but methodologically different nonlinear multivariate models (Decision Trees, Neural Networks, Support Vector Machines, Self-Organizing Maps) that were trained to predict radiation-induced pneumonitis risk on a database of 219 lung cancer patients treated with radiotherapy (34 with Grade 2+ postradiotherapy pneumonitis). Each model independently incorporated a small number of features from the available set of dose and nondose patient variables to predict pneumonitis; no two models had all features in common. Fusion was achieved by simple averaging of the predictions for each patient from all four models. Since a model’s prediction for a patient can be dependent on the patient training set used to build the model, the average of several different predictions from each model was used in the fusion (predictions were made by repeatedly testing each patient with a model built from different cross-validation training sets that excluded the patient being tested). The area under the receiver operating characteristics curve for the fused cross-validated results was 0.79, with lower variance than the individual component models. From the fusion, five features were extracted as the consensus among all four models in predicting radiation pneumonitis. Arranged in order of importance, the features are (1) chemotherapy; (2) equivalent uniform dose (EUD) for exponent a=1.2 to 3; (3) EUD for a=0.5 to 1.2, lung volume receiving >20–30 Gy; (4) female sex; and (5) squamous cell histology. To facilitate ease of interpretation

  17. Combining multiple models to generate consensus: Application to radiation-induced pneumonitis prediction

    Energy Technology Data Exchange (ETDEWEB)

    Das, Shiva K.; Chen Shifeng; Deasy, Joseph O.; Zhou Sumin; Yin Fangfang; Marks, Lawrence B. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri 63110 (United States); Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 (United States)

    2008-11-15

    The fusion of predictions from disparate models has been used in several fields to obtain a more realistic and robust estimate of the ''ground truth'' by allowing the models to reinforce each other when consensus exists, or, conversely, negate each other when there is no consensus. Fusion has been shown to be most effective when the models have some complementary strengths arising from different approaches. In this work, we fuse the results from four common but methodologically different nonlinear multivariate models (Decision Trees, Neural Networks, Support Vector Machines, Self-Organizing Maps) that were trained to predict radiation-induced pneumonitis risk on a database of 219 lung cancer patients treated with radiotherapy (34 with Grade 2+ postradiotherapy pneumonitis). Each model independently incorporated a small number of features from the available set of dose and nondose patient variables to predict pneumonitis; no two models had all features in common. Fusion was achieved by simple averaging of the predictions for each patient from all four models. Since a model's prediction for a patient can be dependent on the patient training set used to build the model, the average of several different predictions from each model was used in the fusion (predictions were made by repeatedly testing each patient with a model built from different cross-validation training sets that excluded the patient being tested). The area under the receiver operating characteristics curve for the fused cross-validated results was 0.79, with lower variance than the individual component models. From the fusion, five features were extracted as the consensus among all four models in predicting radiation pneumonitis. Arranged in order of importance, the features are (1) chemotherapy; (2) equivalent uniform dose (EUD) for exponent a=1.2 to 3; (3) EUD for a=0.5 to 1.2, lung volume receiving >20-30 Gy; (4) female sex; and (5) squamous cell histology. To facilitate

  18. Internal Mammary Lymph Node Irradiation after Breast Conservation Surgery: Radiation Pneumonitis versus Dose-Volume Histogram Parameters

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Joo Young; Lee, Ik Jae; Keum, Ki Chang; Kim, Yong Bae; Shim, Su Jung; Jeong, Kyoung Keun; Kim, Jong Dae; Suh, Chang Ok [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-12-15

    Purpose: To evaluate the association between radiation pneumonitis and dose-volume histogram parameters and to provide practical guidelines to prevent radiation pneumonitis following radiotherapy administered for breast cancer including internal mammary lymph nodes. Materials and Methods: Twenty patients with early breast cancer who underwent a partial mastectomy were involved in this study. The entire breast, supraclavicular lymph nodes, and internal mammary lymph nodes were irradiated with a dose of 50.4 Gy in 28 fractions. Radiation pneumonitis was assessed by both radiological pulmonary change (RPC) and by evaluation of symptomatic radiation pneumonitis. Dose-volume histogram parameters were compared between patients with grade <2 RPC and those with grade {>=}2 RPC. The parameters were the mean lung dose, V10 (percent lung volume receiving equal to and more than 10 Gy), V20, V30, V40, and normal tissue complication probability (NTCP). Results: Of the 20 patients, 9 (45%) developed grade 2 RPC and 11 (55%) did not develop RPC (grade 0). Only one patient developed grade 1 symptomatic radiation pneumonitis. Univariate analysis showed that among the dose-volume histogram parameters, NTCP was significantly different between the two RPC grade groups (p <0.05). Fisher's exact test indicated that an NTCP value of 45% was appropriate as an RPC threshold level. Conclusion: This study shows that NTCP can be used as a predictor of RPC after radiotherapy of the internal mammary lymph nodes in breast cancer. Clinically, it indicates that an RPC is likely to develop when the NTCP is greater than 45%.

  19. Towards individualized dose constraints: Adjusting the QUANTEC radiation pneumonitis model for clinical risk factors

    DEFF Research Database (Denmark)

    Appelt, Ane L; Vogelius, Ivan R.; Farr, Katherina P.

    2014-01-01

    Background. Understanding the dose-response of the lung in order to minimize the risk of radiation pneumonitis (RP) is critical for optimization of lung cancer radiotherapy. We propose a method to combine the dose-response relationship for RP in the landmark QUANTEC paper with known clinical risk......-only QUANTEC model and the model including risk factors. Subdistribution cumulative incidence functions were compared for patients with high/low-risk predictions from the two models, and concordance indices (c-indices) for the prediction of RP were calculated. Results. The reference dose- response relationship...... factors, in order to enable individual risk prediction. The approach is validated in an independent dataset. Material and methods. The prevalence of risk factors in the patient populations underlying the QUANTEC analysis was estimated, and a previously published method to adjust dose...

  20. Refractory acute respiratory failure due to Pneumocystis jiroveci (PCP) and Cytomegalovirus (CMV) pneumonitis: A case report and review of literature.

    Science.gov (United States)

    Shah, Kairav; Cherabuddi, Kartikeya; Beal, Stacy G; Kalyatanda, Gautam

    2017-01-01

    Opportunistic infections with Pneumocystis jiroveci pneumonia (PCP) are common in patients with HIV (human immunodeficiency virus) and are encountered once the CD4 count decreases below 200 cells/mm3. Cytomegalovirus (CMV) tends to cause disease once the CD4 count drops below 50 cells/mm3. CMV pneumonitis is not common in this population. However, detecting its presence in broncho-alveolar lavage (BAL) fluid has been associated with increased morbidity and mortality. The role of antiviral therapy against CMV remains unclear. We report a newly diagnosed HIV patient with a CD4 count of 44 cells/mm3 presenting with acute respiratory failure secondary to PCP that failed to respond to 3 weeks of standard therapy with trimethoprim-sulfamethoxazole and corticosteroids. He was later diagnosed to have a CMV co-infection causing pneumonitis with BAL cytology findings showing CMV cytopathic effects and PCP. Plasma CMV DNA PCR was 17,424 copies/mL. He responded well after introduction of intravenous ganciclovir. The presence of histopathologic changes demonstrating viral cytopathic effects on BAL cytology along with a high plasma CMV DNA PCR should raise the specificity for diagnosing CMV pneumonitis. True PCP and CMV pneumonitis can occur, and the addition of antiviral therapy with ganciclovir may benefit such patients in the right clinical scenario.

  1. Human Herpesvirus-6 Pneumonitis around the Engraftment of Cord Blood Transplantation following Foscarnet Prophylaxis in a Patient with Acute Leukemia

    Directory of Open Access Journals (Sweden)

    Takashi Ishio

    2015-01-01

    Full Text Available Human herpesvirus-6 (HHV-6 reactivation is sometimes observed in immunocompromised patients, especially after allogeneic stem cell transplantation. The complications of HHV-6 reactivation in this setting are mainly recognized as HHV-6 encephalitis. We herein report the case of a patient who developed HHV-6 pneumonitis after cord blood transplantation (CBT. A 35-year-old male underwent CBT for T-cell/myeloid mixed phenotype acute leukemia and achieved neutrophil engraftment on day 31. He had received foscarnet as prophylaxis for HHV-6 reactivation. A computed tomography (CT scan to evaluate the leukemic tumor showed bilateral interstitial pneumonitis on day 33, although he had no respiratory symptoms. The findings of the CT scan were consistent with those of HHV-6 pneumonitis that were reported previously. HHV-6 DNA, but no other pathogens, was detected in his bronchoalveolar lavage (BAL fluid. The patient was successfully treated with a therapeutic dose of foscarnet. This case indicates that performing a CT scan around the time of neutrophil engraftment can play an important role in detecting the early phase of HHV-6 pneumonia, and BAL should be considered if features consistent with HHV-6 pneumonitis are observed in patients with a risk of HHV-6 reactivation.

  2. Alterations in pulmonary surfactant protein a metabolism and its diagnostic value in onset of radiation pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Imai, Yoshinari; Takahashi, Hiroki [Sapporo Medical Univ. (Japan)

    1999-12-01

    Radiation pneumonitis (RP) is a serious disorder caused by radiation therapy, for the detection of which there exists no simple and sensitive clinical examination. In this study, we examined whether the measurement of serum pulmonary surfactant protein A (SP-A) levels could be effective for detecting the onset of RP. Of the 18 patients included in the study, 9 suffered RP complication after radiation therapy. Serum SP-A levels in patients with RP (64.1{+-}6.5 ng/ml) were 1.82 times as high as those of pre-radiation (36.2{+-}4.0 ng/ml). The difference between them was significant (p=0.0003), while the SP-A value in patients without RP after radiation therapy was almost the same as the pre-radiation level. To study the mechanisms of these elevations, we developed a model of whole lung irradiation (20 Gy) in adult rats. Prior to alveolitis, which was a histological change seen at day 28, levels of SP-A in lung tissue homogenates and bronchoalveolar lavage fluid had become elevated by day 21. Serum SP-A levels in the irradiated rats were significantly elevated by day 21, peaking at day 35, and then declined. Hydroxyproline contents in lung tissues were elevated by day 42 and remained so through day 56. Therefore, the increase in serum SP-A level may be reflected by alveolitis but not fibrosis. In conclusion, determination of serum SP-A could be helpful in detecting the onset of RP. (author)

  3. Enhanced survival from radiation pneumonitis by combined irradiation to the skin.

    Science.gov (United States)

    Gao, Feng; Fish, Brian L; Szabo, Aniko; Schock, Ashley; Narayanan, Jayashree; Jacobs, Elizabeth R; Moulder, John E; Lazarova, Zelmira; Medhora, Meetha

    2014-09-01

    To develop mitigators for combined irradiation to the lung and skin. Rats were treated with X-rays as follows: (1) 12.5 or 13 Gy whole thorax irradiation (WTI); (2) 30 Gy soft X-rays to 10% area of the skin only; (3) 12.5 or 13 Gy WTI + 30 Gy skin irradiation after 3 hours; (4) 12.5 Gy WTI + skin irradiation and treated with captopril (160 mg/m(2)/day) started after 7 days. Our end points were survival (primary) based on IACUC euthanization criteria and secondary measurements of breathing intervals and skin injury. Lung collagen at 210 days was measured in rats surviving 13 Gy WTI. After 12.5 Gy WTI with or without skin irradiation, one rat (12.5 Gy WTI) was euthanized. Survival was less than 10% in rats receiving 13 Gy WTI, but was enhanced when combined with skin irradiation (p WTI vs. 13 Gy WTI + 30 Gy skin irradiation (p WTI + 30 Gy skin irradiation (p = 0.008). Radiation to the skin given 3 h after WTI mitigated morbidity during pneumonitis in rats. Captopril enhanced the rate of healing of radiation-dermatitis after combined irradiations to the thorax and skin.

  4. Primary Sjogren’s Syndrome Presenting as Acute Interstitial Pneumonitis/Hamman-Rich Syndrome

    Directory of Open Access Journals (Sweden)

    Abidullah Khan

    2016-01-01

    Full Text Available A previously well, 45-year-old Pakistani lady was admitted to the medical unit on-call of Khyber Teaching Hospital (KTH Peshawar with a 5-day history of fever, productive cough with copious mucoid sputum, dyspnea, and pleuritic chest pain. She also complained of dry eyes, mouth, and vagina. Her chest X-ray showed diffuse alveolar shadowing and arterial gas analysis confirmed type 1 respiratory failure. Over the next few days, she deteriorated rapidly making an urgent transfer to the medical intensive care unit (MICU necessary, where she was mechanically ventilated. An HRCT followed by bronchoscopic biopsies made a diagnosis of acute interstitial pneumonitis (AIP, formerly known as Hamman-Rich syndrome. She also turned out to be positive for both anti-SS-A/Ro and anti-SS-B/La antibodies along with a positive Schirmer’s test and lower lip biopsy. She received intravenous steroids and supportive care. The patient had a complete recovery after approximately three weeks’ stay in the hospital with lung function returning back to normal. This is most probably the first ever case of primary Sjogren syndrome (pSjS presenting as AIP, recovering completely in less than a month time.

  5. Primary Sjogren's Syndrome Presenting as Acute Interstitial Pneumonitis/Hamman-Rich Syndrome

    Science.gov (United States)

    Humayun, Mohammad; Haider, Iqbal; Ayub, Maimoona; Shah, Zakir; Ajmal, Fahad

    2016-01-01

    A previously well, 45-year-old Pakistani lady was admitted to the medical unit on-call of Khyber Teaching Hospital (KTH) Peshawar with a 5-day history of fever, productive cough with copious mucoid sputum, dyspnea, and pleuritic chest pain. She also complained of dry eyes, mouth, and vagina. Her chest X-ray showed diffuse alveolar shadowing and arterial gas analysis confirmed type 1 respiratory failure. Over the next few days, she deteriorated rapidly making an urgent transfer to the medical intensive care unit (MICU) necessary, where she was mechanically ventilated. An HRCT followed by bronchoscopic biopsies made a diagnosis of acute interstitial pneumonitis (AIP), formerly known as Hamman-Rich syndrome. She also turned out to be positive for both anti-SS-A/Ro and anti-SS-B/La antibodies along with a positive Schirmer's test and lower lip biopsy. She received intravenous steroids and supportive care. The patient had a complete recovery after approximately three weeks' stay in the hospital with lung function returning back to normal. This is most probably the first ever case of primary Sjogren syndrome (pSjS) presenting as AIP, recovering completely in less than a month time. PMID:27818685

  6. Uncommon appearance of radiation-induced pneumonitis during radiotherapy of patients with small-cell bronchiogenic carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Karstens, J.H.; Ammon, J.; Frik, W.

    1982-10-15

    Four cases of distinctive radiation-induced pneumonitis with severe clinical symptoms were observed during combined therapy of 52 patients with small-cell bronchial carcinoma. Withdrawal of corticosteroids was identified as the most probable cause, due to the fact that a time correlation between cortison withdrawal and the onset of clinical symptoms was found in all four patients. Possible consequences for future therapy measures are pointed out.

  7. Predicting Radiation Pneumonitis After Stereotactic Ablative Radiation Therapy in Patients Previously Treated With Conventional Thoracic Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Liu Hui; Zhang Xu [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Vinogradskiy, Yevgeniy Y. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Swisher, Stephen G. [Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Joe Y., E-mail: jychang@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-11-15

    Purpose: To determine the incidence of and risk factors for radiation pneumonitis (RP) after stereotactic ablative radiation therapy (SABR) to the lung in patients who had previously undergone conventional thoracic radiation therapy. Methods and Materials: Seventy-two patients who had previously received conventionally fractionated radiation therapy to the thorax were treated with SABR (50 Gy in 4 fractions) for recurrent disease or secondary parenchymal lung cancer (T <4 cm, N0, M0, or Mx). Severe (grade {>=}3) RP and potential predictive factors were analyzed by univariate and multivariate logistic regression analyses. A scoring system was established to predict the risk of RP. Results: At a median follow-up time of 16 months after SABR (range, 4-56 months), 15 patients had severe RP (14 [18.9%] grade 3 and 1 [1.4%] grade 5) and 1 patient (1.4%) had a local recurrence. In univariate analyses, Eastern Cooperative Oncology Group performance status (ECOG PS) before SABR, forced expiratory volume in 1 second (FEV1), and previous planning target volume (PTV) location were associated with the incidence of severe RP. The V{sub 10} and mean lung dose (MLD) of the previous plan and the V{sub 10}-V{sub 40} and MLD of the composite plan were also related to RP. Multivariate analysis revealed that ECOG PS scores of 2-3 before SABR (P=.009), FEV1 {<=}65% before SABR (P=.012), V{sub 20} {>=}30% of the composite plan (P=.021), and an initial PTV in the bilateral mediastinum (P=.025) were all associated with RP. Conclusions: We found that severe RP was relatively common, occurring in 20.8% of patients, and could be predicted by an ECOG PS score of 2-3, an FEV1 {<=}65%, a previous PTV spanning the bilateral mediastinum, and V{sub 20} {>=}30% on composite (previous RT+SABR) plans. Prospective studies are needed to validate these predictors and the scoring system on which they are based.

  8. Serum Amyloid A as a Predictive Marker for Radiation Pneumonitis in Lung Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yu-Shan [Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Department of Animal Science, National Ilan University, Ilan, Taiwan (China); Chang, Heng-Jui [Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Chang, Yue-Cune [Department of Mathematics, Tamkang University, Taipei, Taiwan (China); Huang, Su-Chen; Ko, Hui-Ling; Chang, Chih-Chia [Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Yeh, Yu-Wung; Jiang, Jiunn-Song [Department of Chest Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Lee, Cheng-Yen; Chi, Mau-Shin [Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Chi, Kwan-Hwa, E-mail: M006565@ms.skh.org.tw [Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Institute of Radiation Science and School of Medicine, National Yang-Ming University, Taipei, Taiwan (China)

    2013-03-01

    Purpose: To investigate serum markers associated with radiation pneumonitis (RP) grade ≥3 in patients with lung cancer who were treated with radiation therapy. Methods and Materials: Pretreatment serum samples from patients with stage Ib-IV lung cancer who developed RP within 1 year after radiation therapy were analyzed to identify a proteome marker able to stratify patients prone to develop severe RP by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Dosimetric parameters and 3 biological factors were compared. Results: Serum samples from 16 patients (28%) with severe RP (grade 3-4) and 42 patients (72%) with no or mild RP (grade 0-2) were collected for analysis. All patients received a median of 54 Gy (range, 42-70 Gy) of three-dimensional conformal radiation therapy with a mean lung dose (MLD) of 1502 cGy (range, 700-2794 cGy). An m/z peak of 11,480 Da was identified by SELDI-TOF-MS, and serum amyloid A (SAA) was the primary splitter serum marker. The receiver operating characteristic area under the curve of SAA (0.94; 95% confidence interval [CI], 0.87-1.00) was higher than those of C-reactive protein (0.83; 95% CI, 0.72-0.94), interleukin-6 (0.79; 95% CI, 0.65-0.94), and MLD (0.57; 95% CI, 0.37-0.77). The best sensitivity and specificity of combined SAA and MLD for predicting RP were 88.9% and 96.0%, respectively. Conclusions: Baseline SAA could be used as an auxiliary marker for predicting severe RP. Extreme care should be taken to limit the lung irradiation dose in patients with high SAA.

  9. Towards individualized dose constraints: Adjusting the QUANTEC radiation pneumonitis model for clinical risk factors

    DEFF Research Database (Denmark)

    Appelt, Ane L; Vogelius, Ivan R.; Farr, Katherina P.;

    2014-01-01

    Background. Understanding the dose-response of the lung in order to minimize the risk of radiation pneumonitis (RP) is critical for optimization of lung cancer radiotherapy. We propose a method to combine the dose-response relationship for RP in the landmark QUANTEC paper with known clinical risk...... factors, in order to enable individual risk prediction. The approach is validated in an independent dataset. Material and methods. The prevalence of risk factors in the patient populations underlying the QUANTEC analysis was estimated, and a previously published method to adjust dose......-response relationships for clinical risk factors was employed. Effect size estimates (odds ratios) for risk factors were drawn from a recently published meta-analysis. Baseline values for D50 and γ50 were found. The method was tested in an independent dataset (103 patients), comparing the predictive power of the dose......-only QUANTEC model and the model including risk factors. Subdistribution cumulative incidence functions were compared for patients with high/low-risk predictions from the two models, and concordance indices (c-indices) for the prediction of RP were calculated. Results. The reference dose- response relationship...

  10. Modeling of Radiation Pneumonitis after Lung Stereotactic Body Radiotherapy: A Bayesian Network Approach

    CERN Document Server

    Lee, Sangkyu; Jeyaseelan, Krishinima; Faria, Sergio; Kopek, Neil; Brisebois, Pascale; Vu, Toni; Filion, Edith; Campeau, Marie-Pierre; Lambert, Louise; Del Vecchio, Pierre; Trudel, Diane; El-Sokhn, Nidale; Roach, Michael; Robinson, Clifford; Naqa, Issam El

    2015-01-01

    Background and Purpose: Stereotactic body radiotherapy (SBRT) for lung cancer accompanies a non-negligible risk of radiation pneumonitis (RP). This study presents a Bayesian network (BN) model that connects biological, dosimetric, and clinical RP risk factors. Material and Methods: 43 non-small-cell lung cancer patients treated with SBRT with 5 fractions or less were studied. Candidate RP risk factors included dose-volume parameters, previously reported clinical RP factors, 6 protein biomarkers at baseline and 6 weeks post-treatment. A BN ensemble model was built from a subset of the variables in a training cohort (N=32), and further tested in an independent validation cohort (N=11). Results: Key factors identified in the BN ensemble for predicting RP risk were ipsilateral V5, lung volume receiving more than 105% of prescription, and decrease in angiotensin converting enzyme (ACE) from baseline to 6 weeks. External validation of the BN ensemble model yielded an area under the curve of 0.8. Conclusions: The BN...

  11. Using machine learning to predict radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy

    Science.gov (United States)

    Valdes, Gilmer; Solberg, Timothy D.; Heskel, Marina; Ungar, Lyle; Simone, Charles B., II

    2016-08-01

    To develop a patient-specific ‘big data’ clinical decision tool to predict pneumonitis in stage I non-small cell lung cancer (NSCLC) patients after stereotactic body radiation therapy (SBRT). 61 features were recorded for 201 consecutive patients with stage I NSCLC treated with SBRT, in whom 8 (4.0%) developed radiation pneumonitis. Pneumonitis thresholds were found for each feature individually using decision stumps. The performance of three different algorithms (Decision Trees, Random Forests, RUSBoost) was evaluated. Learning curves were developed and the training error analyzed and compared to the testing error in order to evaluate the factors needed to obtain a cross-validated error smaller than 0.1. These included the addition of new features, increasing the complexity of the algorithm and enlarging the sample size and number of events. In the univariate analysis, the most important feature selected was the diffusion capacity of the lung for carbon monoxide (DLCO adj%). On multivariate analysis, the three most important features selected were the dose to 15 cc of the heart, dose to 4 cc of the trachea or bronchus, and race. Higher accuracy could be achieved if the RUSBoost algorithm was used with regularization. To predict radiation pneumonitis within an error smaller than 10%, we estimate that a sample size of 800 patients is required. Clinically relevant thresholds that put patients at risk of developing radiation pneumonitis were determined in a cohort of 201 stage I NSCLC patients treated with SBRT. The consistency of these thresholds can provide radiation oncologists with an estimate of their reliability and may inform treatment planning and patient counseling. The accuracy of the classification is limited by the number of patients in the study and not by the features gathered or the complexity of the algorithm.

  12. Developing Multivariable Normal Tissue Complication Probability Model to Predict the Incidence of Symptomatic Radiation Pneumonitis among Breast Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Tsair-Fwu Lee

    Full Text Available Symptomatic radiation pneumonitis (SRP, which decreases quality of life (QoL, is the most common pulmonary complication in patients receiving breast irradiation. If it occurs, acute SRP usually develops 4-12 weeks after completion of radiotherapy and presents as a dry cough, dyspnea and low-grade fever. If the incidence of SRP is reduced, not only the QoL but also the compliance of breast cancer patients may be improved. Therefore, we investigated the incidence SRP in breast cancer patients after hybrid intensity modulated radiotherapy (IMRT to find the risk factors, which may have important effects on the risk of radiation-induced complications.In total, 93 patients with breast cancer were evaluated. The final endpoint for acute SRP was defined as those who had density changes together with symptoms, as measured using computed tomography. The risk factors for a multivariate normal tissue complication probability model of SRP were determined using the least absolute shrinkage and selection operator (LASSO technique.Five risk factors were selected using LASSO: the percentage of the ipsilateral lung volume that received more than 20-Gy (IV20, energy, age, body mass index (BMI and T stage. Positive associations were demonstrated among the incidence of SRP, IV20, and patient age. Energy, BMI and T stage showed a negative association with the incidence of SRP. Our analyses indicate that the risk of SPR following hybrid IMRT in elderly or low-BMI breast cancer patients is increased once the percentage of the ipsilateral lung volume receiving more than 20-Gy is controlled below a limitation.We suggest to define a dose-volume percentage constraint of IV20< 37% (or AIV20< 310cc for the irradiated ipsilateral lung in radiation therapy treatment planning to maintain the incidence of SPR below 20%, and pay attention to the sequelae especially in elderly or low-BMI breast cancer patients. (AIV20: the absolute ipsilateral lung volume that received more than

  13. Acute local radiation injuries

    Energy Technology Data Exchange (ETDEWEB)

    Gongora, R. (Institut Curie, 75 - Paris (France)); Jammet, H. (Commissariat a l' Energie Atomique, ISPN, 92 - Fontenay-aux-Roses (France))

    1983-01-01

    Local acute radiation injuries do not occur very often. Their origin is generally accidental. They show specific anatomo-clinical features. The clinical evolution and therapeutic behaviour are dependent on the dose level and topographical distribution. The dosimetric assessment requires physical methods and paraclinical investigations. From a study of 60 cases followed by the International Center of Radiopathology, the clinical symptomatology is described and the problems raised to the radiopathologist physician by local acute radiation injuries are stated.

  14. Incorporating Single-nucleotide Polymorphisms Into the Lyman Model to Improve Prediction of Radiation Pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, Susan L., E-mail: sltucker@mdanderson.org [Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Li Minghuan [Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong (China); Xu Ting; Gomez, Daniel [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Yuan Xianglin [Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Yu Jinming [Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong (China); Liu Zhensheng; Yin Ming; Guan Xiaoxiang; Wang Lie; Wei Qingyi [Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Vinogradskiy, Yevgeniy [University of Colorado School of Medicine, Aurora, Colorado (United States); Martel, Mary [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-01-01

    Purpose: To determine whether single-nucleotide polymorphisms (SNPs) in genes associated with DNA repair, cell cycle, transforming growth factor-{beta}, tumor necrosis factor and receptor, folic acid metabolism, and angiogenesis can significantly improve the fit of the Lyman-Kutcher-Burman (LKB) normal-tissue complication probability (NTCP) model of radiation pneumonitis (RP) risk among patients with non-small cell lung cancer (NSCLC). Methods and Materials: Sixteen SNPs from 10 different genes (XRCC1, XRCC3, APEX1, MDM2, TGF{beta}, TNF{alpha}, TNFR, MTHFR, MTRR, and VEGF) were genotyped in 141 NSCLC patients treated with definitive radiation therapy, with or without chemotherapy. The LKB model was used to estimate the risk of severe (grade {>=}3) RP as a function of mean lung dose (MLD), with SNPs and patient smoking status incorporated into the model as dose-modifying factors. Multivariate analyses were performed by adding significant factors to the MLD model in a forward stepwise procedure, with significance assessed using the likelihood-ratio test. Bootstrap analyses were used to assess the reproducibility of results under variations in the data. Results: Five SNPs were selected for inclusion in the multivariate NTCP model based on MLD alone. SNPs associated with an increased risk of severe RP were in genes for TGF{beta}, VEGF, TNF{alpha}, XRCC1 and APEX1. With smoking status included in the multivariate model, the SNPs significantly associated with increased risk of RP were in genes for TGF{beta}, VEGF, and XRCC3. Bootstrap analyses selected a median of 4 SNPs per model fit, with the 6 genes listed above selected most often. Conclusions: This study provides evidence that SNPs can significantly improve the predictive ability of the Lyman MLD model. With a small number of SNPs, it was possible to distinguish cohorts with >50% risk vs <10% risk of RP when they were exposed to high MLDs.

  15. Regional Radiation Pneumonitis After SIRT of a Subcapsular Liver Metastasis: What is the Effect of Direct Beta Irradiation?

    Energy Technology Data Exchange (ETDEWEB)

    Dobrocky, Tomas, E-mail: tomas.dobrocky@insel.ch [University of Bern, Department of Interventional, Pediatric and Diagnostic Radiology, Inselspital, University Hospital (Switzerland); Fuerstner, Markus, E-mail: markus.fuerstner@insel.ch; Klaeser, Bernd, E-mail: bernd.klaeser@insel.ch [University of Bern, Department of Nuclear Medicine, Inselspital, University Hospital (Switzerland); Lopez-Benitez, Ruben, E-mail: ruben.lopez@insel.ch [University of Bern, Department of Interventional, Pediatric and Diagnostic Radiology, Inselspital, University Hospital (Switzerland); Wälti, Yara Banz, E-mail: yara.banz@pathology.unibe.ch [University of Bern, Institute of Pathology, University Hospital (Switzerland); Kara, Levent, E-mail: levent.kara@insel.ch [University of Bern, Department of Interventional, Pediatric and Diagnostic Radiology, Inselspital, University Hospital (Switzerland)

    2015-08-15

    We herein present a patient undergoing selective internal radiation therapy with an almost normal lung shunt fraction of 11.5 %, developing histologically proven radiation pneumonitis. Due to a predominance of pulmonary consolidations in the right lower lung and its proximity to a large liver metastases located in the dome of the right liver lobe a Monte Carlo simulation was performed to estimate the effect of direct irradiation of the lung parenchyma. According to our calculations direct irradiation seems negligible and RP is almost exclusively due to ectopic draining of radioactive spheres.

  16. A Combination of Podophyllotoxin and Rutin Alleviates Radiation-Induced Pneumonitis and Fibrosis through Modulation of Lung Inflammation in Mice

    Science.gov (United States)

    Verma, Savita; Kalita, Bhargab; Bajaj, Sania; Prakash, Hridayesh; Singh, Ajay Kumar; Gupta, Manju Lata

    2017-01-01

    Pneumonitis and pulmonary fibrosis are predominant consequences of radiation exposure, whether planned or accidental. The present study, demonstrates radioprotective potential of a formulation, prepared by combining podophyllotoxin and rutin (G-003M), in mice exposed to 11 Gy thoracic gamma radiation (TGR). Treated mice were observed for survival and other symptomatic features. Formation of reactive oxygen species (ROS)/nitric oxide (NO) was measured in bronchoalveolar lavage cells. DNA damage and cell death were assessed in alveolar cells by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Total protein (TP), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) were measured in bronchoalveolar lavage fluid (BALF)/serum of mice to assess lung vascular permeability. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), cluster of differentiation 45, inducible nitric oxide synthase (iNOS), and nitrotyrosine were also estimated in lungs/BALF of differentially treated mice. Our observations revealed 100% survival in G-003M-pretreated mice against 66.50% in 11 Gy TGR exposed. Other symptoms like reduction in graying of hair, weight loss, and breathing rate were also observed in pretreated groups. Significant decline in ROS/NO and cell death in formulation pretreated mice were also observed. Decreased level of TP, LDH, and ALP in BALF/serum samples revealed G-003M-induced inhibition in lung permeability. Level of IL-6, TNF-α, and TGF-β1 in the lungs of these mice was found corresponding to control group at 8 weeks posttreatment. On the contrary, these cytokines raised significantly in 11 Gy TGR-exposed mice. Lung pneumonitis and fibrosis were found significantly countered in these mice. The observations revealed that G-003M could regulate immune system by curtailing radiation-induced oxidative and inflammatory stress, which has helped in minimizing radiation-inflicted pneumonitis and

  17. TU-CD-BRB-01: Normal Lung CT Texture Features Improve Predictive Models for Radiation Pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Krafft, S [The University of Texas MD Anderson Cancer Center, Houston, TX (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, TX (United States); Briere, T; Court, L; Martel, M [The University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: Existing normal tissue complication probability (NTCP) models for radiation pneumonitis (RP) traditionally rely on dosimetric and clinical data but are limited in terms of performance and generalizability. Extraction of pre-treatment image features provides a potential new category of data that can improve NTCP models for RP. We consider quantitative measures of total lung CT intensity and texture in a framework for prediction of RP. Methods: Available clinical and dosimetric data was collected for 198 NSCLC patients treated with definitive radiotherapy. Intensity- and texture-based image features were extracted from the T50 phase of the 4D-CT acquired for treatment planning. A total of 3888 features (15 clinical, 175 dosimetric, and 3698 image features) were gathered and considered candidate predictors for modeling of RP grade≥3. A baseline logistic regression model with mean lung dose (MLD) was first considered. Additionally, a least absolute shrinkage and selection operator (LASSO) logistic regression was applied to the set of clinical and dosimetric features, and subsequently to the full set of clinical, dosimetric, and image features. Model performance was assessed by comparing area under the curve (AUC). Results: A simple logistic fit of MLD was an inadequate model of the data (AUC∼0.5). Including clinical and dosimetric parameters within the framework of the LASSO resulted in improved performance (AUC=0.648). Analysis of the full cohort of clinical, dosimetric, and image features provided further and significant improvement in model performance (AUC=0.727). Conclusions: To achieve significant gains in predictive modeling of RP, new categories of data should be considered in addition to clinical and dosimetric features. We have successfully incorporated CT image features into a framework for modeling RP and have demonstrated improved predictive performance. Validation and further investigation of CT image features in the context of RP NTCP

  18. Bayesian network ensemble as a multivariate strategy to predict radiation pneumonitis risk

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sangkyu, E-mail: sangkyu.lee@mail.mcgill.ca; Ybarra, Norma; Jeyaseelan, Krishinima; Seuntjens, Jan; El Naqa, Issam [Medical Physics Unit, McGill University, Montreal, Quebec H3G1A4 (Canada); Faria, Sergio; Kopek, Neil; Brisebois, Pascale [Department of Radiation Oncology, Montreal General Hospital, Montreal, H3G1A4 (Canada); Bradley, Jeffrey D.; Robinson, Clifford [Radiation Oncology, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110 (United States)

    2015-05-15

    Purpose: Prediction of radiation pneumonitis (RP) has been shown to be challenging due to the involvement of a variety of factors including dose–volume metrics and radiosensitivity biomarkers. Some of these factors are highly correlated and might affect prediction results when combined. Bayesian network (BN) provides a probabilistic framework to represent variable dependencies in a directed acyclic graph. The aim of this study is to integrate the BN framework and a systems’ biology approach to detect possible interactions among RP risk factors and exploit these relationships to enhance both the understanding and prediction of RP. Methods: The authors studied 54 nonsmall-cell lung cancer patients who received curative 3D-conformal radiotherapy. Nineteen RP events were observed (common toxicity criteria for adverse events grade 2 or higher). Serum concentration of the following four candidate biomarkers were measured at baseline and midtreatment: alpha-2-macroglobulin, angiotensin converting enzyme (ACE), transforming growth factor, interleukin-6. Dose-volumetric and clinical parameters were also included as covariates. Feature selection was performed using a Markov blanket approach based on the Koller–Sahami filter. The Markov chain Monte Carlo technique estimated the posterior distribution of BN graphs built from the observed data of the selected variables and causality constraints. RP probability was estimated using a limited number of high posterior graphs (ensemble) and was averaged for the final RP estimate using Bayes’ rule. A resampling method based on bootstrapping was applied to model training and validation in order to control under- and overfit pitfalls. Results: RP prediction power of the BN ensemble approach reached its optimum at a size of 200. The optimized performance of the BN model recorded an area under the receiver operating characteristic curve (AUC) of 0.83, which was significantly higher than multivariate logistic regression (0

  19. ATM Polymorphisms Predict Severe Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Huihua [Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan (China); Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Zhensheng [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Xu, Ting [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Qiming; Liu, Hongliang [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko; Gomez, Daniel [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Li-E [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Qingyi, E-mail: qwei@mdanderson.org [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-03-15

    Purpose: The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP). Methods and Materials: We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered. Results: Of 362 patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ≥3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites. Conclusions: ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.

  20. The TGF-β1 dynamics during radiation therapy and its correlation to symptomatic radiation pneumonitis in lung cancer patients

    Directory of Open Access Journals (Sweden)

    Wang Young-Pil

    2009-01-01

    Full Text Available Abstract Backgroud The underlying molecular and cellular mechanisms of radiation pneumonitis (RP are very complex. Several biological factors need to be considered together with the well known dosimetric parameters for understanding the molecular events in developing RP in lung cancer patients. The aim of this study was to correlate the variations of the cytokine levels in lung cancer patients during radiation therapy (RT with the occurrence of symptomatic RP. Methods Thirty-four lung cancer patients who received three-dimensional conformal radiation therapy were evaluated prospectively. Serial blood samples before, at the beginning, in the middle of, at the end of RT and 2 and 4 weeks after RT were analyzed for IL-1α, IL-6, IL-10, TNF-α and TGF-β1 by performing enzyme-linked immunosorbent assay. The predictive values of dosimetric factors for RP were evaluated, too. Results Overall, 8 patients (23.5% had grade ≥ 2 RP. By serial measurement of cytokines level, only the TGF-β1 level showed a correlation to the symptomatic RP. None of the other cytokines, IL-1α, IL-6, IL-10 and TNF-α level was correlated with the risk of RP. The mean pretreatment TGF-β1 level did not differ between RP and non-RP groups. However, during the period of radiation treatment, the TGF-β1 level began to increase at the end of RT in the RP group and became significantly higher 4 weeks after RT (p = 0.007. Using an ANOVA model for repeated-measures, we found significant associations between the changes of TGF-β1 during the time course of the RT and the risk of developing RP (p < 0.001. Most of the dosimetric factors showed a significant association with RP. Conclusion Our results show that the changes of TGF-β1 could be correlated with RP and the incorporation of the biological parameters into the dosimetric data could be useful for predicting symptomatic RP.

  1. Enalapril mitigates radiation-induced pneumonitis and pulmonary fibrosis if started 35 days after whole-thorax irradiation.

    Science.gov (United States)

    Gao, Feng; Fish, Brian L; Moulder, John E; Jacobs, Elizabeth R; Medhora, Meetha

    2013-11-01

    Victims of a radiological attack or nuclear accident may receive high-dose, heterogeneous exposures from radiation to the chest that lead to lung damage. Our goal is to develop countermeasures to mitigate such injuries. We used WAG/RijCmcr rats receiving 13 Gy to the whole thorax to induce pulmonary fibrosis within 210 days. The angiotensin converting enzyme (ACE) inhibitor enalapril was evaluated as a mitigator of these injuries at two doses (18 and 36 mg/m(2)/day) and 8 schedules: starting at 7, 35, 70, 105 and 140 days and continuing to 210 days or starting at 7 days and stopping at 30, 60 or 90 days after whole-thorax irradiation. The earliest start date at 7 days after irradiation would provide an adequate window of time for triage and dosimetry. Survival after 35 days, as permitted by our Institutional Animal Care and Use Committee (IACUC) was also recorded as a primary end point of pneumonitis. Pulmonary fibrosis was evaluated using the Sircol biochemical assay to measure lung collagen. Our results indicated that a short course of either dose of enalapril from 7-90 days improved survival. However, pulmonary fibrosis was only mitigated by the higher dose of enalapril (36 mg/m(2)/day). The latest effective start date for the drug was 35 days after irradiation. These results indicate that ACE inhibitors can be started at least a month after irradiation for mitigation of pneumonitis and/or pulmonary fibrosis.

  2. Role of lysosomal enzymes released by alveolar macrophages in the pathogenesis of the acute phase of hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    J. L. Pérez-Arellano

    1995-01-01

    Full Text Available Hydrolytic enzymes are the major constituents of alveolar macrophages (AM and have been shown to be involved in many aspects of the inflammatory pulmonary response. The aim of this study was to evaluate the role of lysosomal enzymes in the acute phase of hypersensitivity pneumonitis (HPs. An experimental study on AM lysosomal enzymes of an HP-guinea-pig model was performed. The results obtained both in vivo and in vitro suggest that intracellular enzymatic activity decrease is, at least partly, due to release of lysosomal enzymes into the medium. A positive but slight correlation was found between extracellular lysosomal activity and four parameters of lung lesion (lung index, bronchoalveolar fluid total (BALF protein concentration, BALF LDH and BALF alkaline phosphatase activities. All the above findings suggest that the AM release of lysosomal enzymes during HP is a factor involved, although possibly not the only one, in the pulmonary lesions appearing in this disease.

  3. Association Between White Blood Cell Count Following Radiation Therapy With Radiation Pneumonitis in Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chad; Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Hongmei [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou (China); Levy, Lawrence B. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang, Yan [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Xu, Ting; Nguyen, Quynh; Komaki, Ritsuko [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-02-01

    Purpose: Radiation pneumonitis (RP) is an inflammatory response to radiation therapy (RT). We assessed the association between RP and white blood cell (WBC) count, an established metric of systemic inflammation, after RT for non-small cell lung cancer. Methods and Materials: We retrospectively analyzed 366 patients with non-small cell lung cancer who received ≥60 Gy as definitive therapy. The primary endpoint was whether WBC count after RT (defined as 2 weeks through 3 months after RT completion) was associated with grade ≥3 or grade ≥2 RP. Median lung volume receiving ≥20 Gy (V{sub 20}) was 31%, and post-RT WBC counts ranged from 1.7 to 21.2 × 10{sup 3} WBCs/μL. Odds ratios (ORs) associating clinical variables and post-RT WBC counts with RP were calculated via logistic regression. A recursive-partitioning algorithm was used to define optimal post-RT WBC count cut points. Results: Post-RT WBC counts were significantly higher in patients with grade ≥3 RP than without (P<.05). Optimal cut points for post-RT WBC count were found to be 7.4 and 8.0 × 10{sup 3}/μL for grade ≥3 and ≥2 RP, respectively. Univariate analysis revealed significant associations between post-RT WBC count and grade ≥3 (n=46, OR=2.6, 95% confidence interval [CI] 1.4‒4.9, P=.003) and grade ≥2 RP (n=164, OR=2.0, 95% CI 1.2‒3.4, P=.01). This association held in a stepwise multivariate regression. Of note, V{sub 20} was found to be significantly associated with grade ≥2 RP (OR=2.2, 95% CI 1.2‒3.4, P=.01) and trended toward significance for grade ≥3 RP (OR=1.9, 95% CI 1.0-3.5, P=.06). Conclusions: Post-RT WBC counts were significantly and independently associated with RP and have potential utility as a diagnostic or predictive marker for this toxicity.

  4. Severe acute radiation pneumonitis after concurrent chemoradiotherapy in non-small cell lung cancer%非小细胞肺癌同期放化疗后重度急性放射性肺炎的预测因素

    Institute of Scientific and Technical Information of China (English)

    王谨; 邓小武; 陈明; 庄婷婷; 何智纯; 彭芳; 马红莲; 周琦超; 张黎; 何振宇; 包勇

    2012-01-01

    Objective The study is to investigate the predictive values of dosimetric parameters and patient related factors in severe acute radiation pneumonitis (SARP) after concurrent chemoradiotherapy in non-small cell lung cancer (NSCLC).Methods In all,147 NSCLC patients treated with concurrent chemotherapy and 3DCRT between 2006 and 2010 was collected.Independent sample t test was used to compare parameter values between patients with SARP and those without SARP.Logistic regression was used to identify significant determined factor.Predictive value of each parameter was tested by ROC analysis.Pearson correlation was used to analyze correlations between parameters.Represent factors were identified by factor analysis.Results The incidence of SARP was 9.5% ( 14/147 ).The means lung dose (MLD),V20,V30,V40,and V50 ( x2 =4.87 -6.84,P =0.009 -0.025,respectively ) were determining factors for SARP.Our datasets shows that for SARP <5%,MLD,V20,V30,V40 and V50 should be ≤16.77 Gy,V20≤34.15%,.V30 ≤23.62%,.V40 ≤ 18.57%,V50 ≤ 13.02%.ROC analysis show that areas under MLD,V20,V30,V40 and V50 curves was corresponding to 0.678,0.661,0.667,0.677,and 0.651,respectively.In addition,the sensitivity and specificity of each parameter at cutoff values are:78.0% and 48.1% for MLD;42.9% and 82.0% for V2o ;78.6% and 52.9% for V30 ;71.4% and 61.7% for V40,and 57.1% and 67.7% for V50.Factor analysis suggest that we can choose 1 or 2 parameters from MLD,V20,or V30,and another from V40 or V50 for predicting.The incidence of SARP was greater in patients with tumorsin right lower lung than other locations ( 22.2% vs 6.7%,x2 =6.19,P =0.0 2 3 ).Conclusions The MLD,V20,V30,V40 and V50 are determining factors for SARP.As predictive value of each parameter alone is relatively week,using two or more parameters to predict SARP is recommended.%目的 评价剂量体积直方图参数及临床因素对非细胞肺癌三维适形放疗同期化疗

  5. Mesalizine-Induced Acute Pancreatitis and Interstitial Pneumonitis in a Patient with Ulcerative Colitis.

    Science.gov (United States)

    Chung, Min Jae; Lee, Jae Hee; Moon, Kyung Rye

    2015-12-01

    Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease. Mesalizine for the first-line therapy of UC has adverse effects include pancreatitis, pneumonia and pericarditis. UC complicated by two coexisting conditions, however, is very rare. Moreover, drug-related pulmonary toxicity is particularly rare. An 11-year-old male patient was hospitalized for recurring upper abdominal pain after meals with vomiting, hematochezia and exertional dyspnea developing at 2 weeks of mesalizine therapy for UC. The serum level of lipase was elevated. Chest X-ray and thorax computed tomography showed interstitial pneumonitis. Mesalizine was discontinued and steroid therapy was initiated. Five days after admission, symptoms were resolved and mesalizine was resumed after a drop in amylase and lipase level. Symptoms returned the following day, however, accompanied by increased the serum levels of amylase and lipase. Mesalizine was discontinued again and recurring symptoms rapidly improved.

  6. Airbag Pneumonitis

    Directory of Open Access Journals (Sweden)

    Raghav Govindarajan

    2010-01-01

    Full Text Available The widespread and mandatory use of airbags has resulted in various patterns of injuries and complications unique to their use. Airbags have been implicated in a spectrum of pulmonary conditions ranging from exacerbation of asthma, reactive airway diseases to new onset asthma. We report a case of inhalational chemical pneumonitis that developed after exposure to the airbag fumes.

  7. Histomorphologic change of radiation pneumonitis in rat lungs: captopril reduces rat lung injury induced by irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Hee [College of Medicine, Keimhyung Univ., Taegu (Korea, Republic of)

    1999-09-01

    To assess the histomorphologic changes in the rat lung injury induced by radiation, to determine whether captopril reduces the rat lung injury and to evaluate change in TNF-{alpha} and TGF {beta} and rat lung damage by radiation and captopril. Right lungs in male Sprague-Dawley rats were divided irradiation alone (10, 20, 30 Gy) or radiation (same dose with radiation alone group) with captopril (500 mg/L). Radiation alone group were sacrificed at twelve hours and eleven weeks after radiation and radiation with captopril group (captopril group) were sacrificed at eleven weeks after radiation with captopril. We examined the light microscope and electron microscopic features in the groups. In radiation alone group, there were patch parenchymal collapse and consolidation at twelve hours after radiation. The increase of radiation dose shows more prominent the severity and broader the affected areas. Eleven weeks after radiation, the severity and areas of fibrosis had increased in proportion to radiation dose given in the radiation alone group. There was notable decrease of lung fibrosis in captopril group than in radiation alone group. The number of mast cells rapidly increased with increase of radiation dose in radiation alone group and the degree of increase of mast cell number and severity of collagen accumulation more decreased in captopril group than in radiation alone group. In radiation alone group expression of TNF-{alpha} and TGF-{beta}] increased according to increase of radiation dose at twelve hours after radiation in both group. At eleven weeks after radiation, expression of TGF- P increased according to increase of radiation dose in radiation group but somewhat decreased in captopril group. In the captopril group the collagen deposition increased but less dense than those of radiation alone group. The severity of perivascular thickening, capillary change, the number and degranulation of mast cells more decreased in the captopril group than in the radiation

  8. Bacteriotherapy of acute radiation sickness

    Energy Technology Data Exchange (ETDEWEB)

    Mal' tsev, V.N.; Korshunov, V.M.; Strel' nikov, V.A.; Ikonnikova, T.B.; Kissina, E.V.; Lyannaya, A.M.; Goncharova, G.I.; Pinegin, B.V.

    1979-04-01

    Acute sickness is associated with intestinal dysbacteriosis; there is a radical decrease in number of microorganisms of lactic fermentation (bifidobacterium, lactobacillus) and an increase in E. coli proteus, enterococcus, and clostridium. Extensive use is made of live microorganisms in the treatment of various diseases associated with intestinal dysbacteriosis; in the case of acute radiation sickness, yeast, colibacterin, and E. coli have been used. In a number of cases, such therapy increased survival and life expectancy of irradiated animals. In this study, microorganisms of lactic fermentation (lactobacillus, bifidobacterium) and colibacterin were used for treatment of acute radiation sickness.

  9. Chronic hypersensitivity pneumonitis

    Science.gov (United States)

    Pereira, Carlos AC; Gimenez, Andréa; Kuranishi, Lilian; Storrer, Karin

    2016-01-01

    Hypersensitivity pneumonitis (HSP) is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary. PMID:27703382

  10. Fatal measles pneumonitis during Hodgkin's lymphoma.

    Science.gov (United States)

    Wyplosz, Benjamin; Lafarge, Marion; Escaut, Lélia; Stern, Jean-Baptiste

    2013-10-08

    The treatment of measles pneumonitis in immunocompromised adults is not established. We describe a patient with Hodgkin's lymphoma who developed acute pneumonia during a measles infection. On day 13, intravenous ribavirin and immunoglobulins were administrated. On day 18, the patient developed acute respiratory failure. An examination of transbronchial pulmonary biopsies showed Warthin-Finkeldey giant cells that are pathognomonic of measles pneumonitis. The patient died despite aggressive supportive care. Our case and a review of literature show that measles pneumonitis is routinely fatal in patients with cancer. We suggest that antiviral drugs should be considered as soon as the diagnosis has been established.

  11. Predictive factors of symptomatic radiation pneumonitis in primary and metastatic lung tumors treated with stereotactic ablative body radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kang Pyo; Lee, Jeong Shim; Cho, Yeona; Chung, Seung Yeun; Lee, Jason Joon Bock; Lee, Chang Geol; Cho, Jae Ho [Dept. of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2017-06-15

    Although stereotactic ablative body radiotherapy (SABR) is widely used therapeutic technique, predictive factors of radiation pneumonitis (RP) after SABR remain undefined. We aimed to investigate the predictive factors affecting RP in patients with primary or metastatic lung tumors who received SABR. From 2012 to 2015, we reviewed 59 patients with 72 primary or metastatic lung tumors treated with SABR, and performed analyses of clinical and dosimetric variables related to symptomatic RP. SABR was delivered as 45–60 Gy in 3–4 fractions, which were over 100 Gy in BED when the α/β value was assumed to be 10. Tumor volume and other various dose volume factors were analyzed using median value as a cutoff value. RP was graded per the Common Terminology Criteria for Adverse Events v4.03. At the median follow-up period of 11 months, symptomatic RP was observed in 13 lesions (12 patients, 18.1%), including grade 2 RP in 11 lesions and grade 3 in 2 lesions. Patients with planning target volume (PTV) of ≤14.35 mL had significantly lower rates of symptomatic RP when compared to others (8.6% vs. 27%; p = 0.048). Rates of symptomatic RP in patients with internal gross tumor volume (iGTV) >4.21 mL were higher than with ≤4.21 mL (29.7% vs. 6.1%; p = 0.017). The incidence of symptomatic RP following treatment with SABR was acceptable with grade 2 RP being observed in most patients. iGTV over 4.21 mL and PTV of over 14.35 mL were significant predictive factors related to symptomatic RP.

  12. Acute necrotising pneumonitis associated with Suttonella ornithocola infection in tits (Paridae).

    Science.gov (United States)

    Lawson, Becki; Malnick, Henry; Pennycott, Tom W; Macgregor, Shaheed K; John, Shinto K; Duncan, Gwen; Hughes, Laura A; Chantrey, Julian; Cunningham, Andrew A

    2011-04-01

    Suttonella ornithocola, first isolated from the lungs of British tit species in 1996, was found to be a novel bacterium belonging to the family Cardiobacteriaceae. Comprehensive surveillance of garden bird mortality across Great Britain between April 2005 and April 2009 involved post mortem and microbiological examination of 82 tits (Paridae; multiple species) and six long-tailed tits (Aegithalidae; Aegithalos caudatus). S. ornithocola was isolated from six birds submitted from six incidents of morbidity and mortality involving Paridae and Aegithalidae species with a wide geographical distribution. The mortality incidents occurred sporadically at low incidence throughout the study period, which suggested that the infection is endemic in native bird populations, with a seasonal peak during early spring. Histopathological examination showed multiple foci of acute pulmonary necrosis associated with gram-negative cocco-bacillary bacteria. These findings supported the hypothesis that S. ornithocola is a primary pathogen of tits in Great Britain.

  13. Effects of Salviae Miltiorrhizae Liguspyragine Hydrochloride and Glucose Injection on the prevention and treatment of acute radiation-induced pneumonitis in rats%参芎注射液防治胸部肿瘤放疗导致放射性肺损伤的实验研究

    Institute of Scientific and Technical Information of China (English)

    周晓红; 唐力; 齐亚灵

    2014-01-01

    necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) levels in plasma of rats were higher than those in the other groups. In the group with irradiation and medicine treatment, the TNF-αand TGF-βlevels in plasma were higher than those in the normal control group and single medicine treatment group. In the group with single irradiation for four weeks,some petechial hemorrhages on the surface of the lung were visible to the naked eye. In the groups with medicine treatment, the petechi-al hemorrhages on the surface of the lung visibly reduced. According to the pathological mechanism of lung tissues, the groups with Sal-viae Miltiorrhizae Liguspyragine Hydrochloride and Glucose Injection exhibited less inflammation than the single irradiation group. Ir-radiation at 20 Gy for four weeks followed by a daily abdominal injection was slightly better than single irradiation, but the effects were not obvious. Conclusion: Salviae Miltiorrhizae Liguspyragine Hydrochloride and Glucose Injection could prevent the occurrence of lung injury by reducing the TNF-αand TGF-βlevels in plasma. After the occurrence of radiation-induced pneumonitis, the application of medicine could not decrease the symptoms.%目的:放射性肺损伤是影响胸部肿瘤放射治疗的最重要因素之一,以明确参芎注射液对放射性肺损伤是否预防及治疗作用,并初步探讨其作用机制。方法:选取体重200±14g成年雄性大鼠105只,分为7组,即正常对照组(N),单独给药组(D),单独照射组(Z),照射10 Gy+给药组(Z10),照射15 Gy+给药组(Z15),照射20 Gy+晚期给药组(照射后4周给药,Z20a),照射20 Gy+早期给药组(照射同时给药,Z20b)。所有药物均经腹腔注射。分别于照射后2、4、6、8、10 W处死大鼠,取血清,应用ELISA法检测TNF-α和TGF-β1,取肺组织制成石蜡切片,HE染色观察病理变化。结果:单纯照射组血清TNF-α和TGF-β1值

  14. Acute radiation syndrome and chronic radiation syndrome.

    Science.gov (United States)

    Grammaticos, Philip; Giannoula, Evanthia; Fountos, George P

    2013-01-01

    Acute radiation syndrome (ARS) or sickness or poisoning or toxicity is induced after a whole body exposure of men to high doses of radiation between 1-12Gy. First symptoms are from the gastrointestinal system, which together with bone marrow are the most sensitive parts of our body. Chronic radiation syndrome (CRS) may be induced by smaller than 1Gy radiation doses or after a mild form of ARS. Prophylaxis and treatment suggestions are described. In cases of ARS, a large part of the exposed population after proper medical care may survive, while without medical care this part of the population will be lost. Prophylaxis may also save another part of the population.

  15. SU-D-16A-03: A Radiation Pneumonitis Dose-Response Model Incorporating Non- Local Radiation-Induced Bystander Effect

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, J; Snyder, K; Zhong, H; Chetty, I [Henry Ford Health System, Dept. Radiation Oncology, Detroit, MI (United States)

    2014-06-01

    Purpose: Dose-response models that can reliably predict radiation pneumonitis (RP) to guide radiation therapy (RT) for lung cancer presently do not exist. A model is proposed that incorporates non-local radiationinduced bystander effect (RIBE). Methods: A single sigmoid response function, derived from published data for whole lung irradiation, relates RP probability to cumulative lung damage, regardless of fractionation scheme. Lung damage is assumed to be caused by direct local radiation damage, quantified via the linear-quadratic (LQ) model, and RIBE. Based on published data, RIBE is assumed to be activated when per-fraction dose rises above ∼0.6 Gy, but is constant with dose above that threshold. Integral RIBE damage is assumed proportional to lung volume irradiated above ∼0.6 Gy per fraction. Key model parameters include LQ α and β, and two RIBE parameters: the single-fraction probability δ of damage, and a proportionality parameter κ that relates the potential for RIBE damage to irradiated lung volume. All parameters are tentatively fitted from published data, the RIBE parameters from published RP rates for conventionally fractionated RT (CFRT) and stereotactic body RT (SBRT). Results: The model predicts dose-response curves that are consistent with clinical experience. It provides a tentative explanation for why V20 (33 fractions), V13 (20 fractions) and V5 (<10 fractions) are observed to be correlated with RP. It also provides a plausible explanation for the success of SBRT — RIBE damage increases with the number of fractions, so penalizes CFRT relative to SBRT. Conclusion: The proposed model is relatively simple, extrapolates from published data, plausibly explains several clinical observations, and produces dose-response curves that are consistent with clinical experience. While capable of elaboration, its ability to explain doseresponse experience with different fractionation schemes using a small number of assumptions and parameters is an

  16. Genetic variants in PI3K/AKT pathway are associated with severe radiation pneumonitis in lung cancer patients treated with radiation therapy.

    Science.gov (United States)

    Tang, Yang; Liu, Bo; Li, Jing; Wu, Huanlei; Yang, Ju; Zhou, Xiao; Yi, Mingxiao; Li, Qianxia; Yu, Shiying; Yuan, Xianglin

    2016-01-01

    PI3K/AKT pathway plays important roles in inflammatory and fibrotic diseases while its connection to radiation pneumonitis (RP) is unclear. In this study, we explored the associations of genetic variants in PI3K/AKT pathway with RP in lung cancer patients with radiotherapy. Two hundred and sixty one lung cancer patients with radiotherapy were included in this prospective study (NCT02490319) and genotyped by MassArray and Sanger Sequence methods. By multivariate Cox hazard analysis and multiple testing, GA/GG genotype of AKT2: rs33933140 (HR = 0.272, 95% CI: 0.140-0.530, P = 1.3E-4, Pc = 9.1E-4), and the GT/GG genotype of PI3CA: rs9838117 (HR = 0.132, 95% CI: 0.042-0.416, P = 0.001, Pc = 0.006) were found to be strongly associated with a decreased occurrence of RP ≥ grade 3. And patients with the CT/TT genotype of AKT2: rs11880261 had a notably higher incidence of RP ≥ grade 3 (HR = 2.950, 95% CI: 1.380-6.305, P = 0.005, Pc = 0.025). We concluded that the genetic variants of PI3K/AKT pathway were significantly related to RP of grade ≥ 3 and may thus be predictors of severe RP before radiotherapy, if further validated in larger population.

  17. Change in Diffusing Capacity After Radiation as an Objective Measure for Grading Radiation Pneumonitis in Patients Treated for Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Guerra, Jose Luis [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Department of Radiation Oncology, Hospitales Universitarios Virgen del Rocio, Seville (Spain); Gomez, Daniel, E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Zhuang Yan; Levy, Lawrence B. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Eapen, George [Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Liu Hongmei; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-08-01

    Purpose: Scoring of radiation pneumonitis (RP), a dose-limiting toxicity after thoracic radiochemotherapy, is subjective and thus inconsistent among studies. Here we investigated whether the extent of change in diffusing capacity of the lung for carbon monoxide (DLCO) after radiation therapy (RT) for non-small-cell lung cancer (NSCLC) could be used as an objective means of quantifying RP. Patients and Methods: We analyzed potential correlations between DLCO and RP in 140 patients who received definitive RT ({>=}60 Gy) with or without chemotherapy for primary NSCLC. All underwent DLCO analysis before and after RT. Post-RT DLCO values within 1 week of the RP diagnosis (Grade 0, 1, 2, or 3) were selected and compared with that individual's preradiation values. Percent reductions in DLCO and RP grade were compared by point biserial correlation in the entire patient group and in subgroups stratified according to various clinical factors. Results: Patients experiencing Grade 0, 1, 2, or 3 RP had median percentage changes in DLCO after RT of 10.7%, 13%, 22.1%, or 35.2%. Percent reduction in DLCO correlated with RP Grade {<=}1 vs. {>=}2 (p = 0.0004). This association held for the following subgroups: age {>=}65 years, advanced stage, smokers, use of chemotherapy, volume of normal lung receiving at least 20 Gy {>=}30%, and baseline DLCO or forced expiratory volume in 1 second {>=}60%. Conclusions: By correlating percent change in DLCO from pretreatment values at the time of diagnosis of RP with RP grade, we were able to identify categories of RP based on the change in DLCO. These criteria provide a basis for an objective scoring system for RP based on change in DLCO.

  18. Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.

    Science.gov (United States)

    Wen, Juyi; Liu, Hongliang; Wang, Qiming; Liu, Zhensheng; Li, Yangkai; Xiong, Huihua; Xu, Ting; Li, Peng; Wang, Li-E; Gomez, Daniel R; Mohan, Radhe; Komaki, Ritsuko; Liao, Zhongxing; Wei, Qingyi

    2014-07-01

    LIN28 is an RNA-binding protein that not only plays key roles in multiple cellular developmental processes and tumourigenesis, but also is involved in tissue inflammatory response. However, no published study has investigated associations between genetic variants in LIN28 and radiation-induced pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of LIN28A (rs11247946 T>C, rs3811464 C>T, rs11581746 T>C, and rs12728900 G>A) and LIN28B (rs314280 G>A, rs12194974 G>A, rs17065417 A>C and rs314276 C>A) in 362 patients with NSCLC, who received definitive radio(chemo)therapy. The associations between RP risk and genotypes were assessed by hazards ratio (HR) in Cox proportional hazards regression analysis with time to event considered with and without adjustment for potential confounders. Multivariate analyses found that patients carrying LIN28B rs314280 AG and AA/AG or rs314276 AC and AA/AC genotypes had a higher risk of grade ⩾3 RP (for rs314280 AG and AA/AG versus GG, adjusted HR=2.97 and 2.23, 95% confidence interval (CI)=1.32-6.72 and 1.01-4.94, P=0.009 and 0.048, respectively; for rs314276 AC and AA/AC versus CC, adjusted HR=2.30 and 2.00, 95% CI=1.24-4.28 and 1.11-3.62, and P=0.008 and 0.022, respectively). Further stratified analyses showed a more consistent and profound risk in the subgroups of age LIN28A, may be biomarkers for susceptibility to severe RP in NSCLC patients. Large, prospective studies are needed to confirm our findings. Copyright © 2014. Published by Elsevier Ltd.

  19. Chronic hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    Pereira CA

    2016-09-01

    Full Text Available Carlos AC Pereira,1 Andréa Gimenez,2 Lilian Kuranishi,2 Karin Storrer 2 1Interstitial Lung Diseases Program, 2Pulmonology Postgraduate, Federal University of São Paulo, São Paulo, Brazil Abstract: Hypersensitivity pneumonitis (HSP is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary. Keywords: interstitial lung diseases, extrinsic allergic alveolitis, diffuse lung disease, lung immune response, HRCT, farmers lung

  20. Lung Texture in Serial Thoracic Computed Tomography Scans: Correlation of Radiomics-based Features With Radiation Therapy Dose and Radiation Pneumonitis Development

    Energy Technology Data Exchange (ETDEWEB)

    Cunliffe, Alexandra; Armato, Samuel G. [Department of Radiology, The University of Chicago, Chicago, Illinois (United States); Castillo, Richard [Department of Radiation Oncology, The University of Texas Medical Branch, Galveston, Texas (United States); Pham, Ngoc [Baylor College of Medicine, Houston, Texas (United States); Guerrero, Thomas [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Al-Hallaq, Hania A., E-mail: hal-hallaq@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois (United States)

    2015-04-01

    Purpose: To assess the relationship between radiation dose and change in a set of mathematical intensity- and texture-based features and to determine the ability of texture analysis to identify patients who develop radiation pneumonitis (RP). Methods and Materials: A total of 106 patients who received radiation therapy (RT) for esophageal cancer were retrospectively identified under institutional review board approval. For each patient, diagnostic computed tomography (CT) scans were acquired before (0-168 days) and after (5-120 days) RT, and a treatment planning CT scan with an associated dose map was obtained. 32- × 32-pixel regions of interest (ROIs) were randomly identified in the lungs of each pre-RT scan. ROIs were subsequently mapped to the post-RT scan and the planning scan dose map by using deformable image registration. The changes in 20 feature values (ΔFV) between pre- and post-RT scan ROIs were calculated. Regression modeling and analysis of variance were used to test the relationships between ΔFV, mean ROI dose, and development of grade ≥2 RP. Area under the receiver operating characteristic curve (AUC) was calculated to determine each feature's ability to distinguish between patients with and those without RP. A classifier was constructed to determine whether 2- or 3-feature combinations could improve RP distinction. Results: For all 20 features, a significant ΔFV was observed with increasing radiation dose. Twelve features changed significantly for patients with RP. Individual texture features could discriminate between patients with and those without RP with moderate performance (AUCs from 0.49 to 0.78). Using multiple features in a classifier, AUC increased significantly (0.59-0.84). Conclusions: A relationship between dose and change in a set of image-based features was observed. For 12 features, ΔFV was significantly related to RP development. This study demonstrated the ability of radiomics to provide a quantitative, individualized

  1. Radiation Pneumonitis in Association with Internal Mammary Node Irradiation in Breast Cancer Patients: An Ancillary Result from the KROG 08-06 Study

    Science.gov (United States)

    Choi, Jinhyun; Kim, Yong Bae; Shin, Kyung Hwan; Ahn, Sung-Ja; Lee, Hyung-Sik; Park, Won; Kim, Su Ssan; Kim, Jin Hee; Lee, Kyu Chan; Kim, Dong Won; Suh, Hyun Suk; Park, Kyung Ran; Shin, Hyun Soo

    2016-01-01

    Purpose The aim of this study is to present the incidence of radiation pneumonitis (RP) reported within 6 months after treatment for breast cancer with or without internal mammary node irradiation (IMNI). Methods In the Korean Radiation Oncology Group (KROG) 08-06 phase III randomized trial, patients who were node-positive after surgery were randomly assigned to receive radiotherapy either with or without IMNI. A total of 747 patients were enrolled, and three-dimensional treatment planning with computed tomography simulation was performed for all patients. Of the 747 patients, 722 underwent chest X-rays before and within 6 months after radiotherapy. These 722 patients underwent evaluation, and RP was diagnosed on the basis of chest radiography findings and clinical symptoms. The relationship between the incidence of RP and clinical/dosimetric parameters was analyzed. Results RP developed in 35 patients (4.8%), including grade 1 RP in 26 patients (3.6%), grade 2 RP in nine patients (1.2%); there was no incidence of grade 3 or higher RP. Grade 2 RP cases were observed in only the IMNI group. The risk of developing RP was influenced by IMNI treatment; pneumonitis occurred in 6.5% of patients (n=23/356) who underwent IMNI and in 3.3% of patients (n=12/366) who did not (p=0.047). The differences in lung dosimetric parameters (mean lung dose, V10–40) were statistically significant between the two groups. Conclusion IMNI treatment resulted in increased radiation exposure to the lung and a higher rate of RP, but the incidence and severity of RP was minimal and acceptable. This minor impact on morbidity should be balanced with the impact on survival outcome in future analyses. PMID:27721877

  2. [Recurrence of the acute respiratory distress syndrome (ARDS) in a patient with Sai-rei-to-induced pneumonitis].

    Science.gov (United States)

    Narita, Yusuke; Yamaguchi, Tetsuo; Tanaka, Kensuke; Urushiyama, Hirokazu; Togashi, Yuki; Zaima, Mika; Kohno, Chiyoko; Yamada, Yoshihito

    2008-10-01

    An 83-year-old woman was admitted to our hospital because of fever and difficulty in walking with marked hypoxemia and diffuse ground glass opacities in bilateral lung fields by chest radiography and CT scanning. Treatment with antibiotics and corticosteroids resulted in improvement of the clinical findings and successful weaning from mechanical ventilation. At first, we diagnosed severe mycoplasma pneumonia because of a 2560 titer in a particle agglutiation (PA) test. Five days after discharge, she was given a second emergency admission, because of fever and difficulty in walking. Chest X-ray film revealed improvement after administration of methylprednisolone. Her detailed medical history proved that she had been treated with a Chinese herbal drug, Sai-rei-to, for several weeks before first admission. We finally diagnosed her disease as Sai-rei-to-induced pneumonitis. Despite intensive treatment, she finally died. The histopathological findings (H-E stain) of the autopsied lungs showed hyaline membrane formation and hyperplasia of type II alveolar epithelium cells, so-called, diffuse alveolar damage. This case and other referred in the literature suggest that Sai-rei-to-induced pneumonitis can become severe.

  3. Radiation Pneumonitis After Stereotactic Body Radiation Therapy for Early Stage Non-small Cell Lung Cancer%早期非小细胞肺癌立体定向放射治疗后的放射性肺炎

    Institute of Scientific and Technical Information of China (English)

    陈露; 赵娅琴; 许峰

    2014-01-01

    With the development of radiation technology, stereotactic body radiation therapy (SBRT) has been widely used in early stage non-small cell lung cancer (NSCLC). It is not only the standard therapy for medically inoperable early-stage NSCLC, but also one of the therapies for operable early-stage NSCLC. Radiation pneumonitis (RP) is one of the most common adverse effects atfer SBRT, it may reduce the patients’ quality of life, even cause treatment failure. hTerefore, in order to improve the patients’ quality of life and enhance local control rate of tumor, it is important to reduce the risk of RP. hTe unique fractionation schemes and the dose distribution of SBRT make it not only different from conventional fraction radiation therapy in treatment outcomes, but also in the incidence of radiation pneumonitis. hTis article reviews the applying of SBRT for early stage NSCLC, the incidence of radiation pneumonitis, radiological appearance atfer SBRT and predictive factors.%随着放疗技术的进步,立体定向放射治疗(stereotactic body radiation therapy, SBRT)在早期非小细胞肺癌(non-small cell lung cancer, NSCLC)中得到了广泛应用,其不仅是不可手术的早期NSCLC的标准治疗方法,也是可手术的早期NSCLC的治疗方法之一。放射性肺炎(radiation pneumonitis, RP)是SBRT治疗后最常见的并发症。SBRT独特的分割计划和剂量分布使其不仅在治疗效果上和常规分割放疗不同,而且治疗后引起的RP和常规分割放疗引起的RP也有所不同。RP的发生可降低患者的生活质量,甚至导致治疗失败。因此,降低RP的风险对提高患者的生活质量和肿瘤的控制率有重要意义。本文就SBRT在早期NSCLC治疗中应用、治疗后RP的发生率、影像学表现以及预测因素方面作一综述。

  4. 二丁酰环磷腺苷钙治疗放射性肺炎的临床观察%Clinical observation of DBC AMP-Ca in the treatment of radiation pneumonitis

    Institute of Scientific and Technical Information of China (English)

    朱巍; 郝志强

    2015-01-01

    目的观察二丁酰环磷腺苷钙综合治疗放射性肺炎的临床疗效。方法选取肺癌放疗后引起放射性肺炎2、3、4级患者30例,随机分为观察组和对照组。对照组予吸氧、糖皮质激素、祛痰、抗氧自由基及抗生素治疗,3级以上加用氨茶碱治疗。治疗组在对照组的基础上加用二丁酰环磷腺苷钙静滴,两周后评价近期疗效。结果治疗组有效率优于对照组(P<0.05)。结论二丁酰环磷腺苷钙综合治疗肺癌放疗后放射性肺炎有效。%Objective To observe the clinical efifcacy of DBC AMP-Ca in the treatment of radiation pneumonitis. Methods 30 patients with lung cancer, complicating 2, 3 and 4 degree of radiation pneumonitis were randomly divided into treatment group and control group. Patient in control group were given oxygenaton, glucocorticoid, expectorant, clearing oxygen free radical and antibiotic treatment, while those with more than 3 degree of radiation pneumonitis aminophylline was used. Patients in treatment group received DBC AMP-Ca intravenously based on the treatment of control group. The effects were compared after two weeks. Results The efficiency of DBC AMP-Ca in treatment of radiation pneumonitis is superior to that of control group (P<0.05). Conclusions DBC AMP-Ca is effective for radiation pneumonitis in patients with lung cancer caused by radiotherapy.

  5. Effect of diabetes mellitus on the development of radiation pneumonitis in patients with non-small cell lung cancer%糖尿病与放射性肺炎发生的相关危险性分析

    Institute of Scientific and Technical Information of China (English)

    宋浩; 于金明

    2009-01-01

    Objective The purpose of this study was to investigate whether the associated diabetes mellitus exerts a certain effect on the development of radiation pneumonitis in patients with non-small cell lung cancer. Methods 156 patients with non small cell lung cancer were treated with three-dimensional conformal radiation therapy in this study, including 52 associated with diabetes and 104 non-diabetic patients as a control group. All the patients were followed up for one year and the development of radiation pneumonitis was observed. Radiation pneumonitis was diagnosed according to the criteria of radiation therapy oncology group. The morbidities of radiation pneumonitis in the two groups were compared. The relationships between the morbidity of radiation pneumonitis and blood sugar level as well as diabetic history were analyzed by chi-square test. Results Twenty-one (40.4%) of 52 patients with diabetes had radiation pneumonitis (grade 2 or greater), while in the control group only 22 of 104 patients (21.2%) suffered from radiation pneumonitis. There was a statistically significant difference between the two groups in the morbidity of the radiation pneumonitis (P<0.05), with a relative risk value of 2.05 (95% CI, 1.17, 3.58). The rate of the radiation pneumonitis in the patients with a lower blood sugar level (<7 mmol/L) was significantly lower than that in those with a higher blood sugar level (30.6% vs. 62.5%, P<0.05). However, the rate of radiation pneumonitis in the patients with a longer diabetic history was not significantly different from that in those with a shorter diabetic history (P0.05). Conclusion Non-small cell lung cancer patients with diabetes mellitus are more vulnerable than those without to radiation pneumonitis. Therefore, diabetes mellitus is a newly discovered risk factor to radiation pneumonitis, and the blood sugar level is positively correlated with the morbidity of radiation pneumonitis.%目的 探讨伴有糖尿病的肺癌患者在接受放

  6. Instantaneous responses to high-frequency chest wall oscillation in patients with acute pneumonic respiratory failure receiving mechanical ventilation

    Science.gov (United States)

    Chuang, Ming-Lung; Chou, Yi-Ling; Lee, Chai-Yuan; Huang, Shih-Feng

    2017-01-01

    Abstract Background: Endotracheal intubation and prolonged immobilization of patients receiving mechanical ventilation may reduce expectoration function. High-frequency chest wall oscillation (HFCWO) may ameliorate airway secretion movement; however, the instantaneous changes in patients’ cardiopulmonary responses are unknown. Moreover, HFCWO may influence ventilator settings by the vigorous oscillation. The aim of this study was to investigate these issues. Methods: Seventy-three patients (52 men) aged 71.5 ± 13.4 years who were intubated with mechanical ventilation for pneumonic respiratory failure were recruited and randomly classified into 2 groups (HFCWO group, n = 36; and control group who received conventional chest physical therapy (CCPT, n = 37). HFCWO was applied with a fixed protocol, whereas CCPT was conducted using standard protocols. Both groups received sputum suction after the procedure. Changes in ventilator settings and the subjects’ responses were measured at preset intervals and compared within groups and between groups. Results: Oscillation did not affect the ventilator settings (all P > 0.05). The mean airway pressure, breathing frequency, and rapid shallow breathing index increased, and the tidal volume and SpO2 decreased (all P < 0.05). After sputum suction, the peak airway pressure (Ppeak) and minute ventilation decreased (all P < 0.05). The HFCWO group had a lower tidal volume and SpO2 at the end of oscillation, and lower Ppeak and tidal volume after sputum suction than the CCPT group. Conclusions: HFCWO affects breathing pattern and SpO2 but not ventilator settings, whereas CCPT maintains a steadier condition. After sputum suction, HFCWO slightly improved Ppeak compared to CCPT, suggesting that the study extends the indications of HFCWO for these patients in intensive care unit. (ClinicalTrials.gov number NCT02758106, retrospectively registered.) PMID:28248854

  7. Acute radiation syndrome caused by accidental radiation exposure - therapeutic principles

    Directory of Open Access Journals (Sweden)

    Dörr Harald

    2011-11-01

    Full Text Available Abstract Fortunately radiation accidents are infrequent occurrences, but since they have the potential of large scale events like the nuclear accidents of Chernobyl and Fukushima, preparatory planning of the medical management of radiation accident victims is very important. Radiation accidents can result in different types of radiation exposure for which the diagnostic and therapeutic measures, as well as the outcomes, differ. The clinical course of acute radiation syndrome depends on the absorbed radiation dose and its distribution. Multi-organ-involvement and multi-organ-failure need be taken into account. The most vulnerable organ system to radiation exposure is the hematopoietic system. In addition to hematopoietic syndrome, radiation induced damage to the skin plays an important role in diagnostics and the treatment of radiation accident victims. The most important therapeutic principles with special reference to hematopoietic syndrome and cutaneous radiation syndrome are reviewed.

  8. [A misleading form of hypersensitivity pneumonitis].

    Science.gov (United States)

    Gainet, M; Chaudemanche, H; Westeel, V; Lounici, A; Dubiez, A; Depierre, A; Dalphin, J C

    2000-11-01

    A 47-year-old woman, without significant past medical history, presented an acute dyspnea with hypoxia, marked pulmonary arterial hypertension (PAH) and signs of right heart failure. Chest x-ray showed a moderate dilatation of the right heart cavities. Pulmonary embolism was suggested. After detailed questioning and complete explorations, a bird hypersensitivity pneumonitis (HP) was demonstrated. This case illustrates a misleading presentation of an acute form of HP consisting of apparently isolated PAH.

  9. Predictors of grade {>=}2 and grade {>=}3 radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with three-dimensional conformal radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Dang, Jun; Li, Guang; Ma, Lianghua; Han, Chong; Zhang, Shuo; Yao, Lei [Dept. of Radiation Oncology, The First Hospital of China Medical Univ., Shenyang (China)], e-mail: gl1963516@yahoo.cn; Diao, Rao [Dept. of Experimental Technology Center, China Medical Univ., Shenyang (China); Zang, Shuang [Dept. of Nursing, China Medical Univ., Shenyang (China)

    2013-08-15

    Grade {>=}3 radiation pneumonitis (RP) is generally severe and life-threatening. Predictors of grade {>=}2 are usually used for grade {>=}3 RP prediction, but it is unclear whether these predictors are appropriate. In this study, predictors of grade {>=}2 and grade {>=}3 RP were investigated separately. The increased risk of severe RP in elderly patients compared with younger patients was also evaluated. Material and methods: A total of 176 consecutive patients with locally advanced non-small cell lung cancer were followed up prospectively after three-dimensional conformal radiotherapy. RP was graded according to Common Terminology Criteria for Adverse Events version 3.0. Results: Mean lung dose (MLD), mean heart dose, ratio of planning target volume to total lung volume (PTV/Lung), and dose-volume histogram comprehensive value of both heart and lung were associated with both grade {>=}2 and grade {>=}3 RP in univariate analysis. In multivariate logistic regression analysis, age and MLD were predictors of both grade {>=}2 RP and grade {>=}3 RP; receipt of chemotherapy predicted grade {>=}3 RP only; and sex and PTV/Lung predicted grade {>=}2 RP only. Among patients who developed high-grade RP, MLD and PTV/Lung were significantly lower in patients aged {>=}70 years than in younger patients (p<0.05 for both comparisons). Conclusions: The predictors were not completely consistent between grade {>=}2 RP and grade {>=}3 RP. Elderly patients had a higher risk of severe RP than younger patients did, possibly due to lower tolerance of radiation to the lung.

  10. Estimated radiation pneumonitis risk after photon versus proton therapy alone or combined with chemotherapy for lung cancer

    DEFF Research Database (Denmark)

    Vogelius, Ivan R.; Westerly, David C; Aznar, Marianne Camille

    2011-01-01

    -radiation combinations could be an interesting indication for selecting patients for proton therapy. It is likely that the IMRT plans would perform better if the CERD was accounted for during optimization, but more clinical data is required to facilitate evidence-based plan optimization in the multi-modality setting....

  11. Functional Promoter Variant rs2868371 of HSPB1 Is Associated With Risk of Radiation Pneumonitis After Chemoradiation for Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Qingsong [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Department of Radiation Oncology and Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin (China); Wei, Qingyi [Department of Epidemiology, The University of Texas MD Anderson Cancer Center (United States); Xu, Ting [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Yuan, Xianglin [Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan (China); Lopez Guerra, Jose Luis [Department of Medicine, Universitat Autònoma de Barcelona (Spain); Levy, Lawrence B. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Liu, Zhensheng [Department of Epidemiology, The University of Texas MD Anderson Cancer Center (United States); Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Zhuang, Yan [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center (United States); Wang, Li-E. [Department of Epidemiology, The University of Texas MD Anderson Cancer Center (United States); Mohan, Radhe [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center (United States); Komaki, Ritsuko [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States)

    2013-04-01

    Purpose: To date, no biomarkers have been found to predict, before treatment, which patients will develop radiation pneumonitis (RP), a potentially fatal toxicity, after chemoradiation for lung cancer. We investigated potential associations between single nucleotide polymorphisms (SNPs) in HSPB1 and risk of RP after chemoradiation for non-small cell lung cancer (NSCLC). Methods and Materials: Subjects were patients with NSCLC treated with chemoradiation at 1 institution. The training data set comprised 146 patients treated from 1999 to July 2004; the validation data set was 125 patients treated from August 2004 to March 2010. We genotyped 2 functional SNPs of HSPB1 (rs2868370 and rs2868371) from all patients. We used Kaplan-Meier analysis to assess the risk of grade ≥2 or ≥3 RP in both data sets and a parametric log-logistic survival model to evaluate the association of HSPB1 genotypes with that risk. Results: Grade ≥3 RP was experienced by 13% of those with CG/GG and 29% of those with CC genotype of HSPB1 rs2868371 in the training data set (P=.028); corresponding rates in the validation data set were 2% CG/GG and 14% CC (P=.02). Univariate and multivariate analysis confirmed the association of CC of HSPB1 rs2868371 with higher risk of grade ≥3 RP than CG/GG after adjustment for sex, age, performance status, and lung mean dose. This association was validated both in the validation data set and with Harrell's C statistic. Conclusions: The CC genotype of HSPB1 rs2868371 was associated with severe RP after chemoradiation for NSCLC.

  12. Radiation induces acute alterations in neuronal function.

    Directory of Open Access Journals (Sweden)

    Peter H Wu

    Full Text Available Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABA(ARs. These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study.

  13. A study on the pathogenesis of the radiation pneumonitis. Alterations in pulmonary mRNA encoding adhesion molecules ICAM-1, VCAM-1, and P-selectin following thoracic irradiation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tsujino, Kayoko; Kodama, Akihisa; Kono, Michio [Kobe Univ. (Japan). School of Medicine

    1997-12-01

    To investigate the role of the adhesion molecules in the pathogenesis of the radiation pneumonitis, we quantified the mRNA expression of the adhesion molecules in the lung by Northern blot method following whole thorax irradiation to C57BL/6J mice. After irradiation of 12 Gy to the whole thorax, there were increase of mRNA for ICAM-1 by 42% at 4 hours (p<0.05), 76% at 24 hours (p<0.01) and 51% at 48 hours (p<0.05) compared with controls. And it returned to control level at 1 week. No significant change was observed thereafter until 8 weeks. The expression of VCAM-1 mRNA were also increased by 49% (p<0.01) at 12 hours and were still increased by 25% at 1 week. P-selectin mRNA as transiently increased by 59% at 12 hours. We examined the relationship between the ICAM-1 induction and the radiation dose, and found that ICAM-1 expression was increased by 3 Gy of irradiation and it was increased in radiation dose dependent manner up to 24 Gy. These early inductions of mRNA for ICAM-1, VCAM-1 and P-selectin in mice lungs following thoracic irradiation were transient but significant, and they were one of the most immediate change reported in vivo. It is suggested that these adhesion molecules are possibly related to the pathogenesis of the radiation pneumonitis. (author)

  14. Bleomycin-induced pneumonitis

    NARCIS (Netherlands)

    S. Sleijfer (Stefan)

    2001-01-01

    textabstractThe cytotoxic agent bleomycin is feared for its induction of sometimes fatal pulmonary toxicity, also known as bleomycin-induced pneumonitis (BIP). The central event in the development of BIP is endothelial damage of the lung vasculature due to bleomycin-induced cytokin

  15. Using Generalized Equivalent Uniform Dose Atlases to Combine and Analyze Prospective Dosimetric and Radiation Pneumonitis Data From 2 Non-Small Cell Lung Cancer Dose Escalation Protocols

    Energy Technology Data Exchange (ETDEWEB)

    Liu Fan; Yorke, Ellen D. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Belderbos, Jose S.A.; Borst, Gerben R. [The Netherlands Cancer Institute, Antoni Van Leeuwenhoek Hospital, Amsterdam (Netherlands); Rosenzweig, Kenneth E. [Mount Sinai School of Medicine, New York, New York (United States); Lebesque, Joos V. [The Netherlands Cancer Institute, Antoni Van Leeuwenhoek Hospital, Amsterdam (Netherlands); Jackson, Andrew, E-mail: jacksona@mskcc.org [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-01-01

    Purpose: To demonstrate the use of generalized equivalent uniform dose (gEUD) atlas for data pooling in radiation pneumonitis (RP) modeling, to determine the dependence of RP on gEUD, to study the consistency between data sets, and to verify the increased statistical power of the combination. Methods and Materials: Patients enrolled in prospective phase I/II dose escalation studies of radiation therapy of non-small cell lung cancer at Memorial Sloan-Kettering Cancer Center (MSKCC) (78 pts) and the Netherlands Cancer Institute (NKI) (86 pts) were included; 10 (13%) and 14 (17%) experienced RP requiring steroids (RPS) within 6 months after treatment. gEUD was calculated from dose-volume histograms. Atlases for each data set were created using 1-Gy steps from exact gEUDs and RPS data. The Lyman-Kutcher-Burman model was fit to the atlas and exact gEUD data. Heterogeneity and inconsistency statistics for the fitted parameters were computed. gEUD maps of the probability of RPS rate {>=}20% were plotted. Results: The 2 data sets were homogeneous and consistent. The best fit values of the volume effect parameter a were small, with upper 95% confidence limit around 1.0 in the joint data. The likelihood profiles around the best fit a values were flat in all cases, making determination of the best fit a weak. All confidence intervals (CIs) were narrower in the joint than in the individual data sets. The minimum P value for correlations of gEUD with RPS in the joint data was .002, compared with P=.01 and .05 for MSKCC and NKI data sets, respectively. gEUD maps showed that at small a, RPS risk increases with gEUD. Conclusions: The atlas can be used to combine gEUD and RPS information from different institutions and model gEUD dependence of RPS. RPS has a large volume effect with the mean dose model barely included in the 95% CI. Data pooling increased statistical power.

  16. SU-E-J-251: Incorporation of Pre-Therapy 18F-FDG Uptake with CT Texture Features in a Predictive Model for Radiation Pneumonitis Development

    Energy Technology Data Exchange (ETDEWEB)

    Anthony, G; Cunliffe, A; Armato, S; Al-Hallaq, H [The University of Chicago, Chicago, IL (United States); Castillo, R [Univ Texas Medical Branch of Galveston, Pearland, TX (United States); Pham, N [Baylor College of Medicine, Houston, TX (United States); Guerrero, T [Beaumont Health System, Royal Oak, MI (United States)

    2015-06-15

    Purpose: To determine whether the addition of standardized uptake value (SUV) statistical variables to CT lung texture features can improve a predictive model of radiation pneumonitis (RP) development in patients undergoing radiation therapy. Methods: Anonymized data from 96 esophageal cancer patients (18 RP-positive cases of Grade ≥ 2) were retrospectively collected including pre-therapy PET/CT scans, pre-/posttherapy diagnostic CT scans and RP status. Twenty texture features (firstorder, fractal, Laws’ filter and gray-level co-occurrence matrix) were calculated from diagnostic CT scans and compared in anatomically matched regions of the lung. The mean, maximum, standard deviation, and 50th–95th percentiles of the SUV values for all lung voxels in the corresponding PET scans were acquired. For each texture feature, a logistic regression-based classifier consisting of (1) the average change in that texture feature value between the pre- and post-therapy CT scans and (2) the pre-therapy SUV standard deviation (SUV{sub SD}) was created. The RP-classification performance of each logistic regression model was compared to the performance of its texture feature alone by computing areas under the receiver operating characteristic curves (AUCs). T-tests were performed to determine whether the mean AUC across texture features changed significantly when SUV{sub SD} was added to the classifier. Results: The AUC for single-texturefeature classifiers ranged from 0.58–0.81 in high-dose (≥ 30 Gy) regions of the lungs and from 0.53–0.71 in low-dose (< 10 Gy) regions. Adding SUVSD in a logistic regression model using a 50/50 data partition for training and testing significantly increased the mean AUC by 0.08, 0.06 and 0.04 in the low-, medium- and high-dose regions, respectively. Conclusion: Addition of SUVSD from a pre-therapy PET scan to a single CT-based texture feature improves RP-classification performance on average. These findings demonstrate the potential for

  17. Do Angiotensin-Converting Enzyme Inhibitors Reduce the Risk of Symptomatic Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer After Definitive Radiation Therapy? Analysis of a Single-Institution Database

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongmei [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, P.R. of China (China); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang, Yan; Xu, Ting; Nguyen, Quynh-Nhu; Levy, Lawrence B.; O' Reilly, Michael [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gold, Kathryn A. [Department of Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-12-01

    Purpose: Preclinical studies have suggested that angiotensin-converting enzyme inhibitors (ACEIs) can mitigate radiation-induced lung injury. We sought here to investigate possible associations between ACEI use and the risk of symptomatic radiation pneumonitis (RP) among patients undergoing radiation therapy (RT) for non–small cell lung cancer (NSCLC). Methods and Materials: We retrospectively identified patients who received definitive radiation therapy for stages I to III NSCLC between 2004 and 2010 at a single tertiary cancer center. Patients must have received a radiation dose of at least 60 Gy for a single primary lung tumor and have had imaging and dosimetric data available for analysis. RP was quantified according to Common Terminology Criteria for Adverse Events, version 3.0. A Cox proportional hazard model was used to assess potential associations between ACEI use and risk of symptomatic RP. Results: Of 413 patients analyzed, 65 were using ACEIs during RT. In univariate analysis, the rate of RP grade ≥2 seemed lower in ACEI users than in nonusers (34% vs 46%), but this apparent difference was not statistically significant (P=.06). In multivariate analysis of all patients, ACEI use was not associated with the risk of symptomatic RP (hazard ratio [HR] = 0.66; P=.07) after adjustment for sex, smoking status, mean lung dose (MLD), and concurrent carboplatin and paclitaxel chemotherapy. Subgroup analysis showed that ACEI use did have a protective effect from RP grade ≥2 among patients who received a low (≤20-Gy) MLD (P<.01) or were male (P=.04). Conclusions: A trend toward reduction in symptomatic RP among patients taking ACEIs during RT for NSCLC was not statistically significant on univariate or multivariate analyses, although certain subgroups may benefit from use (ie, male patients and those receiving low MLD). The evidence at this point is insufficient to establish whether the use of ACEIs does or does not reduce the risk of RP.

  18. Chronic pneumonitis of infancy

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Katsumi; Kamata, Noriko; Okazaki, Eiwa [Department of Radiology, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677 (Japan); Moriyama, Sachiko; Funata, Nobuaki [Department of Pathology, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677 (Japan); Takita, Junko; Yamada, Hideo; Takayama, Naohide [Department of Pediatrics, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677 (Japan)

    2002-07-01

    Chronic pneumonitis of infancy (CPI) is a very rare lung disease in infants and young children. We report a 33-day-old infant with CPI, focusing on the radiologic aspects of the disease. Chest radiographs showed variable and non-specific appearances including ground-glass shadowing, consolidation, volume loss, and hyperinflation. Dense alveolar opacities progressed as CPI advanced. The radiologic features of our case reflected pathologic changes. (orig.)

  19. Acute effects of solar particle event radiation

    Science.gov (United States)

    Kennedy, Ann R.; Weissman, Drew; Sanzari, Jenine K.; Krigsfeld, Gabriel S.; Wan, X. Steven; Romero-Weaver, Ana L.; Diffenderfer, Eric S.; Lin, L.; Cengel, K.

    2014-01-01

    A major solar particle event (SPE) may place astronauts at significant risk for the acute radiation syndrome (ARS), which may be exacerbated when combined with other space flight stressors, such that the mission or crew health may be compromised. The National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) is focused on the assessment of risks of adverse biological effects related to the ARS in animals exposed to space flight stressors combined with the types of radiation expected during an SPE. The CARR studies are focused on the adverse biological effects resulting from exposure to the types of radiation, at the appropriate energies, doses and dose-rates, present during an SPE (and standard reference radiations: gamma rays or electrons). All animal studies described have been approved by the University of PA IACUC. Some conclusions from recent CARR investigations are as follows: (i) the relative biological effectiveness (RBE) values for SPE-like protons compared with standard reference radiations (gammas or electrons) for white blood cells (WBCs) vary greatly between mice, ferrets and pigs, with the RBE values being greater in ferrets than those in mice, and considerably greater in pigs compared with those in ferrets or mice [1, 2]. This trend for the data suggests that the RBE values for WBCs in humans could be considerably greater than those observed in small mammals, and SPE proton radiation may be far more hazardous to humans than previously estimated from small animal studies. (ii) Very low doses of SPE proton radiation (25 cGy) increase blood clotting times in ferrets, and the low SPE-like dose rate has more severe effects than high dose rate radiation [3]. (iii) Results from pig and ferret studies suggest that disseminated intravascular coagulation is a major cause of death at doses near the LD50 level for SPE-like proton and gamma radiation. (iv) Exposure to SPE-like proton or gamma radiation, in combination with

  20. 放射性肺炎CT灌注成像的临床研究%Application of CT perfusion imaging in radiation pneumonitis

    Institute of Scientific and Technical Information of China (English)

    翟小明; 王建平; 张军宁; 顾科

    2008-01-01

    Objective To investigate the relation between the change of perfusion parameter values and the formation of radiation pneumonitis (RP), with the technique of CT peffusion imaging (CTPI). Methods Sixty-four slices spiral CTPI were performed in 37 patients with thoracic tumor before and after irradiation with different doses in different phases. And varied perfusion parameters of region of interest (ROI) in lung tissue were assessed such as blood flow (BF), blood volume(BV), time to peak(TIP), permeabihty surface(PS), mean transit time (MTT) and relative values of these parameters were calculated, i. e, rBF, rBV, rTTP, rPS, rMTT. Results The perfusion parameters of non-tumor peripheral lung tissue before irradiation had no difference among lung or non-lung cancer and different gender as well. RP occurred in the eases with the remarkable boost in rBF, rBV and rPS (the value of F was 5.552,8.495 and 14.951 respectively, P<0.05), while RP would not happen ff rBF significantly ascended only(F=9.146, P< 0.05). Conclusions The rule of perfusion change of lung tissue after irradiation could be detected with CTPI and it had been demonstrated that the application of CTPI in studying lung perfusion and RP was valuable. The parameters such as rBF, rBV and rPS had an important role in forecasting RP.%目的 采用CT灌注成像(CTPI)技术,探求放射性肺炎(RP)形成的CTPI特点,为预测RP提供依据.方法 对37例胸部肿瘤患者照射前后不同时期行64排螺旋CT灌注成像扫描,得到肺组织感兴趣区(ROI)内各灌注参数值,即血流量(BF)、血容量(BV)、峰值时间(TTP)、表面通透性(PS)、平均通过时间(MTT),进而计算出各灌注参数相对值(rBF、rBV、rTTP、rPS、rMTT).结果 放疗前,肺癌及其他胸部肿瘤患者的非瘤周肺组织灌注值BF、BV、TTP及MTT均无差异,与性别无关(t值分别为0.643、1.541、0.470及1.199,P0.05),与左右肺也无关(t值分别为0.857、0.346、0.470及1.656,P0.05);放疗后,rBF

  1. Health Impacts from Acute Radiation Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Strom, Daniel J.

    2003-09-30

    Absorbed doses above1-2 Gy (100-200 rads) received over a period of a day or less lead to one or another of the acute radiation syndromes. These are the hematopoietic syndrome, the gastrointestinal (GI) syndrome, the cerebrovascular (CV) syndrome, the pulmonary syndrome, or the cutaneous syndrome. The dose that will kill about 50% of the exposed people within 60 days with minimal medical care, LD50-60, is around 4.5 Gy (450 rads) of low-LET radiation measured free in air. The GI syndrome may not be fatal with supportive medical care and growth factors below about 10 Gy (1000 rads), but above this is likely to be fatal. Pulmonary and cutaneous syndromes may or may not be fatal, depending on many factors. The CV syndrome is invariably fatal. Lower acute doses, or protracted doses delivered over days or weeks, may lead to many other health outcomes than death. These include loss of pregnancy, cataract, impaired fertility or temporary or permanent sterility, hair loss, skin ulceration, local tissue necrosis, developmental abnormalities including mental and growth retardation in persons irradiated as children or fetuses, radiation dermatitis, and other symptoms listed in Table 2 on page 12. Children of parents irradiated prior to conception may experience heritable ill-health, that is, genetic changes from their parents. These effects are less strongly expressed than previously thought. Populations irradiated to high doses at high dose rates have increased risk of cancer incidence and mortality, taken as about 10-20% incidence and perhaps 5-10% mortality per sievert of effective dose of any radiation or per gray of whole-body absorbed dose low-LET radiation. Cancer risks for non-uniform irradiation will be less.

  2. Acute adaptive immune response correlates with late radiation-induced pulmonary fibrosis in mice.

    Science.gov (United States)

    Paun, Alexandra; Kunwar, Amit; Haston, Christina K

    2015-02-20

    The lung response to radiation exposure can involve an immediate or early reaction to the radiation challenge, including cell death and an initial immune reaction, and can be followed by a tissue injury response, of pneumonitis or fibrosis, to this acute reaction. Herein, we aimed to determine whether markers of the initial immune response, measured within days of radiation exposure, are correlated with the lung tissue injury responses occurring weeks later. Inbred strains of mice known to be susceptible (KK/HIJ, C57BL/6J, 129S1/SvImJ) or resistant (C3H/HeJ, A/J, AKR/J) to radiation-induced pulmonary fibrosis and to vary in time to onset of respiratory distress post thoracic irradiation (from 10-23 weeks) were studied. Mice were untreated (controls) or received 18 Gy whole thorax irradiation and were euthanized at 6 h, 1d or 7 d after radiation treatment. Pulmonary CD4+ lymphocytes, bronchoalveolar cell profile & cytokine level, and serum cytokine levels were assayed. Thoracic irradiation and inbred strain background significantly affected the numbers of CD4+ cells in the lungs and the bronchoalveolar lavage cell differential of exposed mice. At the 7 day timepoint greater numbers of pulmonary Th1 and Th17 lymphocytes and reduced lavage interleukin17 and interferonγ levels were significant predictors of late stage fibrosis. Lavage levels of interleukin-10, measured at the 7 day timepoint, were inversely correlated with fibrosis score (R=-0.80, p=0.05), while serum levels of interleukin-17 in control mice significantly correlated with post irradiation survival time (R=0.81, p=0.04). Lavage macrophage, lymphocyte or neutrophil counts were not significantly correlated with either of fibrosis score or time to respiratory distress in the six mouse strains. Specific cytokine and lymphocyte levels, but not strain dependent lavage cell profiles, were predictive of later radiation-induced lung injury in this panel of inbred strains.

  3. Medical management of the acute radiation syndrome.

    Science.gov (United States)

    López, Mario; Martín, Margarita

    2011-07-13

    The acute radiation syndrome (ARS) occurs after whole-body or significant partial-body irradiation (typically at a dose of >1 Gy). ARS can involve the hematopoietic, cutaneous, gastrointestinal and the neurovascular organ systems either individually or in combination. There is a correlation between the severity of clinical signs and symptoms of ARS and radiation dose. Radiation induced multi-organ failure (MOF) describes the progressive dysfunction of two or more organ systems over time. Radiation combined injury (RCI) is defined as radiation injury combined with blunt or penetrating trauma, burns, blast, or infection. The classic syndromes are: hematopoietic (doses >2-3 Gy), gastrointestinal (doses 5-12 Gy) and cerebrovascular syndrome (doses 10-20 Gy). There is no possibility to survive after doses >10-12 Gy. The Phases of ARS are-prodromal: 0-2 days from exposure, latent: 2-20 days, and manifest illness: 21-60 days from exposure. Granulocyte-colony stimulating factor (G-CSF) at a dose of 5 μg/kg body weight per day subcutaneously has been recommended as treatment of neutropenia, and antibiotics, antiviral and antifungal agents for prevention or treatment of infections. If taken within the first hours of contamination, stable iodine in the form of nonradioactive potassium iodide (KI) saturates iodine binding sites within the thyroid and inhibits incorporation of radioiodines into the gland. Finally, if severe aplasia persists under cytokines for more than 14 days, the possibility of a hematopoietic stem cell (HSC) transplantation should be evaluated. This review will focus on the clinical aspects of the ARS, using the European triage system (METREPOL) to evaluate the severity of radiation injury, and scoring groups of patients for the general and specific management of the syndrome.

  4. Intensity-modulated radiotherapy might increase pneumonitis risk relative to three-dimensional conformal radiotherapy in patients receiving combined chemotherapy and radiotherapy

    DEFF Research Database (Denmark)

    Vogelius, Ivan S; Westerly, David C; Cannon, George M;

    2011-01-01

    To model the possible interaction between cytotoxic chemotherapy and the radiation dose distribution with respect to the risk of radiation pneumonitis.......To model the possible interaction between cytotoxic chemotherapy and the radiation dose distribution with respect to the risk of radiation pneumonitis....

  5. Do Angiotensin-Converting Enzyme Inhibitors Reduce the Risk of Symptomatic Radiation Pneumonitis in Patients with Non-small Cell Lung Cancer after Definitive Radiotherapy? Analysis of a Single-Institution Database

    Science.gov (United States)

    Wang, Hongmei; Liao, Zhongxing; Zhuang, Yan; Xu, Ting; Nguyen, Quynh-Nhu; Levy, Lawrence B.; O'eilly, Michael S.; Gold, Kathryn A.; Gomez, Daniel R.

    2014-01-01

    Purpose Preclinical studies have suggested that angiotensin-converting enzyme inhibitors (ACEIs) can mitigate radiation-induced lung injury. We sought here to investigate possible associations between ACEI use and the risk of symptomatic radiation pneumonitis (RP) among patients undergoing radiation therapy (RT) for non–small-cell lung cancer (NSCLC). Patients and Methods We retrospectively identified patients who received definitive radiotherapy for stage I–III NSCLC in 2004–2010 at a single tertiary cancer center. Patients must have received a radiation dose of at least 60 Gy for a single primary lung tumor and have had imaging and dosimetric data available for analysis. RP was quantified according to the Common Terminology Criteria for Adverse Events v3.0. A Cox proportional hazard model was used to assess potential associations between ACEI use and risk of symptomatic RP. Results Of the 413 patients analyzed, 65 were using ACEIs during RT. In univariate analysis, the rate of grade ⩾2 RP seemed lower in ACEI users than in nonusers (34% vs 46%), but this apparent difference was not statistically significant (P=0.06). In multivariate analysis of all patients, ACEI use was not associated with the risk of symptomatic RP (hazard ratio [HR]=0.66, P=0.07) after adjustment for sex, smoking status, mean lung dose (MLD), and concurrent carboplatin and paclitaxel chemotherapy. Subgroup analysis showed that ACEI use did have a protective effect from grade ≥2 RP among patients who received a low (⩽;20 Gy) MLD (PACEIs during RT for NSCLC was not statistically significant on univariate or multivariate analyses, though certain subgroups may benefit from use (i.e., male patients and those with low MLD). The evidence at this point is insufficient to establish whether the use of ACEIs does or does not reduce the risk of RP. PMID:24161424

  6. Acute Cerebrovascular Radiation Syndrome: Radiation Neurotoxicity , mechanisms of CNS radiation injury, advanced countermeasures for Radiation Protection of Central Nervous System.

    Science.gov (United States)

    Popov, Dmitri; Jones, Jeffrey; Maliev, Slava

    Key words: Cerebrovascular Acute Radiation Syndrome (Cv ARS), Radiation Neurotoxins (RNT), Neurotransmitters, Radiation Countermeasures, Antiradiation Vaccine (ArV), Antiradiation Blocking Antibodies, Antiradiation Antidote. Psychoneuroimmunology, Neurotoxicity. ABSTRACT: To review the role of Radiation Neurotoxins in triggering, developing of radiation induced central nervous system injury. Radiation Neurotoxins - rapidly acting blood toxic lethal agent, which activated after irradiation and concentrated, circulated in interstitial fluid, lymph, blood with interactions with cell membranes, receptors and cell compartments. Radiation Neurotoxins - biological molecules with high enzymatic activity and/or specific lipids and activated or modified after irradiation. The Radiation Neurotoxins induce increased permeability of blood vessels, disruption of the blood-brain barrier, blood-cerebrospinal fluid (CSF) barrier and developing severe disorder of blood macro- and micro-circulation. Principles of Radiation Psychoneuro-immunology and Psychoneuro-allergology were applied for determination of pathological processes developed after irradiation or selective administration of Radiation Neurotoxins to radiation naïve mammals. Effects of radiation and exposure to radiation can develop severe irreversible abnormalities of Central Nervous System, brain structures and functions. Antiradiation Vaccine - most effective, advanced methods of protection, prevention, mitigation and treatment and was used for of Acute Radiation Syndromes and elaboration of new technology for immune-prophylaxis and immune-protection against ϒ, Heavy Ion, Neutron irradiation. Results of experiments suggested that blocking, antitoxic, antiradiation antibodies can significantly reduce toxicity of Radiation Toxins. New advanced technology include active immune-prophylaxis with Antiradiation Vaccine and Antiradiation therapy that included specific blocking antibodies to Radiation Neurotoxins

  7. The cognitive profile of children treated with radiation for acute ...

    African Journals Online (AJOL)

    The cognitive profile of children treated with radiation for acute lymphoblastic ... educated in their second language were included in the cognitive evaluation. ... of their treatment protocol and were on maintenance treatment at the time of the ...

  8. Influenza SIRS with Minimal Pneumonitis.

    Science.gov (United States)

    Erramilli, Shruti; Mannam, Praveen; Manthous, Constantine A

    2016-01-01

    Although systemic inflammatory response syndrome (SIRS) is a known complication of severe influenza pneumonia, it has been reported very rarely in patients with minimal parenchymal lung disease. We here report a case of severe SIRS, anasarca, and marked vascular phenomena with minimal or no pneumonitis. This case highlights that viruses, including influenza, may cause vascular dysregulation causing SIRS, even without substantial visceral organ involvement.

  9. Acute radiation proctitis. A clinical, histopathological and histochemical study

    Energy Technology Data Exchange (ETDEWEB)

    Hovdenak, Nils

    2004-07-01

    The aim of the study is: 1) A sequential description of the clinical course of acute radiation proctitis during pelvic RT. 2) A sequential description of the rectal mucosal histopathology during pelvic RT as a possible substrate for clinical toxicity. 3) To assess the mucosal protease activity during RT as a possible explanation of the observed tissue changes. 4) To assess the efficacy of prophylactic sucralfate in acute radiation proctitis a randomised study was initiated and carried out together with a meta-analysis of previously available data. 5) Most studies on clinical acute toxicity in pelvic RT use either the RTOG/EORTC score system or focus on diarrhoea/stool frequency. A more differentiated and sensitive recording was developed and tested to pick up symptoms escaping the commonly used scores. 6) Study the relation between histopathological findings and the clinical picture. 4 papers presenting various studies are included. The titles are: 1) Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy. 2) Clinical significance of increased gelatinolytic activity in the rectal mucosa during external beam radiation therapy of prostate cancer. 3) Profiles and time course of acute radiation toxicity symptoms during conformal radiotherapy for cancer of the prostate. 4) Sucralfate does not ameliorate acute radiation proctitis. Some future prospects are discussed.

  10. Lupus pneumonitis as the initial presentation of systemic lupus erythematosus: case series from a single institution.

    Science.gov (United States)

    Wan, S A; Teh, C L; Jobli, A T

    2016-11-01

    Objective The aim of this study was to examine the clinical features, treatment and outcome of systemic lupus erythematosus (SLE) patients in our centre who presented with lupus pneumonitis as the initial manifestation. Methods We performed a retrospective review of all patients who presented with lupus pneumonitis during the initial SLE manifestation from March 2006 to March 2015. Results There were a total of five patients in our study who presented with fever and cough as the main clinical features. All patients had pulmonary infiltrates on chest radiographs. High-resolution computed tomography, which was performed in two patients, showed ground glass opacities with patchy consolidations bilaterally. All patients received high-dose steroids, 80% received intravenous cyclophosphamide and 60% received intravenous immunoglobulin. Two patients died from severe lupus pneumonitis within 2 weeks of admission despite treatment with ventilation, steroids, cyclophosphamide and intravenous immunoglobulin. Conclusions Acute lupus pneumonitis is an uncommon presentation of SLE. Mortality in this case series is 40%.

  11. Interstitial pneumonitis following intrapleural chemotherapy

    Directory of Open Access Journals (Sweden)

    Humphries Gary N

    2009-02-01

    Full Text Available Abstract Background Mucinous neoplasms within the abdomen may disseminate by direct extension through the diaphragm to involve the pleural space. Treatment of this condition is by parietal and visceral pleurectomy followed by hyperthermic intrapleural chemotherapy. Case presentation In this case report a patient developed persistent right upper lobe interstitial pneumonitis and progressive parenchymal fibrosis following intrapleural chemotherapy treatment with mitomycin C and doxrubicin. The condition persisted until death 28 months later. Death was from progressive intraabdominal disease with intestinal obstruction and sepsis associated with progressive pulmonary parenchymal disease. The right pleural space disease did not recur. Conclusion This manuscript is the first case report describing interstitial pneumonitis and lung fibrosis following intrapleural chemotherapy. Since pulmonary toxicity from chemotherapy is a dose-dependent phenomenon, dose reduction of intrapleural as compared to intraperitoneal hyperthermic chemotherapy may be necessary.

  12. Antiradiation Vaccine: Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava

    Introduction: Current medical management of the Acute Radiation Syndromes (ARS) does not include immune prophylaxis based on the Antiradiation Vaccine. Existing principles for the treatment of acute radiation syndromes are based on the replacement and supportive therapy. Haemotopoietic cell transplantation is recomended as an important method of treatment of a Haemopoietic form of the ARS. Though in the different hospitals and institutions, 31 pa-tients with a haemopoietic form have previously undergone transplantation with stem cells, in all cases(100%) the transplantants were rejected. Lethality rate was 87%.(N.Daniak et al. 2005). A large amount of biological substances or antigens isolated from bacterias (flagellin and derivates), plants, different types of venom (honeybees, scorpions, snakes) have been studied. This biological active substances can produce a nonspecific stimulation of immune system of mammals and protect against of mild doses of irradiation. But their radioprotection efficacy against high doses of radiation were not sufficient. Relative radioprotection characteristics or adaptive properties of antioxidants were expressed only at mild doses of radiation. However antioxidants demonstrated a very low protective efficacy at high doses of radiation. Some ex-periments demonstrated even a harmful effect of antioxidants administered to animals that had severe forms of the ARS. Only Specific Radiation Toxins roused a specific antigenic stim-ulation of antibody synthesis. An active immunization by non-toxic doses of radiation toxins includes a complex of radiation toxins that we call the Specific Radiation Determinant (SRD). Immunization must be provided not less than 24 days before irradiation and it is effective up to three years and more. Active immunization by radiation toxins significantly reduces the mortality rate (100%) and improves survival rate up to 60% compare with the 0% sur-vival rate among the irradiated animals in control groups

  13. Influenza SIRS with minimal pneumonitis

    Directory of Open Access Journals (Sweden)

    Shruti Erramilli

    2016-08-01

    Full Text Available While systemic inflammatory response syndrome (SIRS, is a known complication of severe influenza pneumonia, it has been reported very rarely in patients with minimal parenchymal lung disease. We here report a case of severe SIRS, anasarca and marked vascular phenomena with minimal or no pneumonitis. This case highlights that viruses, including influenza, may cause vascular dysregulation causing SIRS, even without substantial visceral organ involvement.

  14. Acute radiation disease and biological dosimetry in 1993.

    Science.gov (United States)

    Vorobiev, A I

    1997-01-01

    Mankind is at risk for accidental exposure to ionizing radiation. The experience in evaluating and treating victims of radiation exposure is briefly reviewed based upon accidents occurring over the past 25 years. Individual cases of acute toxicities to the skin, gastrointestinal tract, liver and bone marrow are presented. Biodosimetry (utilizing chromosome analysis of peripheral blood lymphocytes and bone marrow and electron spin resonance spectrometry of dental enamel) has been utilized in radiation accidents to assess individual dose. Variability in the dose of ionizing radiation received is typical among the population affected by the Chernobyl accident. Whereas the acute radiation syndrome resulting in a high mortality has been well-documented, little information is available regarding the effects of chronic, low-level exposure from the Chernobyl accident.

  15. 老年肺癌放疗唤起性肺炎2例并文献复习%Radiation recall pneumonitis:report of 2 cases and review of literatures

    Institute of Scientific and Technical Information of China (English)

    钱小顺; 刘庆辉; 孙宝君

    2012-01-01

    Objective To explore the diagnosis and treatment of radiation recall pneumonitis(RRP) in elderly. Methods The diagnosis and treatment of two cases of RRP induced by targeted medicines and antibiotics after radiotherapy for lung cancer was reviewed. Results Diagnosis of RRP induced by erlotinib and levofloxacin after thoracic radiotherapy was established for the two elderly patients with lung cancer. Symptomatic and radiographic improvement was observed after withdrawal of induced drugs and application of corticosteroids. Conclusions Doctor should pay attention to RRP on the aged patients treated with antibiotics and antineoplastics after radiotherapy.%目的 探讨老年人放疗唤起性肺炎的诊断和治疗.方法 报告了2例老年肺癌患者放疗后应用靶向药物和抗生素治疗引起放疗唤起性肺炎的诊治过程.结果 2例老年肺癌患者均接受放射治疗,在其后续治疗中发生放疗唤起性肺炎,诱导药物分别为厄洛替尼、左氧氟沙星和头孢哌酮舒巴坦.停用诱导药物和加用糖皮质激素治疗后,患者临床症状改善、肺部阴影吸收.结论 放疗唤起性肺炎是一种罕见疾病,临床上容易误诊和漏诊,老年肺癌患者在接受放射治疗后的后续治疗中一定要警惕其发生.

  16. Acute radiation syndrones and their management

    Energy Technology Data Exchange (ETDEWEB)

    Cronkite, E.P.

    1988-01-01

    Radiation syndromes produced by large doses of ionizing radiation are divided into three general groups depending on dose of radiation and time after exposure. The CNS syndrome requires many thousands of rad, appears in minutes to hours, and kills within hours to days. The GIS appears after doses of a few hundred to 2000 rad. It is characterized by nausea, vomiting, diarrhea, and disturbances of water and electrolyte metabolism. It has a high mortality in the first week after exposure. Survivors will then experience the HS as a result of marrow aplasia. Depending on dose, survival is possible with antibiotic and transfusion therapy. The relationship of granulocyte depression to mortality in dogs and human beings is illustrated. The role of depth dose pattern of mortality of radiation exposure is described and used as an indication of why air exposure doses may be misleading. The therapy of radiation injury is described based on antibiotics, transfusion therapy, and use of molecular regulators. The limited role of matched allogenic bone marrow transplants is discussed. 52 refs., 13 figs.

  17. Physiological Mechanisms of Acute Intestinal Radiation Death

    Science.gov (United States)

    1986-06-01

    Radiation Death 18 3 1 A eutron 19 ABSTRACT (Contfnuo on rlvorJ of re.•u•ldy ,d d..nfflfy by blo*,t ftmO,) e overall objective was to claikUTyhe role...neutron kerma rates. These changes are attributable to attenuation of neutrons and the production of gamma rays by thermal neutroncapture by hydrogen in...but also injuries from blast and thermal effects. These non-ionizing radiation traumas can result in sequestering large amounts of fluid and

  18. Emetic Mechanism in Acute Radiation Sickness

    Science.gov (United States)

    1987-08-20

    emetic effect of radiation in a single episode recorded from the thoracic cavity consists typically of two phases. Initial repetitive negative...three additional cats, all combined with vagotomy. Wang et al. (1958) found no effect at all of "abdominal sympathectomy " performed as the sole...Wang and Borison (1951) performed total sympathectomies in dogs. We therefore now find uninterpretable the results of "abdominal sympathectomy " in the

  19. Migratory pneumonitis similar to bronchiolitis obliterans organizing pneumonia after conservative treatment of breast cancer. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura, Kanji; Hirokawa, Yutaka; Matsuura, Akiko; Akagi, Yukio; Ito, Katsuhide [Hiroshima Univ. (Japan). School of Medicine

    1999-07-01

    We report the case of a 63-year-old woman who developed cough and fever with migratory lung infiltrates three months after completion of right breast irradiation following conservative surgery. Lung infiltrates were initially localized in the irradiated area, but later spread to unirradiated areas in both lungs. No cause of migratory pneumonitis other than irradiation was found, and we clinically diagnosed this case as radiation-induced migratory pneumonitis similar to Bronchiolitis Obliterans Organizing Pneumonia(BOOP), without lung biopsy. Steroid therapy resulted incomplete resolution of lung infiltrates. The reported case clearly differed from typical radiation pneumonitis. We suggest that lung irradiation might trigger the development of migratory pneumonitis with a clinical pattern similar to that of BOOP. (author)

  20. Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava

    Introduction: Cerebrovascular Acute Radiation Syndrome (CvARS) is an extremely severe in-jury of Central Nervous System (CNS) and Peripheral Nervous System (PNS). CvARS can be induced by the high doses of neutron, heavy ions, or gamma radiation. The Syndrome clinical picture depends on a type, timing, and the doses of radiation. Four grades of the CvARS were defined: mild, moderate, severe, and extremely severe. Also, four stages of CvARS were developed: prodromal, latent, manifest, outcome -death. Duration of stages depends on the types, doses, and time of radiation. The CvARS clinical symptoms are: respiratory distress, hypotension, cerebral edema, severe disorder of cerebral blood microcirculation, and acute motor weakness. The radiation toxins, Cerebro-Vascular Radiation Neurotoxins (SvARSn), determine development of the acute radiation syndrome. Mechanism of action of the toxins: Though pathogenesis of radiation injury of CNS remains unknown, our concept describes the Cv ARS as a result of Neurotoxicity and Excitotoxicity, cell death through apoptotic necrosis. Neurotoxicity occurs after the high doses radiation exposure, formation of radiation neuro-toxins, possible bioradicals, or group of specific enzymes. Intracerebral hemorrhage can be a consequence of the damage of endothelial cells caused by radiation and the radiation tox-ins. Disruption of blood-brain barrier (BBB)and blood-cerebrospinal fluid barrier (BCFB)is possibly the most significant effect of microcirculation disorder and metabolic insufficiency. NMDA-receptors excitotoxic injury mediated by cerebral ischemia and cerebral hypoxia. Dam-age of the pyramidal cells in layers 3 and 5 and Purkinje cell layer the cerebral cortex , damage of pyramidal cells in the hippocampus occur as a result of cerebral ischemia and intracerebral bleeding. Methods: Radiation Toxins of CV ARS are defined as glycoproteins with the molec-ular weight of RT toxins ranges from 200-250 kDa and with high enzymatic activity

  1. Rheumatoid arthritis and cryptogenic organising pneumonitis.

    Science.gov (United States)

    Rees, J H; Woodhead, M A; Sheppard, M N; du Bois, R M

    1991-05-01

    We describe three patients with rheumatoid arthritis who presented with non-specific pulmonary symptoms, a restrictive defect in lung function and bilateral changes on chest radiograph. Lung histology showed characteristic features of cryptogenic organising pneumonitis and treatment with steroids produced significant improvement. The clinical and laboratory features of cryptogenic organising pneumonitis (otherwise known as bronchiolitis obliterans organising pneumonia, 'BOOP') are discussed and compared with those of bronchiolitis obliterans with which the condition should not be confused. Cryptogenic organising pneumonitis should be considered as one of the pulmonary manifestations of rheumatoid arthritis, but lung biopsy is essential to make the diagnosis.

  2. [Hypersensitivity Pneumonitis (extrinsic allergic alveolitis)].

    Science.gov (United States)

    Cebollero, P; Echechipía, S; Echegoyen, A; Lorente, M P; Fanlo, P

    2005-01-01

    Farmer's lung was first described in 1932. We can define hypersensitivity pneumonitis as a pulmonary and systemic disease that is accompanied by dyspnoea and coughing; it is caused by an immunological type of inflammation of the alveolar walls and the terminal airways and it is secondary to the repeated inhalation of a variety of antigens by a susceptible host. It can be said that it is an underdiagnosed disease and only a high degree of clinical manifestations and a detailed history of exposure can lead to an early diagnosis and satisfactory treatment. A combination among clinical-radiological, functional, cytological or pathological findings leads in some cases to a diagnosis. Treatment is based on avoiding further exposure to the causal agent and in the more serious cases the administration of systemic corticoid treatment.

  3. Thalidomide effect in endothelial cell of acute radiation proctitis

    Institute of Scientific and Technical Information of China (English)

    Ki-Tae Kim; Hiun-Suk Chae; Jin-Soo Kim; Hyung-Keun Kim; Young-Seok Cho; Whang Choi; Kyu-Yong Choi; Sang-Young Rho; Suk-Jin Kang

    2008-01-01

    AIM: To determine whether thalidomide prevents microvascular injury in acute radiation proctitis in white rats. METHODS: Fourteen female Wistar rats were used:six in the radiation group,six in the thalidomide group,and two in normal controls.The radiation and thalidomide groups were irradiated at the pelvic area using a single 30 Gy exposure.The thalidomide (150 mg/kg) was injected into the peritoneum for 7 d from the day of irradiation.All animals were sacrificed and the rectums were removed on day 8 after irradiation.The microvessels of resected specimens were immunohistochemically stained with thrombomodulin (TM),yon Willebrand Factor (vWF),and vascular endothelial growth factor (VEGF).RESULTS: The microscopic scores did not differ significantly between the radiation and thalidomide groups,but both were higher than in the control group.Expression of TM was significantly lower in the endothelial cells (EC) of the radiation group than in the control and thalidomide groups (P < 0.001).The number of capillaries expressing vWF in the EC was higher in the radiation group (15.3 ± 6.8) than in the control group (3.7 ± 1.7),and the number of capillaries expressing vWF was attenuated by thalidomide (10.8 ± 3.5,P < 0.001).The intensity of VEGF expression in capillaries was greater in the radiation group than in the control group and was also attenuated by thalidomide (P = 0.003).CONCLUSION: The mechanisms of acute radiationinduced proctitis in the rats are related to endothelial cell injury of microvessel,which may be attenuated with thalidomide.

  4. Acute Radiation Effects Resulting from Exposure to Solar Particle Event-Like Radiation

    Science.gov (United States)

    Kennedy, Ann; Cengel, Keith

    2012-07-01

    A major solar particle event (SPE) may place astronauts at significant risk for the acute radiation syndrome (ARS), which may be exacerbated when combined with other space flight stressors, such that the mission or crew health may be compromised. The National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) is focused on the assessment of risks of adverse biological effects related to the ARS in animal models exposed to space flight stressors combined with the types of radiation expected during an SPE. As part of this program, FDA-approved drugs that may prevent and/or mitigate ARS symptoms are being evaluated. The CARR studies are focused on the adverse biological effects resulting from exposure to the types of radiation, at the appropriate energies, doses and dose-rates, present during an SPE (and standard reference radiations, gamma rays or electrons). The ARS is a phased syndrome which often includes vomiting and fatigue. Other acute adverse biologic effects of concern are the loss of hematopoietic cells, which can result in compromised bone marrow and immune cell functions. There is also concern for skin damage from high SPE radiation doses, including burns, and resulting immune system dysfunction. Using 3 separate animal model systems (ferrets, mice and pigs), the major ARS biologic endpoints being evaluated are: 1) vomiting/retching and fatigue, 2) hematologic changes (with focus on white blood cells) and immune system changes resulting from exposure to SPE radiation with and without reduced weightbearing conditions, and 3) skin injury and related immune system functions. In all of these areas of research, statistically significant adverse health effects have been observed in animals exposed to SPE-like radiation. Countermeasures for the management of ARS symptoms are being evaluated. New research findings from the past grant year will be discussed. Acknowledgements: This research is supported by the NSBRI Center of Acute

  5. High-resolution computed tomography and histopathological findings in hypersensitivity pneumonitis: a pictorial essay*

    Science.gov (United States)

    Torres, Pedro Paulo Teixeira e Silva; Moreira, Marise Amaral Rebouças; Silva, Daniela Graner Schuwartz Tannus; da Gama, Roberta Rodrigues Monteiro; Sugita, Denis Masashi; Moreira, Maria Auxiliadora do Carmo

    2016-01-01

    Hypersensitivity pneumonitis is a diffuse interstitial and granulomatous lung disease caused by the inhalation of any one of a number of antigens. The objective of this study was to illustrate the spectrum of abnormalities in high-resolution computed tomography and histopathological findings related to hypersensitivity pneumonitis. We retrospectively evaluated patients who had been diagnosed with hypersensitivity pneumonitis (on the basis of clinical-radiological or clinical-radiological-pathological correlations) and had undergone lung biopsy. Hypersensitivity pneumonitis is clinically divided into acute, subacute, and chronic forms; high-resolution computed tomography findings correlate with the time of exposure; and the two occasionally overlap. In the subacute form, centrilobular micronodules, ground-glass opacities, and air trapping are characteristic high-resolution computed tomography findings, whereas histopathology shows lymphocytic inflammatory infiltrates, bronchiolitis, variable degrees of organizing pneumonia, and giant cells. In the chronic form, high-resolution computed tomography shows traction bronchiectasis, honeycombing, and lung fibrosis, the last also being seen in the biopsy sample. A definitive diagnosis of hypersensitivity pneumonitis can be made only through a multidisciplinary approach, by correlating clinical findings, exposure history, high-resolution computed tomography findings, and lung biopsy findings. PMID:27141134

  6. High-resolution computed tomography and histopathological findings in hypersensitivity pneumonitis: a pictorial essay

    Energy Technology Data Exchange (ETDEWEB)

    Torres, Pedro Paulo Teixeira e Silva; Moreira, Marise Amaral Reboucas; Silva, Daniela Graner Schuwartz Tannus; Moreira, Maria Auxiliadora do Carmo [Universidade Federal de Goias (UFG), Goiania, GO (Brazil); Gama, Roberta Rodrigues Monteiro da [Hospital do Cancer de Barretos, Barretos, SP (Brazil); Sugita, Denis Masashi, E-mail: pedroptstorres@yahoo.com.br [Anapolis Unievangelica, Anapolis, GO (Brazil)

    2016-03-15

    Hypersensitivity pneumonitis is a diffuse interstitial and granulomatous lung disease caused by the inhalation of any one of a number of antigens. The objective of this study was to illustrate the spectrum of abnormalities in high-resolution computed tomography and histopathological findings related to hypersensitivity pneumonitis. We retrospectively evaluated patients who had been diagnosed with hypersensitivity pneumonitis (on the basis of clinical-radiological or clinical-radiological-pathological correlations) and had undergone lung biopsy. Hypersensitivity pneumonitis is clinically divided into acute, subacute, and chronic forms; high-resolution computed tomography findings correlate with the time of exposure; and the two occasionally overlap. In the subacute form, centrilobular micronodules, ground glass opacities, and air trapping are characteristic high-resolution computed tomography findings, whereas histopathology shows lymphocytic inflammatory infiltrates, bronchiolitis, variable degrees of organizing pneumonia, and giant cells. In the chronic form, high-resolution computed tomography shows traction bronchiectasis, honeycombing, and lung fibrosis, the last also being seen in the biopsy sample. A definitive diagnosis of hypersensitivity pneumonitis can be made only through a multidisciplinary approach, by correlating clinical findings, exposure history, high-resolution computed tomography findings, and lung biopsy findings. (author)

  7. Multifocal atherosclerosis in patient after acute first degree radiation sickness.

    Directory of Open Access Journals (Sweden)

    Metlyaeva N.A.

    2014-12-01

    Full Text Available Purpose: assessment the heavy psychosomatic and all-somatic cardiovascular and cerebrovascular pathology of patient, transferred an acute I degree radiation sickness, from the general evenly gamma-beta radiation. Conclusions. The subdepressive and disturbing-depressive syndrome of patient, transferred an acute radiation sickness (ARS of I degree, from the general evenly gamma-beta radiation, was independent risk factor of development of multifocal atherosclerosis; Features of development of all-somatic and psychosomatic pathology of patient are based on a combination of genetic prerequisites, environment influences (the stress caused by accident on the ChNPP and social factors, influencing on him during a course of life, especially during early socialization. Thus at development of psychosomatic frustration the combination of feature of the mental reaction connected with the personal characteristic and special relationship between mental (stress and physiological (somatic by aspects of reaction which led to metabolism violation, to aging, decrease in adaptation opportunities of an organism and development age — dependent pathology took place.

  8. Acute radiation enteritis caused by dose-dependent radiation exposure in dogs: experimental research.

    Science.gov (United States)

    Xu, Wenda; Chen, Jiang; Xu, Liu; Li, Hongyu; Guo, Xiaozhong

    2014-12-01

    Accidental or intended radiation exposure in mass casualty settings presents a serious and on-going threat. The development of mitigating and treating agents requires appropriate animal models. Unfortunately, the majority of research on radiation enteritis in animals has lacked specific assessments and targeted therapy. Our study showed beagle dogs, treated by intensity-modulated radiation therapy (IMRT) for abdominal irradiation, were administered single X-ray doses of 8-30 Gy. The degree of intestinal tract injury for all of the animals after radiation exposure was evaluated with regard to clinical syndrome, endoscopic findings, histological features, and intestinal function. The range of single doses (8 Gy, 10-14 Gy, and 16-30 Gy) represented the degree of injury (mild, moderate, and severe, respectively). Acute radiation enteritis included clinical syndrome with fever, vomiting, diarrhea, hemafecia, and weight loss; typical endoscopic findings included edema, bleeding, mucosal abrasions, and ulcers; and intestinal biopsy results revealed mucosal necrosis, erosion, and loss, inflammatory cell infiltration, hemorrhage, and congestion. Changes in serum diamine oxides (DAOs) and d-xylose represented intestinal barrier function and absorption function, respectively, and correlated with the extent of damage (P enteritis, thus obtaining a relatively objective evaluation of intestinal tract injury based on clinical performance and laboratory examination. The method of assessment of the degree of intestinal tract injury after abdominal irradiation could be beneficial in the development of novel and effective therapeutic strategies for acute radiation enteritis.

  9. [Treatment of extensive acute radiation burn and its complications].

    Science.gov (United States)

    Li, Ye-yang; Wang, Jin-lun; Li, Gang; Lin, Wei-hua; Liang, Min; Huang, Jun; Sun, Jing-en

    2013-06-01

    This article reports the treatment of a patient suffered from acute radiation burn covering 41% TBSA, with deep partial-thickness and full-thickness injury, produced by exposure to a large-scale industrial electron accelerator. An open wound began to appear and enlarged gradually 10 weeks after the exposure. Serious wound infection with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, pneumonia, respiratory failure, systemic inflammatory response syndrome, nephropathy and hypoproteinemia developed successively since 3 weeks after the wound formation. Skin grafts failed to survive, resulting in enlargement of the wound. After being treated with proper measures, including parenteral nutrition, respiratory support with a ventilator, appropriate antibiotics, steroid administration for nephropathy, deep debridement for wounds followed by skin grafting, the patient was cured and discharged after undergoing 15 operations in 500 days. The clinical condition of an extensive acute radiation burn is complicated. We should pay close attention to the changes in functions of organs, and strengthen the therapeutic strategies to support the function of organs to reduce the incidence of systemic complications. The control of the infection and the timely and effective repair of the wound are still the key points of the treatment of an extensive local radiation injury.

  10. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

    Science.gov (United States)

    Popov, Dmitri

    Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

  11. Antiradiation Antitoxin IgG : Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava

    Introduction: High doses of radiation induce apoptotic necrosis of radio-sensitive cells. Mild doses of radiation induce apoptosis or controlled programmed death of radio-sensitive cells with-out development of inflammation and formation of Radiation Toxins. Cell apoptotic necrosis initiates Radiation Toxins (RT)formation. Radiation Toxins play an important role as a trig-ger mechanism for inflammation development and cell lysis. If an immunotherapy approach to treatment of the acute radiation syndromes (ARS) were to be developed, a consideration could be given to neutralization of radiation toxins (Specific Radiation Determinants-SRD) by specific antiradiation antibodies. Therapeutic neutralization effects of the blocking anti-radiation antibodies on the circulated RT had been studied. Radiation Toxins were isolated from the central lymph of irradiated animals with Cerebrovascular(Cv ARS),Cardiovascular (Cr ARS),Gastrointestinal(Gi ARS) and Haemopoietic (Hp ARS) forms of ARS. To accomplish this objective, irradiated animals were injected with a preparation of anti-radiation immunoglobulin G (IgG) obtained from hyperimmune donors. Radiation-induced toxins that we call Specific Radiation Determinants (SRD) possess toxic (neurotoxic, haemotoxic) characteristics as well as specific antigenic properties. Depending on direct physiochemical radiation damage, they can induce development of many of the pathological processes associated with ARS. We have tested several specific hyperimmune IgG preparations against these radiation toxins and ob-served that their toxic properties were neutralized by the specific antiradiation IgGs. Material and Methods: A scheme of experiments was following: 1.Isolation of radiation toxins (RT) from the central lymph of irradiated animals with different form of ARS. 2.Transformation of a toxic form of the RT to a toxoid form of the RT. 3.Immunization of radiation naive animals. Four groups of rabbits were inoculated with a toxoid form of SRD

  12. Radiation-induced hypopituitarism in children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Mehrdad Mirouliaei

    2013-01-01

    Full Text Available Background: Acute Lymphoblastic Leukemia (ALL is the most common malignancy among children for whom radiotherapy and chemotherapy are used for treatment. When hypothalamus-pituitary axis is exposed to radiotherapy, children′s hormone level and quality of life are influenced. The aim of this study is to determine late effects of radiotherapy on hormonal level in these patients. Materials and Methods: In this study 27 children with ALL, who have been referred to Shahid Ramezanzadeh Radiation Oncology Center in Yazd-Iran and received 18-24 Gy whole brain radiation with Cobalt 60 or 9 MV linear accelerator, were assessed. These patient′s basic weight, height and hormonal levels were measured before radiotherapy and also after different periods of time. Results: GHD (growth hormone deficiency after clonidine stimulation test was observed in 44% ( n=12 and that in 50% of them ( n=6, less than 1 year, had been passed from their radiation therapy. None of these patients demonstrated hormone deficiency in other axes. Conclusions: This study showed that even application of a 18-24 Gy radiation dose might influence growth hormone levels; therefore, we recommend reduction of radiotherapy dose in such patients whenever possible.

  13. Chlamydial Pneumonitis: A Creepy Neonatal Disease

    Directory of Open Access Journals (Sweden)

    Kam Lun Hon

    2013-01-01

    Full Text Available We present a case of neonatal chlamydial pneumonitis to illustrate that a high index of suspicion is necessary to make the diagnosis so that treatment can be promptly instituted. The child was afebrile and the only symptom was a cough. The respiratory equations are calculated to understand the respiratory physiology. There was no overt abnormality with ventilation, oxygenation, compliance, resistance, or ventilation-perfusion mismatch despite radiographic abnormality. The literature is searched to review if treatment with a systemic macrolide antibiotic is needed in an otherwise asymptomatic neonate with chlamydial pneumonitis.

  14. Serum protein concentrations in calves with experimentally induced pneumonic pasteurellosis

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    Fagliari J.J.

    2003-01-01

    Full Text Available Ten healthy 2 to 4-week-old Holstein calves were randomly allotted into control and infected groups. Control calves (n=5 were inoculated intrabronchially with 5ml of Dulbecco's phosphate-buffered saline solution (DPBSS. Infected calves (n=5 were inoculated intrabronchially with 5x10(9 log-phase Mannheimia haemolytica organisms suspended in 5ml of DPBSS. Blood samples were obtained 15 minutes before and one, two, four and six hours after inoculation. Serum protein concentrations were determined by means of sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Serum concentrations of proteins with molecular weights of 125,000 D (ceruloplasmin, 60,000 D (a 1-antitrypsin, 45,000 D (haptoglobin, and 40,000 D (acid glycoprotein were significantly increased in calves with pneumonic pasteurellosis, compared with concentrations in control calves. Results indicate that acute phase proteins increase more rapidly after the onset of inflammation than previously thought. Measurement of serum protein concentrations may be useful in monitoring the progression of the induced pneumonic pasteurellosis in calves.

  15. A case of acutely developed delayed radiation myelopathy

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Shintaro; Amari, Masakuni [Geriatrics Research Inst., Maebashi (Japan). Hospital; Fukuda, Toshio; Okamoto, Koichi [Gunma Univ., Maebashi (Japan). School of Medicine

    2002-08-01

    A 66-year-old man with a history of hypertension received radiation therapy on his neck at age 61 because of laryngeal cancer (T1bN0M0). Five years after the radiation, he acutely developed dysuria, tetraparesis and dissociated sensory disturbances below bilateral Th4 level. T2 weighted MRI showed a high signal lesion affecting the central area of the spinal cord extending from C1 to C7. On the second clinical day, he developed respiratory arrest and was ventilated. The cerebrospinal fluid contained 20/mm{sup 3} (monocyte 15, neutorophil 5) white cells; protein was 52.5 mg/dl; IgG index 0.54; Q albumin was 9.6; tests for oligoclonal band and myelin basic protein were negative; a culture yielded no microorganism. He was treated with steroids and supportive measures without improvement, and died of a sudden cardiac arrest on the 8th clinical day. postmortem examination confirmed conspicuous focal spongy changes with many axonal swellings, especially in the posterior and lateral columns at cervical and Th1 levels. The pathological findings were considered to be compatible with those of delayed radiation myelopathy (DRM). In the anterior horn of the cervical cord there were lesions of diffuse racification and the proliferation of small vessels. There were no findings of hyaline vascular changes, infarction or metastasis of laryngeal cancer at the spinal cord. It is considered that hyperintensity of signals on T2-weighted may originate from racification and proliferation of small vessels in the gray matter, and these pathological changes would be intimately associated with the severe neurologic morbidity of this patient. Acute development of neurological findings and the pathological changes in the gray matter of the spinal cord are rare manifestations of DRM. (author)

  16. Differences and radiation pneumonitis prediction of lung dosimetric parameters based on three normal lung definitions in 3DCRT treatment planning%3DCRT计划中不同肺定义对肺癌放疗的影响

    Institute of Scientific and Technical Information of China (English)

    王谨; 包勇; 庄婷婷; 张黎; 何智纯; 徐裕金; 马红莲; 胡晓; 周琦超

    2014-01-01

    Objective To compare lung dose-volume histogram (DVH) parameters based on commonly used normal lung definitions,i.e.,lungs-gross tumor volume (GTV),lungs-clinical target volume (CTV),and lungs-planning target volume (PTV),in three-dimensional conformal radiotherapy (3 DCRT) and to determine to what extent they differ in predicting radiation pneumonitis (RP).Methods A total of 147 non-small cell lung cancer patients treated with concurrent chemotherapy and 3DCRT from 2006 to 2010 were collected.RP was diagnosed according to RTOG criteria.Lung DVHs were generated with exclusion of GTV,CTV,or PTV.Independent-samples t test was used to compare DVH parameters based on different normal lung definitions,and the predictive values of these parameters for RP were evaluated with the receiver operating characteristic (ROC) curve.Results There were significant differences in minimum lethal dose (MLD) between lungs-GTV and lungs-CTV/lungs-PTV ((1.16 ± 0.96) Gy vs.(3.45 ± 1.43) Gy).The biggest difference in MLD for the same patient based on different definitions was 8.73 Gy.MLD based on lungs-GTV had a better predictive value for grades ≥2 and ≥3 RP than MLD based on lungs-CTV and lungs-PTV,with larger areas under the ROC curve (lungs-GTV ∶ area =0.614,P=0.024;area =0.678,P=0.056;lungs-CTV∶area =0.556,P=0.269;area =0.602,P=0.226 ; lungs-PTV ∶ area =0.551,P =0.317 ; area =0.616,P =0.167).We drew a similar conclusion when analyzing lung V5-V50.Conclusions There are significant differences between DVH parameters based on various normal lung definitions,which cannot be neglected in the clinical setting.DVH parameters based on lungs-GTV may be the most accurate in predicting RP.%目的 探讨3DCRT计划中双肺-GTV、CTV、PTV三种定义下正常肺DVH参数差异及对RP的预测价值.方法 对2006-2010年间行3DCRT的147例NSCLC患者分别定义双肺-GTV、CTV、PTV正常肺并收集相关DVH剂量学信息,比较参数值差异及其对RP的预测价值.剂量

  17. Vaccination against bubonic and pneumonic plague.

    Science.gov (United States)

    Titball, R W; Williamson, E D

    2001-07-20

    Yersinia pestis is the etiological agent of bubonic and pneumonic plague, diseases which have caused over 200 milllion human deaths in the past. Plague still occurs throughout the world today, though for reasons that are not fully understood pandemics of disease do not develop from these outbreaks. Antibiotic treatment of bubonic plague is usually effective, but pneumonic plague is difficult to treat and even with antibiotic therapy death often results. A killed whole cell plague vaccine has been used in the past, but recent studies in animals have shown that this vaccine offers poor protection against pneumonic disease. A live attenuated vaccine is also available. Whilst this vaccine is effective, it retains some virulence and in most countries it is not considered to be suitable for use in humans. We review here work to develop improved sub-unit and live attenuated vaccines against plague. A sub-unit vaccine based on the F1- and V-antigens is highly effective against both bubonic and pneumonic plague, when tested in animal models of disease. This vaccine has been used to explore the utility of different intranasal and oral delivery systems, based on the microencapsulation or Salmonella delivery of sub-units.

  18. Bubonic and pneumonic plague - Uganda, 2006.

    Science.gov (United States)

    2009-07-24

    Plague is a life-threatening fleaborne disease caused by the bacterium Yersinia pestis. The most common clinical form is bubonic plague, which is characterized by high fever and regional lymphadenitis. Without treatment, infection can spread from lymph nodes to the lungs, resulting in pneumonic plague and the potential for person-to-person transmission through respiratory droplets. In November 2006, the Uganda Ministry of Health received reports of an increase in bubonic plague cases and a possible outbreak of pneumonic plague among residents in the Arua and Nebbi districts. In response, the Uganda Ministry of Health and CDC conducted a joint investigation in the two districts during November 28-December 30, 2006. Overall, 127 clinical plague cases were identified, along with evidence of a focal pneumonic outbreak in Nebbi District. Median age of the patients was 14 years (range: 2 weeks-65 years); 65 (51%) were female. Twenty-eight (22%) of the 127 patients died. Among the 102 patients with documented symptoms, 90 (88%) had bubonic plague, and 12 (12%) had pneumonic plague. The results of this investigation underscore the need to 1) continue efforts to educate residents of rural Uganda regarding the source, signs, and symptoms of plague and the life-saving importance of seeking treatment; 2) strengthen plague surveillance and diagnostic capabilities; and 3) improve emergency response and vector-control capacity, especially in remote regions of the country.

  19. Treatment and prevention of acute radiation dermatitis;Traitement et prevention des radiodermites aigues

    Energy Technology Data Exchange (ETDEWEB)

    Benomar, S.; Hassam, B. [Service de dermatologie, CHU Ibn-Sina, universite Mohamed-V, Rabat (Morocco); Boutayeb, S.; Errihani, H. [Service de d' oncologie medicale, Institut national d' oncologie, Universite Mohamed-V, Rabat (Morocco); Lalya, I.; El Gueddari, B.K. [Service de radiotherapie, Institut national d' oncologie, universite Mohamed-V, Rabat (Morocco)

    2010-06-15

    Acute radiation dermatitis is a common side-effect of radiotherapy which often necessitates interruption of the therapy. Currently, there is no general consensus about its prevention or about the treatment of choice. The goal of this work was to focus on optimal methods to prevent and manage acute skin reactions related to radiation therapy and to determine if there are specific topical or oral agents for the prevention of this acute skin reaction. The prevention and the early treatment are the two focus points of the management of the acute radiation dermatitis. (authors)

  20. Hypersensitivity pneumonitis caused by the broom grass (Calluna vulgaris

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    Yusuf Aydemir

    2015-01-01

    Full Text Available Hypersensitivity pneumonitis (HP, is an inflammatory disease that represents one possible response of the interstitial and parenchymal tissue to the intensive and repeated inhalation of organic dusts or reactive chemicals substances. In this case report, for the first time in the literature as we know, acute hypersensitivity pneumonitis in a patient who working in broom grass manufacturing were presented. Broom manufacturer employee 35 years old female patient was admitted with dyspnea, fever and cough, beginning the three months before. Physical examination, there were bilateral basal crackles. On Thorax CT bilateral diffuse ground-glass opacity and mosaic perfusion were observed. Patient was hospitalized, IV prednisolone therapy was started. Almost complete clinical improvement was achieved. We would like to emphasize that detailed occupational history should be questioned; because; diagnosis of acute HP, due to the mixing with the viral infection or atypical pneumonia, easily skipped.

  1. Cladosporium species-related hypersensitivity pneumonitis in household environments.

    Science.gov (United States)

    Chiba, Shigeki; Okada, Shinji; Suzuki, Yasuko; Watanuki, Zenta; Mitsuishi, Yoichiro; Igusa, Ryotaro; Sekii, Takehiko; Uchiyama, Bine

    2009-01-01

    Home-related chronic hypersensitivity pneumonitis (HP) is sometimes difficult to discriminate because patients do not have an obvious history of antigen exposure. We report two HP cases which developed in an office area and in a home: a 47-year-old woman with acute-onset HP and a 72-year-old woman with chronic HP followed up as idiopathic pulmonary fibrosis following isolation of Cladosporium cladosporioides and Cladosporium herbarum, respectively. Lymphocyte stimulating activity and antibody titer to these fungi were increased in these patients. Since Cladosporium spp. and several other fungi are present ubiquitously in our living environment, it is difficult to eliminate the antigen from the patients' environment to control the disease. Cladosporium spp. can be key antigens in inducing chronic HP in the home environment.

  2. Acute myelogenous leukemia following chemotherapy and radiation for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Aso, Teijiro; Hirota, Yuichi; Kondou, Seiji; Matsumoto, Isao; Matsuzaka, Toshimitsu; Iwashita, Akinori

    1989-03-01

    In August 1982, a 44-year-old man was diagnosed as having rectal cancer, histologically diagnosed as well differentiated adenocarcinoma, and abdominoperineal resection and colostomy were performed. Postoperatively, he received chemotherapy with mitomycin C up to a total dose of 100 mg. In September 1986, lung metastasis occurred and he was treated with a combination chemotherapy consisting of cisplatin, pirarubicin and 5-fluorouracil. In the following year, radiation treatment (total: 6900 rad) was given for a recurrent pelvic lesion. Peripheral blood on April 30, 1988, showed anemia, thrombocytopenia and appearance of myeloblasts, and a diagnosis of acute myelogenous leukemia (FAB: M1) was made. Combination chemotherapy (including aclarubicin, vincristine, behenoyl ara-C, daunorubicin, 6-mercaptopurine, cytarabine, etoposide and prednisolone) failed to induce remission and the patient died in June 1988. This case was thought to be one of secondary leukemia occurring after chemotherapy and radiation treatment for rectal cancer. This case clearly indicates the need for a careful follow-up of long-term survivors who have received cancer therapy. (author).

  3. Impact of diabetes mellitus on clinicopathological factors and relation with radiation pneumonitis in 332 patients with lung cancer%332例肺癌临床病理因素及放射性肺炎与糖尿病的相关性分析

    Institute of Scientific and Technical Information of China (English)

    周海芝; 曹科; 曹培国; 蒋文婷

    2013-01-01

    Objective: To explore the relation between diabetes mellitus and clinicopathological factors and the incidence of radiation pneumonitis in patients with non-small cell lung cancer. Methods: The data of 332 patients with non-small cell lung cancer, who were admitted to the Department of Oncology of Third Xiangya Hospital of Central South University between January 2007 and August 2009, were collected retrospectively. The patients were divided into a diabetes mellitus (DM) group (n=45) and a non-diabetes mellitus (NDM) group (n=287). The clinicopathological factors were compared between the two groups. The patients who received radiotherapy were further divided into a diabetes mellitus (DMR) group (n=33) and a non-diabetes mellitus group (NDMR) group(n=287), and the incidence of radiation pneumonitis was compared. Results: A total of 45 patients (13.55%)developed diabetes mellitus. There was significant difference in the body-weight, age and hypertension (P0.05). No significant difference in the irradiation area was found between the DM group and the NDM group(P>0.05). The incidence of radiation pneumonitis in the DMR group was 42.42%(14 out of 33), while 21.31%(39 out of 183) in the NDMR group, with significant difference in the incidence of radiation pneumonitis between the DMR group and the NDMR group(P<0.05). The risk value in the DMR group was 2.721 folds (95%CI, 1.253-5.910) that in the NDMR group in patients with non-small cell lung cancer companied with diabetes mellitus. Conclusion: Diabetes mellitus is the risk factor of radiation pneumonitis for patients with non-small cell lung cancer who receive radiotherapy.%目的:探讨糖尿病与非小细胞肺癌(non small cell lung cancer,NSCLC)临床病理因素的关系及对放射性肺炎发生率的影响.方法:回顾性分析2007年1月至2009年8月入住中南大学湘雅三医院肿瘤科的332例NSCLC患者的临床资料,将其分为糖尿病(diabetes mellitus,DM)组(n=45)

  4. The role of MRI in the diagnosis of acute radiation reaction in breast cancer patient

    Science.gov (United States)

    Startseva, Zh A.; Musabaeva, L. I.; Usova, AV; Frolova, I. G.; Simonov, K. A.; Velikaya, V. V.

    2016-02-01

    A clinical case with acute radiation reaction of the left breast after organ-preserving surgery with 10 Gy IORT (24.8 Gy) conventional radiation therapy has been presented. Comprehensive MRI examination showed signs of radiation- induced damage to skin, soft tissues and vessels of the residual breast.

  5. Simultaneous interstitial pneumonitis and cardiomyopathy induced by venlafaxine

    Directory of Open Access Journals (Sweden)

    Pedro Gonçalo Ferreira

    2014-06-01

    Full Text Available Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used as an antidepressant. Interindividual variability and herb-drug interactions can lead to drug-induced toxicity. We report the case of a 35-year-old female patient diagnosed with synchronous pneumonitis and acute cardiomyopathy attributed to venlafaxine. The patient sought medical attention due to dyspnea and dry cough that started three months after initiating treatment with venlafaxine for depression. The patient was concomitantly taking Centella asiatica and Fucus vesiculosus as phytotherapeutic agents. Chest CT angiography and chest X-ray revealed parenchymal lung disease (diffuse micronodules and focal ground-glass opacities and simultaneous dilated cardiomyopathy. Ecocardiography revealed a left ventricular ejection fraction (LVEF of 21%. A thorough investigation was carried out, including BAL, imaging studies, autoimmune testing, right heart catheterization, and myocardial biopsy. After excluding other etiologies and applying the Naranjo Adverse Drug Reaction Probability Scale, a diagnosis of synchronous pneumonitis/cardiomyopathy associated with venlafaxine was assumed. The herbal supplements taken by the patient have a known potential to inhibit cytochrome P450 enzyme complex, which is responsible for the metabolization of venlafaxine. After venlafaxine discontinuation, there was rapid improvement, with regression of the radiological abnormalities and normalization of the LVEF. This was an important case of drug-induced cardiopulmonary toxicity. The circumstantial intake of inhibitors of the CYP2D6 isoenzyme and the presence of a CYP2D6 slow metabolism phenotype might have resulted in the toxic accumulation of venlafaxine and the subsequent clinical manifestations. Here, we also discuss why macrophage-dominant phospholipidosis was the most likely mechanism of toxicity in this case.

  6. [Nonspecific interstitial pneumonitis: a clinicopathologic entity, histologic pattern or unclassified group of heterogeneous interstitial pneumonitis?].

    Science.gov (United States)

    Morais, António; Moura, M Conceição Souto; Cruz, M Rosa; Gomes, Isabel

    2004-01-01

    Nonspecific interstitial pneumonitis (NSIP) initially described by Katzenstein and Fiorelli in 1994, seems to be a distinct clinicopathologic entity among idiopathic interstitial pneumonitis (IIP). Besides different histologic features from other IIP, NSIP is characterized by a better long-term outcome, associated with a better steroids responsiveness than idiopathic pulmonar fibrosis (IPF), where usually were included. Thus, differentiating NSIP from other IIP, namely IPF is very significant, since it has important therapeutic and prognostic implications. NSIP encloses different pathologies, namely those with inflammatory predominance (cellular subtype) or fibrous predominance (fibrosing subtype). NSIP is reviewed and discussed by the authors, after two clinical cases description.

  7. Anti-radiation vaccine: Immunologically-based Prophylaxis of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight

    Science.gov (United States)

    Popov, Dmitri; Maliev, Vecheslav; Jones, Jeffrey; Casey, Rachael C.

    2007-01-01

    Protecting crew from ionizing radiation is a key life sciences problem for long-duration space missions. The three major sources/types of radiation are found in space: galactic cosmic rays, trapped Van Allen belt radiation, and solar particle events. All present varying degrees of hazard to crews; however, exposure to high doses of any of these types of radiation ultimately induce both acute and long-term biological effects. High doses of space radiation can lead to the development of toxicity associated with the acute radiation syndrome (ARS) which could have significant mission impact, and even render the crew incapable of performing flight duties. The creation of efficient radiation protection technologies is considered an important target in space radiobiology, immunology, biochemistry and pharmacology. Two major mechanisms of cellular, organelle, and molecular destruction as a result of radiation exposure have been identified: 1) damage induced directly by incident radiation on the macromolecules they encounter and 2) radiolysis of water and generation of secondary free radicals and reactive oxygen species (ROS), which induce chemical bond breakage, molecular substitutions, and damage to biological molecules and membranes. Free-radical scavengers and antioxidants, which neutralize the damaging activities of ROS, are effective in reducing the impact of small to moderate doses of radiation. In the case of high doses of radiation, antioxidants alone may be inadequate as a radioprotective therapy. However, it remains a valuable component of a more holistic strategy of prophylaxis and therapy. High doses of radiation directly damage biological molecules and modify chemical bond, resulting in the main pathological processes that drive the development of acute radiation syndromes (ARS). Which of two types of radiation-induced cellular lethality that ultimately develops, apoptosis or necrosis, depends on the spectrum of incident radiation, dose, dose rate, and

  8. Study on hypersensitivity pneumonitis. Scintigraphic findings in three cases

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Tadashige; Hirayama, Jiro; Kanai, Hisakata (Shinshu Univ., Matsumoto, Nagano (Japan). Faculty of Medicine)

    1982-11-01

    Three cases with hypersensitivity pneumonitis were studied with Tl-201 scintigraphy, perfusion lung scan and other clinical findings. Major symptoms and signs were fever and cough in 3 cases, exertional dyspnea in 2, sputum in 1 and moist rales in 3. Laboratory data showed elevated ESR, hyper ..gamma..-globulinemia in 3 cases, leukocytosis in 2, eosinophilia in 3, positive CRP in 2 and positive RA test in 1. Chest x-ray film revealed diffuse scattered reticulonodular shadows in 3 cases and patchy ones in 2. Abnormalities in the pulmonary function tests were decreased vital capacity and Pa sub(o2) in 3 cases, increased residual volume and decreased diffusion capacity in 2, decreased V50 and V25 in flow volume curve in 1. Precipitating antibodies against Sitophilus granarius, Thermoactinomyces vulgaris, Micropolyspola faeni, Aspergillus fumigatus and budgerigar serum were detected. Tl-201 scintigram showed diffuse marked uptake of Tl-201 in both lungs of 2 cases at acute stage and moderate in 2 cases in remission when abnormal shadows on chest x-ray film had been disappeared. Two cases in remission showed slight positive or negative results, but in 1 case moderate uptake was yet observed after 11 months. Positive visualization of right ventricle was demonstrated in 2 cases. Perfusion lung scintigram showed decreased perfusion in 3 cases. Each of 2 cases in acute stage and in remission showed slightly decreased perfusion and one case in admission showed a moderate decrease and still showed a slight decrease after 9 months.

  9. Radiation-induced apoptosis in relation to acute impairment of rat salivary gland function

    NARCIS (Netherlands)

    Paardekooper, GMRM; Cammelli, S; Zeilstra, LJW; Coppes, RP; Konings, AWT

    1998-01-01

    Purpose: To find an answer to the question: Are the acute radiation effects on salivary gland function, as seen in earlier studies, causally related to radiation-induced apoptosis? Materials and methods: Rat parotid and submandibular glands were X-irradiated with doses up to 25 Gy and morphological

  10. Does VMAT for treatment of NSCLC patients increase the risk of pneumonitis compared to IMRT ? - a planning study

    DEFF Research Database (Denmark)

    Bertelsen, Anders; Hansen, Olfred; Brink, Carsten

    2012-01-01

    Volumetric modulated arc therapy (VMAT) for treatment of non-small cell lung cancer (NSCLC) patients potentially changes the risk of radiation-induced pneumonitis (RP) compared to intensity modulated radiation therapy (IMRT) if the dose to the healthy lung is changed significantly. In this study,......, clinical IMRT plans were used as starting point for VMAT optimization and differences in risk estimates of RP between the two plan types were evaluated....

  11. Pneumonic Plague: The Darker Side of Yersinia pestis.

    Science.gov (United States)

    Pechous, Roger D; Sivaraman, Vijay; Stasulli, Nikolas M; Goldman, William E

    2016-03-01

    Inhalation of the bacterium Yersinia pestis results in primary pneumonic plague. Pneumonic plague is the most severe manifestation of plague, with mortality rates approaching 100% in the absence of treatment. Its rapid disease progression, lethality, and ability to be transmitted via aerosol have compounded fears of the intentional release of Y. pestis as a biological weapon. Importantly, recent epidemics of plague have highlighted a significant role for pneumonic plague during outbreaks of Y. pestis infections. In this review we describe the characteristics of pneumonic plague, focusing on its disease progression and pathogenesis. The rapid time-course, severity, and difficulty of treating pneumonic plague highlight how differences in the route of disease transmission can enhance the lethality of an already deadly pathogen. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Principles of medical rehabilitation of survivors of acute radiation sickness induced by gamma and beta and gumma and neutron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nedejina, N.M.; Galstian, I.A.; Savitsky, A.A.; Sachkov, A.V.; Rtisheva, J.N.; Uvatcheva, I.V.; Filin, S.V. [State Research Center of Russia, Moscow (Russian Federation). Inst. of Biophysics

    2000-05-01

    The purpose of this study is to reveal the principles of medical rehabilitation different degree acute radiation syndrome (ARS) survivors, who exposed {gamma}{beta}- and {gamma}{eta}-irradiation in different radiation accidents. The main reasons of working disability in the late consequences of ARS period are consequences of local radiation injures (LRI) and joining somatic diseases. Its revealing and treatment considerably improves quality of life of the patients. The heaviest consequence of LRI of a skin at {gamma}{beta}- radiation exposure is the development of late radiation ulcers and radiation fibrosis, which require repeated plastic surgery. LRI at {gamma}{eta}-radiation exposure differ by the greater depth of destruction of a underlying tissues and similar defects require the early amputations. Last 10 years microsurgery methods of plastic surgery allow to save more large segments of extremities and to decrease expression of the late consequences (radiation fibrosis and late radiation ulcers) LRI severe and extremely severe degrees. Medical rehabilitation of radiation cataract (development at doses more than 2.0 Gy) includes its extraction and artificial lens implantation, if acuity of vision is considerably decreased. Changes of peripheral blood, observed at the period of the long consequences, as a rule, different, moderate, transient and not requiring treatment. Only one ARS survivor dead from chronic myeloid leukemia. Thyroid nodes, not requiring operative intervention, are found out in Chernobyl survivors. Within the time course the concurrent somatic disease become the major importance for patients disability growth, which concurrent diseases seem to be unrelated to radiation dose and their structure does not differ from that found in general public of Russia. The rehabilitation of the persons who have transferred ARS as a result of radiating failure, should be directed on restoration of functions critical for ionizing of radiation of bodies and

  13. HEPATITIS AND PNEUMONITIS DURIN ADALIMUMAB THERAPY IN CROHN? DISEASE: mind the histoplasmosis!

    Directory of Open Access Journals (Sweden)

    Bruno do Valle PINHEIRO

    2014-03-01

    Full Text Available Context Tumor necrosis factor-alpha (TNF-α inhibitor therapy plays a pivotal role in the management of moderate to severe inflammatory bowel disease. Because of the role of TNF-α in the host defenses, anti-TNF therapy has been associated with an increase the risks of granulomatous infections. Objective To report the first case of adalimumab-associated invasive histoplasmosis presenting as an acute hepatitis-like syndrome and febrile pneumonitis in a patient with Crohn’s disease. Method Case report of a patient with progressive histoplasmosis confirmed by percutaneous fine needle aspiration biopsy lung and urine Histoplasma antigen. Results We present the case of a young man with CD who developed pneumonia and acute hepatitis-like features caused by Histoplasma capsulatum infection during adalimumab therapy. To the best of our knowledge, this acute hepatitis-like manifestation has never been reported as a presentation of the histoplasmosis in patients with Crohn’s disease. Conclusions This case underscores the potential risk for serious infection that may arise in this setting and should alert clinicians to the need to consider the histoplasmosis diagnosis in patients presenting with acute hepatitis-like syndrome associated with prolonged febrile illness or pneumonitis during therapy with anti-TNF-α antibodies.

  14. Mathematical Models of Human Hematopoiesis Following Acute Radiation Exposure

    Science.gov (United States)

    2014-05-01

    the model predicts. Radiation dose from skin contamination can result in cutaneous injury leading to systemic responses and may im- pact the observed...medical and performance consequences from radiation and combined injuries , thereby enhancing our understanding of the potential impact of a nuclear...subsequently. In addition to the insight gained from combined injury modeling, the models of hematopoiesis and radiation alone provide clini- cally

  15. The acute radiation syndrome: A study of ten cases and a review of the problem

    Energy Technology Data Exchange (ETDEWEB)

    Hempelmann, L.H.; Lisco, H.

    1950-03-17

    In this report ten cases of acute radiation syndrome are described resulting from two accidents occurring at the Los Alamos Scientific Laboratory of unique nature involving fissionable material. These cases are described in considerable detail. The report comprises ten sections. This volume, part II of the report, is comprised of sections entitled: (1) the Biological Basis for the Clinical Response seen in the Acute radiation Syndrome, (2) Clinical Signs and Symptoms, (3) Discussion of Hematological Findings, (4) Chemistry of the Blood and Urine, (5) Discussion of Pathological Findings, and (6) Reconsiderations of the Calculated Radiation Doses in Terms of the Observed Biological Response of the Patients. This report was prepared primarily for the clinician who is interested in radiation injuries and therefore emphasis has been placed on the correlation of clinical and pathological changes with the type of cytogenetic change known to be produced by ionizing radiation.

  16. Rays Sting: The Acute Cellular Effects of Ionizing Radiation Exposure.

    Science.gov (United States)

    Franco, A; Ciccarelli, M; Sorriento, D; Napolitano, L; Fiordelisi, A; Trimarco, B; Durante, M; Iaccarino, G

    2016-05-01

    High-precision radiation therapy is a clinical approach that uses the targeted delivery of ionizing radiation, and the subsequent formation of reactive oxygen species (ROS) in high proliferative, radiation sensitive cancers. In particular, in thoracic cancer ratdiation treatments, can not avoid a certain amount of cardiac toxicity. Given the low proliferative rate of cardiac myocytes, research has looked at the effect of radiation on endothelial cells and consequent coronary heart disease as the mechanism of ratdiation induced cardiotoxicity. In fact, little is known concerning the direct effect of radiation on mitochondria dynamis in cardiomyocyte. The main effect of ionizing radiation is the production of ROS and recent works have uncovered that they directly participates to pivotal cell function like mitochondrial quality control. In particular ROS seems to act as check point within the cell to promote either mitochondrial biogenesis and survival or mitochondrial damage and apoptosis. Thus, it appears evident that the functional state of the cell, as well as the expression patterns of molecules involved in mitochondrial metabolism may differently modulate mitochondrial fate in response to radiation induced ROS responses. Different molecules have been described to localize to mitochondria and regulate ROS production in response to stress, in particular GRK2. In this review we will discuss the evidences on the cardiac toxicity induced by X ray radiation on cardiomyocytes with emphasis on the role played by mitochondria dynamism.

  17. Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis.

    Science.gov (United States)

    Kolbe, Scott C; van der Walt, Anneke; Butzkueven, Helmut; Klistorner, Alexander; Egan, Gary F; Kilpatrick, Trevor J

    2016-01-01

    Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of -2.6% per annum (control = -0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = -0.428, p = 0.009; MD: R = -0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage.

  18. Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis

    Directory of Open Access Journals (Sweden)

    Scott C. Kolbe

    2016-01-01

    Full Text Available Previous studies have reported diffusion tensor imaging (DTI changes within the optic radiations of patients after optic neuritis (ON. We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1. We measured DTI parameters [fractional anisotropy (FA, axial diffusivity (AD, radial diffusivity (RD, and mean diffusivity (MD] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of −2.6% per annum (control = −0.51%; p=0.006. Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R=0.450, p=0.006; RD: R=-0.428, p=0.009; MD: R=-0.365, p=0.029. In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R=0.489, p=0.039. In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage.

  19. Acute Radiation Hypotension in the Rabbit: a Model for the Human Radiation Shock Syndrome.

    Science.gov (United States)

    Makale, Milan Theodore

    This study has shown that total body irradiation (TBI) of immature (40 to 100 day old) rabbits leads to an acute fall in mean arterial pressure (MAP) 30 to 90 minutes after exposure, which takes no more than about three minutes, and often results in pressures which are less than 50% of the lowest pre-exposure MAP. This is termed acute cardiovascular collapse (ACC). ACC is often accompanied by ECG T-wave elevation, a sharp rise in ear temperature, labored breathing, pupillary constriction, bladder emptying, and loss of abdominal muscle tone. About 73% of 40 to 100 day rabbits exhibit ACC; the others and most older rabbits display gradual pressure reductions (deliberate hypotension) which may be profound, and which may be accompanied by the same changes associated with ACC. ACC and deliberate hypotension occurred in rabbits cannulated in the dorsal aorta, and in non-operated animals. The decline in MAP for all 40 to 100 day cannulated rabbits (deliberate and ACC responders) is 55.4%. The experiments described below only involved 40 to 100 day cannulated TBI rabbits. Heart region irradiation resulted in an average MAP decline of 29.1%, with 1/15 rabbits showing ACC. Heart shielding during TBI reduced the decline in MAP to 19%, with 1/10 rabbits experiencing ACC. These results imply that the heart region, which includes the heart, part of the lungs, neural receptors, roots of the systemic vessels, and the blood, is a sensitive target. Bilateral vagotomy reduced the decline in MAP to 24.9%, and abolished ACC. Atropine (6 mg/kg) reduced the frequency of ACC to 26%, and the decline in MAP to 41.4%. In 11/13 rabbits the voltage generated by left vagal transmission rose after TBI. The vagi appear to participate in radiation hypotension. Heart shielding together with bilateral vagotomy reduced the decline in MAP to only 9.9%, with no ACC responders. The mean right ventricular pressure (MRVP) rose after TBI in 8/10 rabbits. In animals which displayed either ACC or steep

  20. Pneumonic Plague Outbreak, Northern Madagascar, 2011

    Science.gov (United States)

    Richard, Vincent; Herindrainy, Perlinot; Soanandrasana, Rahelinirina; Ratsitoharina, Maherisoa; Rakotomanana, Fanjasoa; Andrianalimanana, Samuel; Scholz, Holger C.; Rajerison, Minoarisoa

    2015-01-01

    Yersinia pestis, the causative agent of plague, is endemic to Madagascar, particularly to the central highlands. Although plague has not been previously reported in northern Madagascar, an outbreak of pneumonic plague occurred in this remote area in 2011. Over a 27-day period, 17 suspected, 2 presumptive, and 3 confirmed human cases were identified, and all 15 untreated 20 patients died. Molecular typing of Y. pestis isolated from 2 survivors and 5 Rattus rattus rat samples identified the Madagascar-specific 1.ORI3-k single-nucleotide polymorphism genotype and 4 clustered regularly interspaced short palindromic repeat patterns. This outbreak had a case-fatality rate of 100% for nontreated patients. The Y. pestis 1.ORI3-k single-nucleotide polymorphism genotype might cause larger epidemics. Multidrug-resistant strains and persistence of the pathogen in natural foci near human settlements pose severe risks to populations in plague-endemic regions and require outbreak response strategies. PMID:25530466

  1. Countermeasures for Space Radiation Induced Malignancies and Acute Biological Effects

    Science.gov (United States)

    Kennedy, Ann

    The hypothesis being evaluated in this research program is that control of radiation induced oxidative stress will reduce the risk of radiation induced adverse biological effects occurring as a result of exposure to the types of radiation encountered during space travel. As part of this grant work, we have evaluated the protective effects of several antioxidants and dietary supplements and observed that a mixture of antioxidants (AOX), containing L-selenomethionine, N-acetyl cysteine (NAC), ascorbic acid, vitamin E succinate, and alpha-lipoic acid, is highly effective at reducing space radiation induced oxidative stress in both in vivo and in vitro systems, space radiation induced cytotoxicity and malignant transformation in vitro [1-7]. In studies designed to determine whether the AOX formulation could affect radiation induced mortality [8], it was observed that the AOX dietary supplement increased the 30-day survival of ICR male mice following exposure to a potentially lethal dose (8 Gy) of X-rays when given prior to or after animal irradiation. Pretreatment of animals with antioxidants resulted in significantly higher total white blood cell and neutrophil counts in peripheral blood at 4 and 24 hours following exposure to doses of 1 Gy and 8 Gy. Antioxidant treatment also resulted in increased bone marrow cell counts following irradiation, and prevented peripheral lymphopenia following 1 Gy irradiation. Supplementation with antioxidants in irradiated animals resulted in several gene expression changes: the antioxidant treatment was associated with increased Bcl-2, and decreased Bax, caspase-9 and TGF-β1 mRNA expression in the bone marrow following irradiation. These results suggest that modulation of apoptosis may be mechanistically involved in hematopoietic system radioprotection by antioxidants. Maintenance of the antioxidant diet was associated with improved recovery of the bone marrow following sub-lethal or potentially lethal irradiation. Taken together

  2. Mometasone Furoate Cream Reduces Acute Radiation Dermatitis in Patients Receiving Breast Radiation Therapy: Results of a Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hindley, Andrew, E-mail: andrew.hindley@lthtr.nhs.uk [Rosemere Cancer Centre, Royal Preston Hospital, Preston (United Kingdom); Zain, Zakiyah [College of Arts and Sciences, Universiti Utara Malaysia, Kedah (Malaysia); Wood, Lisa [Department of Social Sciences, Lancaster Medical School, Lancaster (United Kingdom); Whitehead, Anne [Medical and Pharmaceutical Statistics Research Unit, Lancaster University, Lancaster (United Kingdom); Sanneh, Alison; Barber, David; Hornsby, Ruth [Rosemere Cancer Centre, Royal Preston Hospital, Preston (United Kingdom)

    2014-11-15

    Purpose: We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Boström et al, Radiother Oncol 2001;59:257-265). Methods and Materials: The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Results: Mean RTOG scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean erythema scores were significantly less for MF than for D (P=.018 and P=.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. Conclusions: MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected.

  3. Granulocyte Colony-Stimulating Factor in the Treatment of Acute Radiation Syndrome: A Concise Review

    Directory of Open Access Journals (Sweden)

    Michal Hofer

    2014-04-01

    Full Text Available This article concisely summarizes data on the action of one of the principal and best known growth factors, the granulocyte colony-stimulating factor (G-CSF, in a mammalian organism exposed to radiation doses inducing acute radiation syndrome. Highlighted are the topics of its real or anticipated use in radiation accident victims, the timing of its administration, the possibilities of combining G-CSF with other drugs, the ability of other agents to stimulate endogenous G-CSF production, as well as of the capability of this growth factor to ameliorate not only the bone marrow radiation syndrome but also the gastrointestinal radiation syndrome. G-CSF is one of the pivotal drugs in the treatment of radiation accident victims and its employment in this indication can be expected to remain or even grow in the future.

  4. Interleukin-17A and Neutrophils in a Murine Model of Bird-Related Hypersensitivity Pneumonitis.

    Directory of Open Access Journals (Sweden)

    Masahiro Ishizuka

    Full Text Available Hypersensitivity pneumonitis (HP is an immune mediated lung disease induced by the repeated inhalation of a wide variety of antigens. Bird-related hypersensitivity pneumonitis (BRHP is one of the most common forms of HP in human and results from the inhalation of avian antigens. The findings of a recent clinical analysis suggest that in addition to Th1 factors, the levels of interleukin(IL-17 and IL-17-associated transcripts are increased in the setting of HP, and that both IL-17A and neutrophils are crucial for the development of pulmonary inflammation in murine models of HP. Our objectives were to investigate the roles of IL-17A and neutrophils in granuloma-forming inflammation in an acute HP model. We developed a mouse model of acute BRHP using pigeon dropping extract. We evaluated the process of granuloma formation and the roles of both IL-17A and neutrophils in a model. We found that the neutralization of IL-17A by the antibody attenuated granuloma formation and the recruitment of neutrophils, and also decreased the expression level of chemokine(C-X-C motif ligand 5 (CXCL5 in the acute HP model. We confirmed that most of the neutrophils in the acute HP model exhibited immunoreactivity to the anti-IL-17 antibody. We have identified the central roles of both IL-17A and neutrophils in the pathogenesis of granuloma formation in acute HP. We have also assumed that neutrophils are an important source of IL-17A in an acute HP model, and that the IL-17A-CXCL5 pathway may be responsible for the recruitment of neutrophils.

  5. Supplemental vitamin A prevents the acute radiation-induced defect in wound healing

    Energy Technology Data Exchange (ETDEWEB)

    Levenson, S.M.; Gruber, C.A.; Rettura, G.; Gruber, D.K.; Demetriou, A.A.; Seifter, E.

    1984-10-01

    Acute radiation injury leads to thymic involution, adrenal enlargement, leukopenia, thrombocytopenia, gastrointestinal ulceration, and impaired wound healing. The authors hypothesized that supplemental vitamin A would mitigate these adverse effects in rats exposed to acute whole-body radiation. To test their hypothesis, dorsal skin incisions and subcutaneous implantation of polyvinyl alcohol sponges were performed in anesthetized Sprague-Dawley rats at varying times following sham radiation or varying doses of whole-body radiation (175-850 rad). In each experiment, the control diet (which contains about 18,000 IU vit. A/kg chow (3 X the NRC RDA for normal rats)) was supplemented with 150,000 IU vit. A/kg diet beginning at, before, or after sham radiation and wounding or radiation and wounding. The supplemental vitamin A prevented the impaired wound healing and lessened the weight loss, leukopenia, thrombocytopenia, thymic involution, adrenal enlargement, decrease in splenic weight, and gastric ulceration of the radiated (750-850 rad) wounded rats. This was true whether the supplemental vitamin A was begun before (2 or 4 days) or after (1-2 hours to 4 days) radiation and wounding; the supplemental vitamin A was more effective when started before or up to 2 days after radiation and wounding. The authors believe that prevention of the impaired wound healing following radiation by supplemental vitamin A is due to its enhancing the early inflammatory reaction to wounding, including increasing the number of monocytes and macrophages at the wound site; possible effect on modulating collagenase activity; effect on epithelial cell (and possible mesenchymal cell) differentiation; stimulation of immune responsiveness; and lessening of the adverse effects of radiation.

  6. The effect of tetrandrine and extracts of centella asiatica on acute radiation dermatitis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu-Jen; Dai, Yu-Shiang; Chen, Be-Fong [Mackay Memorial Hospital, TW (China)] [and others

    1999-07-01

    Radiation injury to the skin is one of the major limiting factors in radiotherapy. We designed this study using Sprague-Dawley rats to evaluate the reduction in skin injury achieved using natural products from plant extracts as protection. The acute skin reaction in tetrandrine- and Madecassol-treated animals appeared earlier, but was significantly less severe, than in the control group. The peak skin reactions in the tetrandrine group were less serious than those of the control group at three different radiation doses. At a high dose irradiation, the healing effect of tetrandrine is better than Madecassol and vaseline. The histologic findings indicate that tetrandrine and Madecassol are able to reduce acute radiation reactions by their anti-inflammatory activity. (author)

  7. Chanqes of osseous tissue following radiation therapy and in acute radiation trauma

    Energy Technology Data Exchange (ETDEWEB)

    Krylov, V.M.

    1982-11-01

    The studies on ionizing radiation effect with harmful doses on man skeleton are analyzed. Pathomorphological and roentgenological changes in bones of patients, who underwent radiotherapy course are studied; the pointed out changes were observed as radiation complications. It is noted that pathological process in the bone develops comparatively slowly following therapeutic fractionated irradiation.

  8. Plague in China 2014-All sporadic case report of pneumonic plague.

    Science.gov (United States)

    Li, Yun-Fang; Li, De-Biao; Shao, Hong-Sheng; Li, Hong-Jun; Han, Yue-Dong

    2016-02-19

    Yersinia pestis is the pathogen of the plague and caused three pandemics worldwide. Pneumonic plague is rarer than bubonic and septicemic plague. We report detailed clinical and pathogenic data for all the three sporadic cases of pneumonic plagues in China in 2014. All the three patients are herders in Gansu province of China. They were all infected by Yersinia pestis and displayed in the form of pneumonic plague respectively without related. We tested patient specimens from the upper (nasopharyngeal swabs) or the lower (sputum) respiratory tract and whole blood, plasma, and serum specimens for Yersinia pestis. All patients had fever, cough and dyspnea, and for patient 2 and 3, unconscious. Respiratory symptoms were predominant with acute respiratory failure. The chest X-ray showed signs consistent with necrotizing inflammation with multiple lobar involvements. Despite emergency treatment, all patients died of refractory multiple organ failure within 24 h after admission to hospital. All the contacts were quarantined immediately and there were no secondary cases. Nowadays, the plague is epidemic in animals and can infect people who contact with the infected animals which may cause an epidemic in human. We think dogs maybe an intermediate vector for plague and as a source of risk for humans who are exposed to pet animals or who work professionally with canines. If a patient has been exposed to a risk factor and has fever and dyspnea, plague should be considered. People who had contact with a confirmed case should be isolated and investigated for F1 antigen analysis and receive post-exposure preventive treatment. A vaccination strategy might be useful for individuals who are occupationally exposed in areas where endemically infected reservoirs of plague-infected small mammals co-exist.

  9. Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J.I.

    1982-08-01

    The present review provides an understanding of our current knowledge of the carcinogenic effect of low-dose radiation in man, and surveys the epidemiological studies of human populations exposed to nuclear explosions and medical radiation. Discussion centers on the contributions of quantitative epidemiology to present knowledge, the reliability of the dose-incidence data, and those relevant epidemiological studies that provide the most useful information for risk estimation of cancer-induction in man. Reference is made to dose-incidence relationships from laboratory animal experiments where they may obtain for problems and difficulties in extrapolation from data obtained at high doses to low doses, and from animal data to the human situation. The paper describes the methods of application of such epidemiological data for estimation of excess risk of radiation-induced cancer in exposed human populations, and discusses the strengths and limitations of epidemiology in guiding radiation protection philosophy and public health policy.

  10. Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J.I.

    1982-08-01

    The present review provides an understanding of our current knowledge of the carcinogenic effect of low-dose radiation in man, and surveys the epidemiological studies of human populations exposed to nuclear explosions and medical radiation. Discussion centers on the contributions of quantitative epidemiology to present knowledge, the reliability of the dose-incidence data, and those relevant epidemiological studies that provide the most useful information for risk estimation of cancer-induction in man. Reference is made to dose-incidence relationships from laboratory animal experiments where they may obtain for problems and difficulties in extrapolation from data obtained at high doses to low doses, and from animal data to the human situation. The paper describes the methods of application of such epidemiological data for estimation of excess risk of radiation-induced cancer in exposed human populations, and discusses the strengths and limitations of epidemiology in guiding radiation protection philosophy and public health policy.

  11. Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J.I.

    1981-05-01

    The current knowledge of the carcinogenic effect of radiation in man is considered. The discussion is restricted to dose-incidence data in humans, particularly to certain of those epidemiological studies of human populations that are used most frequently for risk estimation for low-dose radiation carcinogenesis in man. Emphasis is placed solely on those surveys concerned with nuclear explosions and medical exposures. (ACR)

  12. Which place for stem cell therapy in the treatment of acute radiation syndrome?

    Directory of Open Access Journals (Sweden)

    Jean-François Mayol

    2005-12-01

    Full Text Available Radiation-induced (RI tissue injuries can be caused by radiation therapy, nuclear accidents or radiological terrorism. Notwithstanding the complexity of RI pathophysiology, there are some effective approaches to treatment of both acute and chronic radiation damages. Cytokine therapy is the main strategy capable of preventing or reducing the acute radiation syndrome (ARS, and hematopoietic growth factors (GF are particularly effective in mitigating bone marrow (BM aplasia and stimulating hematopoietic recovery. However, first, as a consequence of RI stem and progenitor cell death, use of cytokines should be restricted to a range of intermediate radiation doses (3 to 7 Gy total body irradiation. Second, ARS is a global illness that requires treatment of damages to other tissues (epithelial, endothelial, glial, etc., which could be achieved using pleiotropic or tissue-specific cytokines. Stem cell therapy (SCT is a promising approach developed in the laboratory that could expand the ability to treat severe radiation injuries. Allogeneic hematopoietic stem cell transplantation (BM, mobilized peripheral blood and cord blood transplantation has been used in radiation casualties with variable success due to limiting toxicity related to the degree of graft histocompatibility and combined injuries. Ex vivo expansion should be used to augment cord blood graft size and/or promote very immature stem cells. Autologous SCT might also be applied to radiation casualties from residual hematopoietic stem and progenitor cells (HSPC. Stem cell plasticity of different tissues such as liver or skeletal muscle, may also be used as a source of hematopoietic stem cells. Finally, other types of stem cells such as mesenchymal, endothelial stem cells or other tissue committed stem cells (TCSC, could be used for treating damages to nonhematopoietic organs.

  13. Immuno-therapy of Acute Radiation Syndromes : Extracorporeal Immuno-Lympho-Plasmo-Sorption.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava

    Methods Results Summary and conclusions Introduction: Existing Medical Management of the Acute Radiation Syndromes (ARS) does not include methods of specific immunotherapy and active detoxication. Though the Acute Radiation Syndromes were defined as an acute toxic poisonous with development of pathological processes: Systemic Inflammatory Response Syndrome (SIRS), Toxic Multiple Organ Injury (TMOI), Toxic Multiple Organ Dysfunction Syndrome(TMODS), Toxic Multiple Organ Failure (TMOF). Radiation Toxins of SRD Group play an important role as the trigger mechanisms in development of the ARS clinical symptoms. Methods: Immuno-Lympho-Plasmo-Sorption is a type of Immuno-therapy which includes prin-ciples of immunochromato-graphy, plasmopheresis, and hemodialysis. Specific Antiradiation Antitoxic Antibodies are the active pharmacological agents of immunotherapy . Antiradia-tion Antitoxic Antibodies bind selectively to Radiation Neurotoxins, Cytotoxins, Hematotox-ins and neutralize their toxic activity. We have developed the highly sensitive method and system for extracorporeal-immune-lypmh-plasmo-sorption with antigen-specific IgG which is clinically important for treatment of the toxic and immunologic phases of the ARS. The method of extracorporeal-immune-lypmh-plasmo-sorption includes Antiradiation Antitoxic Antibodies (AAA) immobilized on microporous polymeric membranes with a pore size that is capable to provide diffusion of blood-lymph plasma. Plasma of blood or lymph of irradiated mammals contains Radiation Toxins (RT) that have toxic and antigenic properties. Radiation Toxins are Antigen-specific to Antitoxic blocking antibodies (Immunoglobulin G). Plasma diffuses through membranes with immobilized AAA and AA-antibodies bind to the polysaccharide chain of tox-ins molecules and complexes of AAA-RT that are captured on membrane surfaces. RT were removed from plasma. Re-transfusion of plasma of blood and lymph had been provided. We show a statistical significant

  14. Acute biological effects of simulating the whole-body radiation dose distribution from a solar particle event using a porcine model.

    Science.gov (United States)

    Wilson, Jolaine M; Sanzari, Jenine K; Diffenderfer, Eric S; Yee, Stephanie S; Seykora, John T; Maks, Casey; Ware, Jeffrey H; Litt, Harold I; Reetz, Jennifer A; McDonough, James; Weissman, Drew; Kennedy, Ann R; Cengel, Keith A

    2011-11-01

    In a solar particle event (SPE), an unshielded astronaut would receive proton radiation with an energy profile that produces a highly inhomogeneous dose distribution (skin receiving a greater dose than internal organs). The novel concept of using megavoltage electron-beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation has been described previously. Here, Yucatan minipigs were used to determine the effects of a superficial, SPE-like proton dose distribution using megavoltage electrons. In these experiments, dose-dependent increases in skin pigmentation, ulceration, keratinocyte necrosis and pigment incontinence were observed. Five of 18 animals (one each exposed to 7.5 Gy and 12.5 Gy radiation and three exposed to 25 Gy radiation) developed symptomatic, radiation-associated pneumonopathy approximately 90 days postirradiation. The three animals from the highest dose group showed evidence of mycoplasmal pneumonia along with radiation pneumonitis. Moreover, delayed-type hypersensitivity was found to be altered, suggesting that superficial irradiation of the skin with ionizing radiation might cause immune dysfunction or dysregulation. In conclusion, using total doses, patterns of dose distribution, and dose rates that are compatible with potential astronaut exposure to SPE radiation, animals experienced significant toxicities that were qualitatively different from toxicities previously reported in pigs for homogeneously delivered radiation at similar doses.

  15. Topical Calendula and Betamethasone Valerate in the prevention of acute radiation dermatitis: a randomized prospective trial

    Directory of Open Access Journals (Sweden)

    Fotouhi M

    2007-07-01

    Full Text Available Background: Acute radiation dermatitis is a very common side effect of radiation therapy for many cancers, including breast cancer. Despite the high prevalence of acute radiation dermatitis as well as wet desquamation, only a few trials studying the prophylaxis of this complication using topical treatment have been conducted. In spite of these studies, some controversy still exists about regarding treatments for acute radiation dermatitis, as does some concern about their long-term complications. For this reason, we conducted a clinical trial for a new treatment with the same effectiveness as corticosteroids, but fewer complications. Methods: This trial included 60 patients with pathologic diagnoses of breast cancer for whom radiotherapy had been planned. Patients were 30-73 years old. Patients with radical mastectomy received 5000 cGy over five weeks, and those with conservative surgery received 6000 cGy over six weeks divided in 200 cGy fractions. Patients were divided randomly into two groups: one group received a moderately-potent glucocorticoid steroid, 0.1% betamethasone ointment (30, and the other received the new treatment, 0.1% calendula ointment (30. All patients applied their respective drugs twice daily within the tangential field from the first day of radiation treatment until one month after treatment was completed. Starting one week after radiation therapy commenced, patients were monitored weekly for symptoms of dermatitis and the degree of severity as well as possible adverse drug effects, in addition to such monitoring on the days of their appointments. Four weeks after termination of therapy, patients were again examined, at which time they completed a questionnaire about dermatologic complications. Results: The mean time to develop dermatitis was 3.7 weeks for the betamethasone group and 3.87 weeks for the calendula group. Maximal dermatitis intensity during treatment in the betamethasone group was: 0, 6.7%; I, 73.3%; II, 16

  16. European consensus on the medical management of acute radiation syndrome and analysis of the radiation accidents in Belgium and Senegal.

    Science.gov (United States)

    Gourmelon, Patrick; Benderitter, Marc; Bertho, Jean Marc; Huet, Christelle; Gorin, Norbert Claude; De Revel, Patrick

    2010-06-01

    A European consensus concerning the medical management of mass radiation exposure was obtained in 2005 during a conference held by the European Group for Blood and Bone Marrow Transplantation, the Institute of Radioprotection and Nuclear Safety, and the University of Ulm. At the conference, a two-step triage strategy to deal with large masses of radiation-exposed patients was designed. The first step of this strategy concerns the first 48 h and involves scoring the patients exclusively on the basis of their clinical symptoms and biological data. This allows the non-irradiated bystanders and outpatient candidates to be identified. The remaining patients are hospitalized and diagnosis is confirmed after the first 48-h period according to the METREPOL (Medical Treatment Protocols for radiation accident victims) scale. This grades the patients according to the severity of their symptoms. It was also agreed that in the case of acute radiation syndrome (ARS), emergency hematopoietic stem cell (HSC) transplantation is not necessary. Instead, cytokines that promote hematological reconstruction should be administered as early as possible for 14-21 d. Crucial tests for determining whether the patient has residual hematopoiesis are physical dose reconstructions combined with daily blood count analyses. It was agreed that HSC transplantation should only be considered if severe aplasia persists after cytokine treatment. Two recent cases of accidental radiation exposure that were managed successfully by following the European consensus with modification are reviewed here. Thus, a European standard for the evaluation and treatment of ARS victims is now available. This standard may be suitable for application around the world.

  17. Evidence Report: Risk of Acute Radiation Syndromes Due to Solar Particle Events

    Science.gov (United States)

    Carnell, Lisa; Blattnig, Steve; Hu, Shaowen; Huff, Janice; Kim, Myung-Hee; Norman, Ryan; Patel, Zarana; Simonsen, Lisa; Wu, Honglu

    2016-01-01

    Crew health and performance may be impacted by a major solar particle event (SPE), multiple SPEs, or the cumulative effect of galactic cosmic rays (GCR) and SPEs. Beyond low-Earth orbit, the protection of the Earth's magnetosphere is no longer available, such that increased shielding and protective mechanisms are necessary in order to prevent acute radiation sickness and impacts to mission success or crew survival. While operational monitoring and shielding are expected to minimize radiation exposures, there are EVA scenarios outside of low-Earth orbit where the risk of prodromal effects, including nausea, vomiting, anorexia, and fatigue, as well as skin injury and depletion of the blood-forming organs (BFO), may occur. There is a reasonable concern that a compromised immune system due to high skin doses from a SPE or due to synergistic space flight factors (e.g., microgravity) may lead to increased risk to the BFO. The primary data available at present are derived from analyses of medical patients and persons accidentally exposed to acute, high doses of low-linear energy transfer (LET) (or terrestrial) radiation. Data more specific to the space flight environment must be compiled to quantify the magnitude of increase of this risk and to develop appropriate protection strategies. In particular, information addressing the distinct differences between solar proton exposures and terrestrial exposure scenarios, including radiation quality, dose-rate effects, and non-uniform dose distributions, is required for accurate risk estimation.

  18. Pathogenesis of acute radiation effects in the urinary bladder. Experimental results

    Energy Technology Data Exchange (ETDEWEB)

    Doerr, W.; Eckhardt, M.; Ehme, A.; Koi, S. [Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Technische Univ. Dresden (Germany)

    1998-11-01

    Purpose: The present review summarizes experimental studies of the pathogenesis of acute radiation-induced changes in urinary bladder function. Material and methods: Transurethral cystometry was used for longitudinal assessment of bladder function in mice. With this technique, radition-induced changes in storage capacity can be quantified. In histological studies, changes in urothelial cell density and in urothelial protein expression during the acute radiation response were determined. Acetylsalicylic acid (ASA) was used for the treatment of acute functional changes. Results: The histological studies did not reveal any systematic fluctuations in urothelial cell density during the time of the acute radiation response. However, characteristic changes in the expression of proteins associated with urothelial cell function, differentiation and cell contact were observed, which correlated with the functional impairment. By local or systemical application of ASA, a significant restoration of bladder function compared to placebo treatment could be achieved. Conclusion: Acute functional radiation effects in the urinary bladder are not based on urothelial denudation. However, changes in protein expression indicate an impairment of the urothelial barrier function. The results of ASA treatment demonstrate that prostaglandins are involved in the response. Alterations in urothelial or endothelial prostaglandin metabolism may be primarily radiation-induced or secondary because of the impaired urothelial barrier. (orig.) [Deutsch] Ziel: Die vorliegende Arbeit soll tierexperimentelle Ergebnisse zur Pathogenese akuter Funktionsstoerungen der Harnblase nach Bestrahlung zusammenfassen. Material und Methoden: Transurethrale zystometrische Messungen dienen zur longitudinalen Erfassung der Harnblasenfunktion bei der Maus. Mit dieser Methode koennen strahlenbedingte Stoerungen der Speicherkapazitaet quantifiziert werden. In histologischen Untersuchungen wurden Veraenderungen in der

  19. Acute Hematological Effects of Solar Particle Event Proton Radiation in the Porcine Model

    Science.gov (United States)

    Sanzari, J. K.; Wan, X. S.; Wroe, A. J.; Rightnar, S.; Cengel, K. A.; Diffenderfer, E. S.; Krigsfeld, G. S.; Gridley, D. S.; Kennedy, A. R.

    2013-01-01

    Acute radiation sickness (ARS) is expected to occur in astronauts during large solar particle events (SPEs). One parameter associated with ARS is the hematopoietic syndrome, which can result from decreased numbers of circulating blood cells in those exposed to radiation. The peripheral blood cells are critical for an adequate immune response, and low blood cell counts can result in an increased susceptibility to infection. In this study, Yucatan minipigs were exposed to proton radiation within a range of skin dose levels expected for an SPE (estimated from previous SPEs). The proton-radiation exposure resulted in significant decreases in total white blood cell count (WBC) within 1 day of exposure, 60% below baseline control value or preirradiation values. At the lowest level of the blood cell counts, lymphocytes, neutrophils, monocytes and eosinophils were decreased up to 89.5%, 60.4%, 73.2% and 75.5%, respectively, from the preirradiation values. Monocytes and lymphocytes were decreased by an average of 70% (compared to preirradiation values) as early as 4 h after radiation exposure. Skin doses greater than 5 Gy resulted in decreased blood cell counts up to 90 days after exposure. The results reported here are similar to studies of ARS using the nonhuman primate model, supporting the use of the Yucatan minipig as an alternative. In addition, the high prevalence of hematologic abnormalities resulting from exposure to acute, whole-body SPE-like proton radiation warrants the development of appropriate countermeasures to prevent or treat ARS occurring in astronauts during space travel. PMID:23672458

  20. Clinical presentation of acute Q fever in Spain: seasonal and geographical differences

    Directory of Open Access Journals (Sweden)

    Elena Espejo

    2014-09-01

    Conclusions: Our results suggest the existence of seasonal differences in the presentation of acute Q fever in Spain, with a higher proportion of pneumonic forms in the colder months. Furthermore, we confirmed the existence of geographical differences, with a higher proportion of pneumonic forms in the region of La Rioja, in the north of the country.

  1. Acute and subacute chemical-induced lung injuries: HRCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Akira, Masanori, E-mail: Akira@kch.hosp.go.jp [Department of Radiology, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai City, Osaka 591-8555 (Japan); Suganuma, Narufumi [Department of Environmental Medicine, Kochi Medical School (Japan)

    2014-08-15

    Lung injury caused by chemicals includes bronchitis, bronchiolitis, chemical pneumonitis, pulmonary edema, acute respiratory distress syndrome, organizing pneumonia, hypersensitivity pneumonitis, acute eosinophilic pneumonia, and sarcoid-like granulomatous lung disease. Each chemical induces variable pathophysiology and the situation resembles to the drug induced lung disease. The HRCT features are variable and nonspecific, however HRCT may be useful in the evaluation of the lung injuries and so we should know about HRCT features of lung parenchymal abnormalities caused by chemicals.

  2. Acute radiation hypotension in the rabbit: a model for the human radiation shock syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Makale, M.T.

    1987-01-01

    This study has shown that total body irradiation (TBI) of immature rabbits leads to an acute fall in mean arterial pressures (MAP) 30 to 90 minutes after exposure, which takes no more than about three minutes, and often results in pressures which are less than 50% of the lowest pre-exposure MAP. This is termed acute cardiovascular collapse (ACC). ACC is often accompanied by ECG T-wave elevation, a sharp rise in ear temperatures, labored breathing, pupillary constriction, bladder emptying, and loss of abdominal muscle tone. About 73% of 40 to 100 day rabbits exhibit ACC; the others and most older rabbits display gradual pressure reductions (deliberate hypotension) which may be profound, and which may be accompanied by the same changes associated with ACC. ACC and deliberate hypotension occurred in rabbits cannulated in the dorsal aorta, and in non-operated animals. The decline in MAP for all 40 to 100 day cannulated rabbits (deliberate and ACC responders) is 55.4%.

  3. The utility of acoustic radiation force impulse imaging in diagnosing acute appendicitis and staging its severity

    Science.gov (United States)

    Göya, Cemil; Hamidi, Cihad; Okur, Mehmet Hanifi; İçer, Mustafa; Oğuz, Abdullah; Hattapoğlu, Salih; Çetinçakmak, Mehmet Güli; Teke, Memik

    2014-01-01

    PURPOSE The aim of this study was to investigate the feasibility of using acoustic radiation force impulse (ARFI) imaging to diagnose acute appendicitis. METHODS Abdominal ultrasonography (US) and ARFI imaging were performed in 53 patients that presented with right lower quadrant pain, and the results were compared with those obtained in 52 healthy subjects. Qualitative evaluation of the patients was conducted by Virtual Touch™ tissue imaging (VTI), while quantitative evaluation was performed by Virtual Touch™ tissue quantification (VTQ) measuring the shear wave velocity (SWV). The severity of appendix inflammation was observed and rated using ARFI imaging in patients diagnosed with acute appendicitis. Alvarado scores were determined for all patients presenting with right lower quadrant pain. All patients diagnosed with appendicitis received appendectomies. The sensitivity and specificity of ARFI imaging relative to US was determined upon confirming the diagnosis of acute appendicitis via histopathological analysis. RESULTS The Alvarado score had a sensitivity and specificity of 70.8% and 20%, respectively, in detecting acute appendicitis. Abdominal US had 83.3% sensitivity and 80% specificity, while ARFI imaging had 100% sensitivity and 98% specificity, in diagnosing acute appendicitis. The median SWV value was 1.11 m/s (range, 0.6–1.56 m/s) for healthy appendix and 3.07 m/s (range, 1.37–4.78 m/s) for acute appendicitis. CONCLUSION ARFI imaging may be useful in guiding the clinical management of acute appendicitis, by helping its diagnosis and determining the severity of appendix inflammation. PMID:25323836

  4. Frequency, treatment, and functional outcome in children with hypersensitivity pneumonitis

    DEFF Research Database (Denmark)

    Buchvald, Frederik; Petersen, Bodil Laub; Damgaard, Karen;

    2011-01-01

    Hypersensitivity pneumonitis is a rare interstitial lung disease and very few data regarding frequency, treatment and outcome exist for children. Children identified with hypersensitivity pneumonia from a Danish national cohort with diffuse interstitial lung disease form the basis of this study...... focused on disease frequency, treatment, and functional outcome....

  5. [Persistent tachypnea in infants: possibly due to interstitial pneumonitis

    NARCIS (Netherlands)

    Kingma, M.L.; Nef, J.J.E.M. de; Krieken, J.H.J.M. van; Merth, I.T.

    2002-01-01

    In three male infants aged 3, 4.5 and 11 months with tachypnea and feeding problems, the initial supplementary examination revealed no possible cause. The tissue obtained by open lung biopsy showed interstitial pneumonia/pneumonitis. The two youngest patients were treated with hydrochloroquine and p

  6. The pathogenesis of Chlamydia pneumoniae-type pneumonitis in mice

    Institute of Scientific and Technical Information of China (English)

    施毅; 印洁; 詹化文; 冯根宝; 张希龙; 苏欣; 宋勇; 夏锡荣; 周晓军; 申萍

    2003-01-01

    Objective To evaluate mice as experimental animals for Chlamydia pneumoniae (C.pneumoniae) infection and investigate the pathogenesis of C.pneumoniae derived pneumonitis.Methods Icr mice were inoculated with the C.pneumoniae strain, CWL-029, either intranasally or intravenously. After a single dose inoculation, mice were killed on the 1st, 3rd, 7th, 14th, 21st, 28th and 60th days. The pathological changes in lung tissue were analyzed.Results The Icr mice were shown to be susceptible to C.pneumoniae. Inoculation into mice with C.pneumoniae induced a prolonged course of lung infection, as demonstrated by persistence of lung pathology (up to 60 days). Via intranasal inoculation of mice, lung pathology was characterized by patchy interstitial pneumonitis with predominately neutrophil leukocyte infiltration early (within the first 7 days) and lymphocyte infiltration in the later stages (14 days later) of infection. After intravenous inoculation, a similarly developed interstitial pneumonitis was observed, but it was milder and patchier, especially in early stages. C.pneumoniae DNA was detected by polymerase chain reaction (PCR) intermittently in the lung tissue. Inoculated mice developed serum IgG antibody responses.Conclusion The Icr mice were susceptible to C.pneumoniae, resulting in a pulmonary infection characterized by interstitial pneumonitis, occurring most strongly via intranasal inoculation.

  7. Interstitial pneumonitis after acetylene welding: a case report.

    Science.gov (United States)

    Brvar, Miran

    2014-01-01

    Acetylene is a colorless gas commonly used for welding. It acts mainly as a simple asphyxiant. In this paper, however, we present a patient who developed a severe interstitial pneumonitis after acetylene exposure during aluminum welding. A 44-year old man was welding with acetylene, argon and aluminum electrode sticks in a non-ventilated aluminum tank for 2 h. Four hours after welding dyspnea appeared and 22 h later he was admitted at the Emergency Department due to severe respiratory insufficiency with pO2 = 6.7 kPa. Chest X-ray showed diffuse interstitial infiltration. Pulmonary function and gas diffusion tests revealed a severe restriction (55% of predictive volume) and impaired diffusion capacity (47% of predicted capacity). Toxic interstitial pneumonitis was diagnosed and high-dose systemic corticosteroid methylprednisolone and inhalatory corticosteroid fluticasone therapy was started. Computed Tomography (CT) of the lungs showed a diffuse patchy ground-glass opacity with no signs of small airway disease associated with interstitial pneumonitis. Corticosteroid therapy was continued for the next 8 weeks gradually reducing the doses. The patient's follow-up did not show any deterioration of respiratory function. In conclusion, acetylene welding might result in severe toxic interstitial pneumonitis that improves after an early systemic and inhalatory corticosteroid therapy.

  8. Overview of Graphical User Interface for ARRBOD (Acute Radiation Risk and BRYNTRN Organ Dose Projection)

    Science.gov (United States)

    Kim, Myung-Hee Y.; Hu, Shaowen; Nounu, Hatem; Cucinotta, Francis A.

    Solar particle events (SPEs) pose the risk of acute radiation sickness (ARS) to astronauts be-cause organ doses from large SPEs may reach critical levels during extra vehicular activities (EVAs) or lightly shielded spacecraft. NASA has developed an organ dose projection model of Baryon transport code (BRYNTRN) with an output data processing module of SUMDOSE, and a probabilistic model of acute radiation risk (ARR). BRYNTRN code operation requires extensive input preparation, and the risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, these response models can be connected easily and correctly to BRYNTRN in a user-friendly way. The GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations direc-torate (MOD), and space biophysics researchers. Assessment of astronauts' organ doses and ARS from the exposure to historically large SPEs is in support of mission design and opera-tion planning to avoid ARS and stay within the current NASA short-term dose limits. The ARRBOD GUI will serve as a proof-of-concept for future integration of other risk projection models for human space applications. We present an overview of the ARRBOD GUI prod-uct, which is a new self-contained product, for the major components of the overall system, subsystem interconnections, and external interfaces.

  9. Association of Acute Radiation Syndrome and Rain after the Bombings in Atomic Bomb Survivors.

    Science.gov (United States)

    Ozasa, K; Sakata, R; Cullings, H M; Grant, E J

    2016-06-01

    Acute radiation-induced symptoms reported in survivors after the atomic bombings in Hiroshima and Nagasaki have been suspected to be associated with rain that fell after the explosions, but this association has not been evaluated in an epidemiological study that considers the effects of the direct dose from the atomic bombs and other factors. The aim of this study was to evaluate this association using information from a fixed cohort, comprised of 93,741 members of the Life Span Study who were in the city at the time of the bombing. Information on acute symptoms and exposure to rain was collected in surveys conducted by interviewers, primarily in the 1950s. The proportion of survivors developing severe epilation was around 60% at levels of direct radiation doses of 3 Gy or higher and less than 0.2% at levels <0.005 Gy regardless of reported rain exposure status. The low prevalence of acute symptoms at low direct doses indicates that the reported fallout rain was not homogeneously radioactive at a level sufficient to cause a substantial probability of acute symptoms. We observed that the proportion of reported acute symptoms was slightly higher among those who reported rain exposure in some subgroups, however, suggestions that rain was the cause of these reported symptoms are not supported by analyses specific to the known areas of radioactive fallout. Misclassification of exposure and outcome, including symptoms due to other causes and recall bias, appears to be a more plausible explanation. However, the insufficient and retrospective nature of the available data limited our ability to quantify the attribution to those possible causes.

  10. Inhaled /sup 147/Pm and/or total-body gamma radiation: Early mortality and morbidity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Filipy, R.E.; Lauhala, K.E.; McGee, D.R.; Cannon, W.C.; Buschbom, R.L.; Decker, J.R.; Kuffel, E.G.; Park, J.F.; Ragan, H.A.; Yaniv, S.S.; Scott, B.R.

    1989-05-01

    Rats were given doses of /sup 60/Co gamma radiation and/or lung burdens of /sup 147/Pm (in fused aluminosilicate particles) within lethal ranges in an experiment to determine and compare morbidity and mortality responses for the radiation insults within 1 year after exposure. Radiation-induced morbidity was assessed by measuring changes in body weights, hematologic parameters, and pulmonary-function parameters. Acute mortality and morbidity from inhaled promethium were caused primarily by radiation pneumonitis and pulmonary fibrosis that occurred more than 53 days after exposure. Acute mortality and morbidity from total-body gamma irradiation occurred within 30 days of exposure and resulted from the bone-marrow radiation syndrome. Gamma radiation caused transient morbidity, reflected by immediately depressed blood cell levels and by reduced body weight gain in animals that survived the acute gamma radiation syndrome. Inhaled promethium caused a loss of body weight and diminished pulmonary function, but its only effect on blood cell levels was lymphocytopenia. Combined gamma irradiation and promethium lung burdens were synergistic, in that animals receiving both radiation insults had higher morbidity and mortality rates than would be predicted based on the effect of either kind of radiation alone. Promethium lung burdens enhanced the effect of gamma radiation in rats within the first 30 days of exposure, and gamma radiation enhanced the later effect of promethium lung burdens. 70 refs., 68 figs., 21 tabs.

  11. Chemical toxicity of uranium hexafluoride compared to acute effects of radiation

    Energy Technology Data Exchange (ETDEWEB)

    McGuire, S.A.

    1991-02-01

    The chemical effects from acute exposures to uranium hexafluoride are compared to the nonstochastic effects from acute radiation doses of 25 rems to the whole body and 300 rems to the thyroid. The analysis concludes that an intake of about 10 mg of uranium in soluble form is roughly comparable, in terms of early effects, to an acute whole body dose of 25 rems because both are just below the threshold for significant nonstochastic effects. Similarly, an exposure to hydrogen fluoride at a concentration of 25 mg/m{sup 3} for 30 minutes is roughly comparable because there would be no significant nonstochastic effects. For times t other than 30 minutes, the concentration C of hydrogen fluoride considered to have the same effect can be calculated using a quadratic equation: C = 25 mg/m{sup 3} (30 min/t). The purpose of these analyses is to provide information for developing design and siting guideline based on chemical toxicity for enrichment plants using uranium hexafluoride. These guidelines are to be similar, in terms of stochastic health effects, to criteria in NRC regulations of nuclear power plants, which are based on radiation doses. 26 refs., 1 fig., 5 tabs.

  12. Dosimetric Predictors of Radiation-induced Acute Nausea and Vomiting in IMRT for Nasopharyngeal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Victor H.F., E-mail: vhflee@hku.hk [Department of Clinical Oncology, University of Hong Kong, Queen Mary Hospital (Hong Kong); Ng, Sherry C.Y.; Leung, T.W.; Au, Gordon K.H.; Kwong, Dora L.W. [Department of Clinical Oncology, University of Hong Kong, Queen Mary Hospital (Hong Kong)

    2012-09-01

    Purpose: We wanted to investigate dosimetric parameters that would predict radiation-induced acute nausea and vomiting in intensity-modulated radiation therapy (IMRT) for undifferentiated carcinoma of the nasopharynx (NPC). Methods and Materials: Forty-nine consecutive patients with newly diagnosed NPC were treated with IMRT alone in this prospective study. Patients receiving any form of chemotherapy were excluded. The dorsal vagal complex (DVC) as well as the left and right vestibules (VB-L and VB-R, respectively) were contoured on planning computed tomography images. A structure combining both the VB-L and the VB-R, named VB-T, was also generated. All structures were labeled organs at risk (OAR). A 3-mm three-dimensional margin was added to these structures and labeled DVC+3 mm, VB-L+3 mm, VB-R+3 mm, and VB-T+3 mm to account for physiological body motion and setup error. No weightings were given to these structures during optimization in treatment planning. Dosimetric parameters were recorded from dose-volume histograms. Statistical analysis of parameters' association with nausea and vomiting was performed using univariate and multivariate logistic regression. Results: Six patients (12.2%) reported Grade 1 nausea, and 8 patients (16.3%) reported Grade 2 nausea. Also, 4 patients (8.2%) complained of Grade 1 vomiting, and 4 patients (8.2%) experienced Grade 2 vomiting. No patients developed protracted nausea and vomiting after completion of IMRT. For radiation-induced acute nausea, V40 (percentage volume receiving at least 40Gy) to the VB-T and V40>=80% to the VB-T were predictors, using univariate analysis. On multivariate analysis, V40>=80% to the VB-T was the only predictor. There were no predictors of radiation-induced acute vomiting, as the number of events was too small for analysis. Conclusions: This is the first study demonstrating that a V40 to the VB-T is predictive of radiation-induced acute nausea. The vestibules should be labeled as sensitive OARs

  13. Hypersensitivity pneumonitis and exposure to zirconium silicate in a young ceramic tile worker.

    Science.gov (United States)

    Liippo, K K; Anttila, S L; Taikina-Aho, O; Ruokonen, E L; Toivonen, S T; Tuomi, T

    1993-10-01

    We describe a nonsmoking ceramic tile worker 25 yr of age who developed a worsening dry cough and dyspnea after 3.5 yr as a sorter and glazer of tiles. Open lung biopsy revealed an intense granulomatous interstitial pneumonia with mild fibrosis, compatible with hypersensitivity pneumonitis, and numerous very small birefringent crystals around the terminal airways and occasionally in granulomas. Pulmonary particle analysis revealed an inhaled dust burden nearly 100-fold the normal background level, mainly consisting of clay minerals and zirconium silicate. The patient had no history or clinical or laboratory findings suggesting any organic etiologic agent. A sarcoid granulomatosis type of chronic pulmonary hypersensitivity reaction is known after long-term exposure to zirconium, but this case demonstrates that zirconium can also cause an acute and fulminant allergic alveolitislike hypersensitivity reaction.

  14. Ecological effects of various toxic agents on the aquatic microcosm in comparison with acute ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fuma, S. E-mail: fuma@nirs.go.jp; Ishii, N.; Takeda, H.; Miyamoto, K.; Yanagisawa, K.; Ichimasa, Y.; Saito, M.; Kawabata, Z.; Polikarpov, G.G

    2003-07-01

    The purpose of this study was an evaluation of the effect levels of various toxic agents compared with acute doses of ionizing radiation for the experimental model ecosystem, i.e., microcosm mimicking aquatic microbial communities. For this purpose, the authors used the microcosm consisting of populations of the flagellate alga Euglena gracilis as a producer, the ciliate protozoan Tetrahymena thermophila as a consumer and the bacterium Escherichia coli as a decomposer. Effects of aluminum and copper on the microcosm were investigated in this study, while effects of {gamma}-rays, ultraviolet radiation, acidification, manganese, nickel and gadolinium were reported in previous studies. The microcosm could detect not only the direct effects of these agents but also the community-level effects due to the interspecies interactions or the interactions between organisms and toxic agents. The authors evaluated doses or concentrations of each toxic agent which had the following effects on the microcosm: (1) no effects; (2) recognizable effects, i.e., decrease or increase in the cell densities of at least one species; (3) severe effects, i.e., extinction of one or two species; and (4) destructive effects, i.e., extinction of all species. The resulting effects data will contribute to an ecological risk assessment of the toxic agents compared with acute doses of ionizing radiation.

  15. Acute toxicity effects of Prunus avium fruit extract and selection of optimum dose against radiation exposure.

    Science.gov (United States)

    Sisodia, Rashmi; Sharma, K; Singh, Smita

    2009-01-01

    The objective of the study was to evaluate the acute toxicity of different doses of the methanolic extract of the fruit pulp of Prunus avium (family Rosaceae), which is used ethno-medicinally for the treatment of various diseases, and to find out the optimal dose of Prunus avium extract against 10 Gy gamma-radiation exposure. To test acute toxicity in mice, different doses of PAE (Prunus avium fruit extract) were given orally for 15 consecutive days, after which the animals were observed for another 15 days; the LD50/15 of the methanolic extract was calculated to be 4.947 gm/kg body weight (b.wt). In optimum dose selection against radiation exposure, oral administration of 450 mg/kg b.wt/d of PAE for 15 consecutive days before exposure to 10 Gy of gamma-radiation was found to afford maximum protection in terms of body weight and survivability of the mice in comparison to other doses.

  16. Low-dose radiation modifies skin response to acute gamma-rays and protons.

    Science.gov (United States)

    Mao, Xiao Wen; Pecaut, Michael J; Cao, Jeffrey D; Moldovan, Maria; Gridley, Daila S

    2013-01-01

    The goal of the present study was to obtain pilot data on the effects of protracted low-dose/low-dose-rate (LDR) γ-rays on the skin, both with and without acute gamma or proton irradiation (IR). Six groups of C57BL/6 mice were examined: a) 0 Gy control, b) LDR, c) Gamma, d) LDR+Gamma, e) Proton, and f) LDR+Proton. LDR radiation was delivered to a total dose of 0.01 Gy (0.03 cGy/h), whereas the Gamma and Proton groups received 2 Gy (0.9 Gy/min and 1.0 Gy/min, respectively). Assays were performed 56 days after exposure. Skin samples from all irradiated groups had activated caspase-3, indicative of apoptosis. The significant (pGamma and Proton groups were not present when LDR pre-exposure was included. However, the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay for DNA fragmentation and histological examination of hematoxylin and eosin-stained sections revealed no significant differences among groups, regardless of radiation regimen. The data demonstrate that caspase-3 activation initially triggered by both forms of acute radiation was greatly elevated in the skin nearly two months after whole-body exposure. In addition, LDR γ-ray priming ameliorated this response.

  17. Reduction of acute toxicity of the pharmaceutical fluoxetine (Prozac) submitted to ionizing radiation to Vibrio fischeri

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Dymes R.A.; Garcia, Vanessa S.G.; Vilarrubia, Anna C.S.; Borrely, Sueli I., E-mail: vanessagarcia@usp.br, E-mail: sborrely@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    The constant use of pharmaceutical drugs by great part of the population and its continuous input into the environment creates a growing need of investigating its presence, behavior and the effects on aquatic biota, as well as new ways to treat wastewater containing such substances. The fluoxetine hydrochloride (FH) present in the drug Prozac is an active ingredient used in the treatment of depressive and anxiety disorders. Generally, these compounds enter the aquatic environment by sewage collectors systems after undergoing prior treatment in sewage treatment plants (STPs) or without any treatment. This study focused on evaluating the reduction of acute toxicity of the pharmaceutical FH, under its manipulated formula, for the marine bacterium Vibrio fischeri. It was also evaluated the acute toxicity of the aqueous solution containing the FH after its exposition to ionizing radiation from industrial electron accelerator. It was performed acute toxicity tests lasting 15 minutes, where the average EC (50) of the non-irradiated CF water solution was approximately 0.68 mg L-1. While the CF water solution irradiated with 1 kGy, 2.5 kGy, 7.5 kGy and 10 kGy, presented an average EC(50) 1.63 mg.L{sup -1}, 2.34 mg.L{sup -1}, 2.35 mg.L{sup -1} and 1.80 mg.L{sup -1}, respectively, showing a notable reduction of the acute toxicity for this organism. (author)

  18. Effect of BMPs on hematopoietic injury of acute radiation sickness in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tian Qiong; Zhang Shaozhang; Pu Qin; Zhang Fake [Fourth Military Medical University, Xi' an Shaanxi (China); Hannah, X.H. [Department of Biochemistry, Hong Kong Science and Technology, Hong Kong (China)

    2000-05-01

    The purpose of this paper is to investigate the effect of Bone morphogenetic proteins (BMPs) on hematopoietic acute radiation sickness in mice. BMP, rhBMP-2m and PBK/hBMP-2-NIH3T3 cells were obtained separately by chemistry, molecule biological method and genetherapy method. In this study, the effect of BMPs on hematopoiesis was detected at postirradiation: some hematological parameters, 30 days the survival ratio and formation of bone marrow CFU-GM colony. The experiments indicate that when phBMP (purified bovine bone morphogenetic protein) can increase the formation of bone narrow CFU-GM colony (p<0.05) at 10th d after irradiation. Irradiation control group's mice died in 30 days, but effect of rhBMP-2m on the survival of mice after 7.5Gy irradiation, was detected whereas there were 10%, 15% and 35% all mice of survived after injection i.p. with 0.5 mg, 1.0 mg and 2.0 mg of rhBMP-2m respectively. All hematological parameters of treated mice were significantly higher than control group (p<0.01). PBK/hBMP-2-NIH3T3 cells were established and transplanted into mice irradiated by 7.0Gy r ray by i.p., the survival ratio of treated mice higher than negative control group (p<0.01), and all hematopoietic parameters were increased statistically significant (p<0.01). These data support the our hypothesis: BMPs can treat the acute radiation sickness. The results indicate that in adult mice, BMPs can recover or treat the hematopoietic injury of acute radiation sickness in mice. (author)

  19. Acute limb ischemia secondary to radiation-induced arteritis: case report

    Directory of Open Access Journals (Sweden)

    Jose Emerson dos Santos Souza

    2013-09-01

    Full Text Available Radiation-induced arteritis is a rare but well-known complication of radiotherapy. This report describes the case of a 34-year-old woman with uterine cervical cancer who was diagnosed with left iliofemoral deep vein thrombosis (DVT 2 years after radiotherapy, and 2 months later, during the treatment of DVT with effective anticoagulation, developed an episode of acute arterial ischemia of the left lower limb secondary to a long subocclusive lesion of the external iliac artery. The patient was treated with angioplasty and stenting of the lesion and recovered uneventfully after the endovascular procedure.

  20. Cytogenetic effects of acute gamma radiation on leaf and apical meristem of scotch pine

    Energy Technology Data Exchange (ETDEWEB)

    Tikhomirov, F.A.; Fedotov, I.S.; Prister, B.S.; Remezova, M.M.

    1977-01-01

    A study was made of the effect of acute ..gamma..-radiation on incidence of chromosomal aberrations in apical and leaf meristem of the pine in the first and second postradiation vegetation periods. It was found that the radiosensitivity of these tissues is the same. In the second postradiation vegetation period, after exposure to a dosage of 1500-2500 rad, there is normalization of the parameters studied. Restitution of tissues can occur both as a result of recovery of involved meristem cells and by means of differentiation of subapical meristem cells.

  1. Diagnostic value of 18F-FDG uptake by spleen in acute radiation disease

    Directory of Open Access Journals (Sweden)

    Shao-jie WU

    2015-07-01

    Full Text Available Objective To investigate whether 18F-FDG uptake can be applied in dosimetry to facilitate a rapid and accurate evaluation of individual radiation dosage after a nuclear accident. Methods Forty-eight Tibetan minipigs were randomly assigned into 6 groups, i.e., 0, 1, 2, 5, 8 and 11Gy groups. Animals in all except 0Gy group received total body irradiation (TBI with a 8MV X centrifugal linear accelerator, and 18F-FDG combined positron-emission tomography and computed tomography (PET/CT were carried out before TBI, and also at 6, 24 and 72h after receiving TBI in different doses ranging from 1 to 11Gy. Spleen tissues and blood samples were collected for histological examination, apoptosis, and routine blood analysis. Results Mean standardized uptake values (SUVs of the spleen showed significant differences between experimental groups and control group. The spleen SUVs at 6h post-irradiation showed significant correlation with radiation dose; Spearman's correlation coefficient was 0.95(P<0.01. Histopathological observations showed that the degree of splenic damage was proportional to the radiation dose. Moreover, flow cytometry revealed that apoptosis was one of the major forms of splenic lymphocyte death. Conclusion In the Tibetan minipig model, it was shown that radiation doses bear a close relationship with the 18F-FDG uptake of spleen. This finding suggests that 18F-FDG PET/CT may be useful for the rapid detection of individual radiation dosage after acute radiation disease (ARD. DOI: 10.11855/j.issn.0577-7402.2015.07.08

  2. Protective effect of vitamin A on acute radiation injury in the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Beyzadeoglu, Murat; Balkan, Mujdat; Demiriz, Murat; Dirican, Bahar; Oner, Koksal; Pak, Yucel [Gulhane Military Medical Academy, Ankara (Turkey); Tibet, Hasan

    1997-01-01

    The objective of this study was to examine the influence of vitamin A on the development of early radiation-induced reactions in the rat small intestine. The early effects of intraoperative gamma-radiation on the small bowel utilizing the terminal ileum of Sprague-Dawley rats and the protective effect of supplemental vitamin A on acute radiation injury were investigated. Three groups were included in the study: group I (10 rats) was the surgical control group; group II (13 rats) underwent only intraoperative irradiation; and group III (10 rats) was the vitamin A plus irradiation group. Exteriorized terminal ileal segments of groups II and III were exposed to a single fraction of 20 Gy of intraoperative gamma-irradiation. On the seventh postoperative day, terminal ileal segments of all rats were resected and histopathologically evaluated for ulceration, enteritis cystica profunda, atypical epithelial regeneration, fibrosis, vascular sclerosis, and inflammatory process. Although none of the above findings were present in the surgical control group, group III rats experienced less severe effects than group II rats. The results suggest the early side effects of radiation may be prevented by vitamin A supplementation. (author)

  3. Acutely exacerbated hypertension and increased inflammatory signs due to radiation treatment for metastatic pheochromocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Teno, Shinichi; Tanabe, Akiyo; Nomura, Kaoru; Demura, Hiroshi [Tokyo Women`s Medical Coll. (Japan)

    1996-10-01

    Hypertension and norepinephrine hypersecretion in a 59-year-old woman suffering from malignant pheochromocytoma with multiple metastases were appropriately controlled with {alpha}- and {beta}- blockers, and {alpha}-methyltyrosine ({alpha}-MT), a catecholamine-synthesis inhibitor. Metastasized vertebrae were treated with external radiation to relieve pain, but this treatment had to be interrupted at a total dose of 20 Gy because the patient suffered acutely exacerbated hypertension (200/110 mmHg), tachycardia (160 beats/min) and a low-grade fever. Simultaneously her serum levels of LDH, potassium, urea nitrogen, creatinine, white blood cell count, CRP and norepinephrine were significantly increased, suggesting that this episode was due to radiation-induced tissue destruction and the leakage of catecholamines and possibly interleukin-6, a cytokine mediating inflammation which is reportedly present in pheochromocytoma. The marked hypertension was controlled by continuous iv administration of phentolamine and propranolol. Although radiation therapy effectively relieves pain due to neoplasmic metastasis to the bone, physicians should be aware that life-threatening complications such as the above occur in malignant pheochromocytoma. Sufficient pretreatment with adrenergic blocking agents and/or {alpha}-MT and careful monitoring of the patient`s general condition during radiation therapy, even at a low dose, are highly recommended. (author)

  4. Initial symptoms of acute radiation syndrome in the JCO criticality accident in Tokai-mura.

    Science.gov (United States)

    Akashi, M; Hirama, T; Tanosaki, S; Kuroiwa, N; Nakagawa, K; Tsuji, H; Kato, H; Yamada, S; Kamata, T; Kinugasa, T; Ariga, H; Maekawa, K; Suzuki, G; Tsujii, H

    2001-09-01

    A criticality accident occurred on September 30, 1999, at the uranium conversion plant in Tokai-mura (Tokai-village), Ibaraki Prefecture, Japan. When the criticality occurred, three workers saw a "blue-white glow," and a radiation monitor alarm was sounded. They were severely exposed to neutron and gamma-ray irradiation, and subsequently developed acute radiation syndrome (ARS). One worker reported vomiting within minutes and loss of consciousness for 10-20 seconds. This worker also had diarrhea an hour after the exposure. The other worker started to vomit almost an hour after the exposure. The three workers, including their supervisor, who had no symptoms at the time, were brought to the National Mito Hospital by ambulance. Because of the detection of gamma-rays from their body surface by preliminary surveys and decreased numbers of lymphocytes in peripheral blood, they were transferred to the National Institute of Radiological Sciences (NIRS), which has been designated as a hospital responsible for radiation emergencies. Dose estimations for the three workers were performed by prodromal symptoms, serial changes of lymphocyte numbers, chromosomal analysis, and 24Na activity. The results obtained from these methods were fairly consistent. Most of the data, such as the dose rate of radiation, its distribution, and the quality needed to evaluate the average dose, were not available when the decision for hematopoitic stem cell transplantation had to be made. Therefore, prodromal symptoms may be important in making decisions for therapeutic strategies, such as stem-cell transplantation in heavily exposed victims.

  5. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); EMR3738, Université Lyon 1, Lyon (France); Decullier, Evelyne; Bin, Sylvie [Pole Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon (France); Université Lyon 1, Lyon (France); EA SIS, Université de Lyon, Lyon (France); Faix, Antoine [Department of Urology, Clinique Beausoleil, Montpellier (France); Ruffion, Alain [Université Lyon 1, Lyon (France); Department of Urology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Jalade, Patrice [Department of Medical Physics, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Fenoglietto, Pascal [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France); Udrescu, Corina; Enachescu, Ciprian [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Azria, David [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France)

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  6. Comparison of acute and subacute genitourinary and gastrointestinal adverse events of radiotherapy for prostate cancer using intensity-modulated radiation therapy, three-dimensional conformal radiation therapy, permanent implant brachytherapy and high-dose-rate brachytherapy

    NARCIS (Netherlands)

    Morimoto, Masahiro; Yoshioka, Yasuo; Konishi, Koji; Isohashi, Fumiaki; Takahashi, Yutaka; Ogata, Toshiyuki; Koizumi, Masahiko; Teshima, Teruki; Bijl, Henk P; van der Schaaf, Arjen; Langendijk, Johannes A; Ogawa, Kazuhiko

    2014-01-01

    AIMS AND BACKGROUND: To examine acute and subacute urinary and rectal toxicity in patients with localized prostate cancer monotherapeutically treated with the following four radiotherapeutic techniques: intensity-modulated radiation therapy, three-dimensional conformal radiation therapy,

  7. Countermeasure development : Specific Immunoprophylaxis and Immunotherapy of Combined Acute Radiation Syndromes.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava

    Introduction: Combined Acute Radiation Syndromes (CARS) are extremely severe injuries. Combination of Radiation and Thermal factors induce development of the acute pathologi-cal processes in irradiated mammals: systemic inflammatory response syndrome (SIRS), toxic multiple organ injury (TMOI), toxic multiple organ dysfunction syndromes (TMOD), toxic multiple organ failure (TMOF). Also, high doses of Radiation and Thermal injury induce for-mation of following Toxin groups: A. Specific Radiation Toxins; B. Specific Thermal Toxins; C. Nonspecific Histiogenic Pro-inflammatory and Inflammatory Toxins (NHIT). Specific Radi-ation Toxins (SRT) include four major group of Toxins: Cerebrovascular Radiation Toxins (Cv RT), Cardiovascular Radiation Toxins (Cr RT), Gastrointestinal Radiation Toxins (Gi RT), and Hematopoietic Radiation Toxins (Hp RT). CvRT, Cr RT, Gi RT groups of toxins are defined as Neurotoxins and Hp RT group is defined as Hematotoxins. Specific Thermal Toxins (STT) were isolated from the burned skin (Voul S., Colker I. 1972). The group of Nonspecific Histio-genic Inflammatory Toxins (NHIT) includes high amount of tissue toxins which are peptides with medium molecular weight. This group of polypeptides can be a significant factor as a part of developing of the general inflammation reaction. However, NHIT toxins can't induce many reactions and changes which are specific for radiation. Specific Radiation Toxins (SRT) can induce specific processes and reactions such as clonogenic cell death -programmed apoptotic necrosis. Although besides high doses of radiation, other forms of cell death such as Pyroptosis or Oncosis should be considered. We postulate that NHIT toxins are similar for high doses of radiation and thermal injury. Specific Radiation Toxins (SRT) are induced by high doses of radiation. Specific Thermal Toxins (STT) toxins which formation is induced by a Thermal Factor are different from SRT. Administration of STT toxins or NHIT toxins (IV or IM) to

  8. Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

    Science.gov (United States)

    Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

    2016-01-01

    Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

  9. Genetic risk score and acute skin toxicity after breast radiation therapy.

    Science.gov (United States)

    Borghini, Andrea; Vecoli, Cecilia; Mercuri, Antonella; Petruzzelli, Maria Fonte; D'Errico, Maria Patrizia; Portaluri, Maurizio; Andreassi, Maria Grazia

    2014-09-01

    Genetic predisposition has been shown to affect the severity of skin complications in breast cancer patients after radiotherapy. Limited data exist regarding the use of a genetic risk score (GRS) for predicting risk of tissue radiosensitivity. We evaluated the impact of different single-nucleotide polymorphisms (SNPs) in genes related to DNA repair mechanisms and oxidative stress response combined in a GRS on acute adverse effects induced by breast radiation therapy (RT). Skin toxicity was scored according to the Radiation Therapy Oncology Group (RTOG) criteria in 59 breast cancer patients who received RT. After genotyping, a multilocus GRS was constructed by summing the number of risk alleles. The hazard ratio (HR) for GSTM1 was 2.4 (95% confidence intervals [CI]=1.1-5.3, p=0.04). The other polymorphisms were associated to an increased adverse radiosensitivity, although they did not reach statistical significance. GRS predicted roughly 40% risk for acute skin toxicity per risk allele (HR 1.37, 95% CI=1.1-1.76, pskin reaction (HR 5.1, 95% CI=1.2-22.8, p=0.03). Our findings demonstrate that the joint effect of SNPs from oxidative stress and DNA damage repair genes may be a promising approach to identify patients with a high risk of skin reaction after breast RT.

  10. Pneumonitis associated with occult heartworm disease in dogs.

    Science.gov (United States)

    Calvert, C A; Losonsky, J M

    1985-05-15

    Nine of 69 dogs with occult heartworm disease (13%) had allergic pneumonitis characterized by consistent clinical and radiographic signs. Although the clinical signs were severe, the degree of radiographic pulmonary arterial abnormalities was mild. Corticosteroid therapy resulted in rapid resolution of clinical and radiographic signs; thiacetarsamide therapy was then given without complications. This syndrome may not be recognized as heartworm-associated and may be confused with other disorders, some being associated with a poor prognosis and requiring different therapy.

  11. Spotlight on the diagnosis of extrinsic allergic alveolitis (hypersensitivity pneumonitis).

    Science.gov (United States)

    Baur, Xaver; Fischer, Axel; Budnik, Lygia T

    2015-01-01

    Repeated inhalative exposures to antigenic material from a variety of sources, mainly from moulds, thermophilic Actinomycetes, and avians, respectively, can induce immune responses with the clinical picture of extrinsic allergic alveolitis (EAA) or hypersensitivity pneumonitis. Delays of years or even decades till the diagnosis is made are not uncommon; frequent misdiagnoses include allergic asthma, COPD, recurrent flue and other infections. We provide here the state of the art references, a detailed case description and recommend a current diagnostics schema.

  12. Sauna lung: hypersensitivity pneumonitis due to Exophiala jeanselmei.

    Science.gov (United States)

    Huang, Wei-Chen; Lu, Yin-Hsiu; Lin, Zih-Gong; Su, Wen-Lin

    2010-04-01

    A 55-year-old man developed progressive cough and dyspnoea after regular attendance at a public steam bath. Hypoxaemia, diffuse pulmonary infiltrates and a predominance of lymphocytes with an increased percentage of CD8+ T cells in his bronchoalveolar lavage fluid suggested hypersensitivity pneumonitis. Microbial cultures from the steam bath room and tank identified Exophiala jeanselmei. Immunoblotting assays from the patient's serum confirmed the major antigenic stimulus. The patient recovered fully after systemic corticosteroid treatment and cessation of further exposure.

  13. Chronic pneumonitis of infancy: high-resolution CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, Oeystein E.; Owens, Catherine M. [Radiology Department, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, WC1N 3JH, London (United Kingdom); Sebire, Neil J. [Histopathology Department, Great Ormond Street Hospital for Children NHS Trust, London (United Kingdom); Jaffe, Adam [Portex Respiratory Medicine Unit, The Institute of Child Health, University College London, London (United Kingdom)

    2004-01-01

    Chronic pneumonitis of infancy (CPI) is a very rare entity. We report the chest radiography and high-resolution CT (HRCT) findings in an infant with histopathologically confirmed CPI. The child was admitted for intensive care 18 h after birth and died at 39 days of age. On HRCT there was diffuse ground-glass change, interlobular septal thickening and discrete centrilobular nodules. An accurate diagnosis is crucial for correct management; however, several entities with the same HRCT findings are recognized. (orig.)

  14. Working with argan cake: a new etiology for hypersensitivity pneumonitis

    OpenAIRE

    Paris, Christophe; Herin, Fabrice; Reboux, Gabriel; Penven, Emmanuelle; Barrera, Coralie; Guidat, Cécile; Thaon, Isabelle

    2015-01-01

    Background Argan is now used worldwide in numerous cosmetic products. Nine workers from a cosmetic factory were examined in our occupational medicine department, following the diagnosis of a case of hypersensitivity pneumonitis (HP) related to handling of argan cakes. Methods Operators were exposed to three forms of argan (crude granulates, powder or liquid) depending on the step of the process. All workers systematically completed standardized questionnaires on occupational and medical histo...

  15. A Case of Occupational Hypersensitivity Pneumonitis Associated with Trichloroethylene

    OpenAIRE

    Kim, Young Jae; Hwang, Eu Dong; Leem, Ah Young; Kang, Beo Deul; Chang, Soo Yun; Kim, Ho Keun; Park, In Kyu; Kim, Song Yee; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Park, Moo Suk; Kim, Young Sam; Kim, Se Kyu; Chang, Joon

    2014-01-01

    Trichloroethylene (TCE) is a toxic chemical commonly used as a degreasing agent, and it is usually found in a colorless or blue liquid form. TCE has a sweet, chloroform-like odor, and this volatile chlorinated organic chemical can cause toxic hepatitis, neurophysiological disorders, skin disorders, and hypersensitivity syndromes. However, the hypersensitivity pneumonitis (HP) attributed to TCE has rarely been reported. We hereby describe a case of HP associated with TCE in a 29-year-old man w...

  16. Medical Management of Acute Radiation Syndromes : Comparison of Antiradiation Vaccine and Antioxidants radioprotection potency.

    Science.gov (United States)

    Maliev, Slava; Popov, Dmitri; Lisenkov, Nikolai

    Introduction: This experimental study of biological effects of the Antiradiation Vaccine and Antioxidants which were used for prophylaxis and treatment of the Acute Radiation Syndromes caused by high doses of the low-LET radiation. An important role of Reactive Oxyden Species (Singlet oxygen, hydroxyl radicals, superoxide anions and bio-radicals)in development of the Acute Radiation Syndromes could be defined as a "central dogma" of radiobiology. Oxida-tion and damages of lipids, proteins, DNA, and RNA are playing active role in development of postradiation apoptosis. However, the therapeutic role of antioxidants in modification of a postradiation injury caused by high doses of radiation remains controversial.Previous stud-ies had revealed that antioxidants did not increase a survival rate of mammals with severe forms of the Acute Radiation Syndromes caused by High Doses of the low-LET radiation. The Antiradiation Vaccine(ARV) contains toxoid forms of the Radiation Toxins(RT) from the Specific Radiation Determinants Group (SRD). The RT SRD has toxic and antigenic prop-erties at the same time and stimulates a specific antibody elaboration and humoral response form activated acquired immune system. The blocking antiradiation antibodies induce an im-munologically specific effect and have inhibiting effects on radiation induced neuro-toxicity, vascular-toxicity, gastrointestinal toxcity, hematopoietic toxicity, and radiation induced cytol-ysis of selected groups of cells that are sensitive to radiation. Methods and materials: Scheme of experiments: 1. Irradiated animals with development of Cerebrovascular ARS (Cv-ARS), Cardiovascular ARS (Cr-ARS) Gastrointestinal ARS(GI-ARS), Hematopoietic ARS (H-ARS) -control -were treated with placebo administration. 2. Irradiated animals were treated with antioxidants prophylaxisis and treatment of Cv-ARS, Cr-SRS, GI-ARS, Hp-ARS forms of the ARS. 3. irradiated animals were treated with radioprotection by Antiradiation Vaccine

  17. Therapy and prophylaxis of acute and late radiation-induced sequelae of the esophagus

    Energy Technology Data Exchange (ETDEWEB)

    Zimmermann, F.B.; Geinitz, H.; Feldmann, H.J. [Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, Muenchen (Germany)

    1998-11-01

    Background: Radiation-induced esophagitis is a frequent acute side effect in curative and palliative radiotherapy of thoracal and cervical tumors. Late reactions are rare but might be severe. Methods: A resarch for reports on prophylactic and supportive therapies of radiation-induced esophagitis was performed (Medline, Cancerlit, and others). Results: Nutrition must be ensured and symptomatic relief of sequelae is important, especially in the case of dysphagia. The latter can be improved by topic or systemic analgetics. If esophageal spasm occurs, calcium antagonists might help. In case of gastro-esophageal reflux proton pump inhibitors should be used. There is no effective prophylactic measure for radiation esophagitis. Late side effects with clinical relevance are rare in conventional radiotherapy. Chronic ulcera, fistula or stenosis may develop. Before any treatment, a tumor infiltration of the esophagus should be excluded by biopsy. This can lead more often to late complications than radiation therapy itself. Nutrition should be ensured by endoscopic dilation, stent-implantation, or endoscopic percutaneous gastrostomy. Local injection of steroids might be used to avoid an early restenosis. Conclusions: An intensive symptomatic therapy of acute esophagitis is reasonable. Effective prophylaxis do not exist. Late radiation induced sequelae is rare. Therefore, a tumor recurrenc e should be excluded in cases of dysphagia. Securing nutrition by PEG, stent, or port is well in the fore. (orig.) [Deutsch] Hintergrund: Die radiogene Oesophagitis ist eine haeufige akute Nebenwirkung bei kurativen wie palliativen Bestrahlungen thorakaler und zervikaler Tumoren. Spaete Gewebereaktionen sind selten, koennen aber schwerwiegend sein. Methode: Es wurde eine Literaturrecherche nach prophylaktischen und supportiven Therapien der radiogen verursachten Oesophagitis durchgefuehrt (Medline, Cancerlit und andere). Ergebnisse: Therapeutisch stehen die Sicherung der Ernaehrung und die

  18. Protective effects of caffeic acid phenethyl ester against acute radiation-induced hepatic injury in rats.

    Science.gov (United States)

    Chu, JianJun; Zhang, Xiaojun; Jin, Liugen; Chen, Junliang; Du, Bin; Pang, Qingfeng

    2015-03-01

    Caffeic acid phenyl ester (CAPE) is a potent anti-inflammatory agent and it can eliminate the free radicals. The current study was intended to evaluate the protective effect of CAPE against the acute radiation-induced liver damage in rats. Male Sprague-Dawley rats were intraperitoneally administered with CAPE (30 mg/kg) for 3 consecutive days before exposing them to a single dose of 30 Gy of β-ray irradiation to upper abdomen. We found that pretreatment with CAPE significantly decreased the serum levels of alanine aminotransferase and aspartate aminotransferase and increased the activity of superoxide dismutase and glutathione. Histological evaluation further confirmed the protection of CAPE against radiation-induced hepatotoxicity. TUNEL assay showed that CAPE pretreatment inhibited hepatocyte apoptosis. Moreover, CAPE inhibited the nuclear transport of NF-κB p65 subunit, decreased the level of tumor necrosis factor-α, nitric oxide and inducible nitric oxide synthase. Taken together, these results suggest that pretreatment with CAPE offers protection against radiation-induced hepatic injury.

  19. Thyroid disorders in acute period after radiation therapy on neck region

    Directory of Open Access Journals (Sweden)

    E I Bobrova

    2015-06-01

    Full Text Available Aim. The aim of our study was to analyze thyroid status in adult patients with Hodgkin’s lymphoma in acute period after radiotherapy on neck region. Material and methods. Thyroid function (TSH, free T 4, anti-TPO and thyroid ultrasound were evaluated in 22 adults (10 women, 12 men, mean age 30.2 yrs with a history of Hodgkin’s lymphoma (HL before radiotherapy on neck region, 7-14 days, 6 month, 1 year after treatment. Results. Incidence of subclinical hyperthyroidism was 13.6% in acute period (7-14 days after radiotherapy on neck region. There was correlation between dose of radiation and incidence of acute thyroiditis ( r = 0.67, p = 0.03. TSH level fall directly after treatment (1.08 vs 1.88 mkMEd/l р = 0.03, but 6 month after this difference disappeared. T 4 free level decreased 1 yr after treatment (1.18 vs 0.99 ng/ml in compare with measurement before treatment ( p = 0,01. Thyroid volume decreased (9.8 ml vs 5.7 ml 6 month after radiotherapy in compare with measurement before treatment ( p = 0.03, and keep on decreasing 1 yr after treatment (5.35 vs 9.7 ml p = 0.003. Conclusions. These data indicate that some patients with HL receiving high dose of radiotherapy on neck region can develop acute thyroiditis, but this abnormalities are transitory and do not reviewed treatment.

  20. 2013 Space Radiation Standing Review Panel Status Review for: The Risk of Acute and Late Central Nervous System Effects from Radiation Exposure, The Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs), The Risk Of Degenerative Tissue Or Other Health Effects From Radiation Exposure, and The Risk of Radiation Carcinogenesis

    Science.gov (United States)

    2014-01-01

    The Space Radiation Standing Review Panel (from here on referred to as the SRP) was impressed with the strong research program presented by the scientists and staff associated with NASA's Space Radiation Program Element and National Space Biomedical Research Institute (NSBRI). The presentations given on-site and the reports of ongoing research that were provided in advance indicated the potential Risk of Acute and Late Central Nervous System Effects from Radiation Exposure (CNS) and were extensively discussed by the SRP. This new data leads the SRP to recommend that a higher priority should be placed on research designed to identify and understand these risks at the mechanistic level. To support this effort the SRP feels that a shift of emphasis from Acute Radiation Syndromes (ARS) and carcinogenesis to CNS-related endpoints is justified at this point. However, these research efforts need to focus on mechanisms, should follow pace with advances in the field of CNS in general and should consider the specific comments and suggestions made by the SRP as outlined below. The SRP further recommends that the Space Radiation Program Element continue with its efforts to fill the vacant positions (Element Scientist, CNS Risk Discipline Lead) as soon as possible. The SRP also strongly recommends that NASA should continue the NASA Space Radiation Summer School. In addition to these broad recommendations, there are specific comments/recommendations noted for each risk, described in detail below.

  1. Clinical outcome and predictors of survival and pneumonitis after stereotactic ablative radiotherapy for stage I non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Chang Joe Y

    2012-09-01

    Full Text Available Abstract Background Stereotactic ablative radiotherapy (SABR can achieve excellent local control rates in early-stage non-small cell lung cancer (NSCLC and has emerged as a standard treatment option for patients who cannot undergo surgery or those with isolated recurrences. However, factors that may predict toxicity or survival are largely unknown. We sought here to identify predictors of survival and pneumonitis after SABR for NSCLC in a relatively large single-institution series. Methods Subjects were 130 patients with stage I NSCLC treated with four-dimensional computed tomography (4D CT –planned, on-board volumetric image–guided SABR to 50 Gy in 4 fractions. Disease was staged by positron emission tomography/computed tomography (PET/CT and scans were obtained again at the second follow-up after SABR. Results At a median follow-up time of 26 months, the 2-year local control rate was 98.5%. The median overall survival (OS time was 60 months, and OS rates were 93.0% at 1 year, 78.2% at 2 years, and 65.3% at 3 years. No patient experienced grade 4–5 toxicity; 15 had radiation pneumonitis (12 [9.3%] grade 2 and 3 [2.3%] grade 3. Performance status, standardized uptake value (SUVmax on staging PET/CT, tumor histology, and disease operability were associated with OS on univariate analysis, but only staging SUVmax was independently predictive on multivariate analysis (P = 0.034. Dosimetric factors were associated with radiation pneumonitis on univariate analysis, but only mean ipsilateral lung dose ≥9.14 Gy was significant on multivariate analysis (P = 0.005. Conclusions OS and radiation pneumonitis after SABR for stage I NSCLC can be predicted by staging PET SUVmax and ipsilateral mean lung dose, respectively.

  2. Autologous bone marrow stromal cell transplantation as a treatment for acute radiation enteritis induced by a moderate dose of radiation in dogs.

    Science.gov (United States)

    Xu, Wenda; Chen, Jiang; Liu, Xu; Li, Hongyu; Qi, Xingshun; Guo, Xiaozhong

    2016-05-01

    Radiation enteritis is one of the most common complications of cancer radiotherapy, and the development of new and effective measures for its prevention and treatment is of great importance. Adult bone marrow stromal stem cells (ABMSCs) are capable of self-renewal and exhibit low immunogenicity. In this study, we investigated ABMSC transplantation as a treatment for acute radiation enteritis. We developed a dog model of acute radiation enteritis using abdominal intensity-modulated radiation therapy in a single X-ray dose of 14 Gy. ABMSCs were cultured in vitro, identified via immunofluorescence and flow cytometry, and double labeled with CM-Dil and superparamagnetic iron oxide (SPIO) before transplantation, which took place 48 hours after abdominal irradiation in a single fraction. The dog model of acute radiation enteritis was transplanted with cultured ABMSCs labeled with CM-Dil and SPIO into the mesenteric artery through the femoral artery. Compared with untreated control groups, dogs treated with ABMSCs exhibited substantially longer survival time and improved relief of clinical symptoms. ABMSC transplantation induced the regeneration of the intestinal epithelium and the recovery of intestinal function. Furthermore, ABMSC transplantation resulted in elevated serum levels of the anti-inflammatory cytokine interleukin-11 (IL10) and intestinal radioprotective factors, such as keratinocyte growth factor, basic fibroblast growth factor-2, and platelet-derived growth factor-B while reducing the serum level of the inflammatory cytokine IL17. ABMSCs induced the regeneration of the intestinal epithelium and regulated the secretion of serum cytokines and the expression of radioprotective proteins and thus could be beneficial in the development of novel and effective mitigators of and protectors against acute radiation enteritis.

  3. Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Daila S. Gridley, PhD

    2012-03-30

    FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findings remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide information

  4. Feasibility and Acute Toxicity of Hypofractionated Radiation in Large-breasted Patients

    Energy Technology Data Exchange (ETDEWEB)

    Dorn, Paige L., E-mail: pdorn@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Chicago, IL (United States); Corbin, Kimberly S.; Al-Hallaq, Hania; Hasan, Yasmin; Chmura, Steven J. [Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Chicago, IL (United States)

    2012-05-01

    Purpose: To determine the feasibility of and acute toxicity associated with hypofractionated whole breast radiation (HypoRT) after breast-conserving surgery in patients excluded from or underrepresented in randomized trials comparing HypoRT with conventional fractionation schedules. Methods and Materials: A review was conducted of all patients consecutively treated with HypoRT at University of Chicago. All patients were treated to 42.56 Gy in 2.66 Gy daily fractions in either the prone or supine position. Planning was performed in most cases using wedges and large segments or a 'field-in-field' technique. Breast volume was estimated using volumetric measurements of the planning target volume (PTV). Dosimetric parameters of heterogeneity (V105, V107, V110, and maximum dose) were recorded for each treatment plan. Acute toxicity was scored for each treated breast. Results: Between 2006 and 2010, 78 patients were treated to 80 breasts using HypoRT. Most women were overweight or obese (78.7%), with a median body mass index of 29.2 kg/m{sup 2}. Median breast volume was 1,351 mL. Of the 80 treated breasts, the maximum acute skin toxicity was mild erythema or hyperpigmentation in 70.0% (56/80), dry desquamation in 21.25% (17/80), and focal moist desquamation in 8.75% (7/80). Maximum acute toxicity occurred after the completion of radiation in 31.9% of patients. Separation >25 cm was not associated with increased toxicity. Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (p = 0.01). Patients with breast volume >2,500 mL experienced focal moist desquamation in 27.2% of cases compared with 6.34% in patients with breast volume <2,500 mL (p = 0.03). Conclusions: HypoRT is feasible and safe in patients with separation >25 cm and in patients with large breast volume when employing modern planning and positioning techniques. We recommend counseling regarding expected increases in skin toxicity in women

  5. γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status

    Directory of Open Access Journals (Sweden)

    Vijay K. Singh

    2016-05-01

    Full Text Available The hazard of ionizing radiation exposure due to nuclear accidents or terrorist attacks is ever increasing. Despite decades of research, still, there is a shortage of non-toxic, safe and effective medical countermeasures for radiological and nuclear emergency. To date, the U.S. Food and Drug Administration (U.S. FDA has approved only two growth factors, Neupogen (granulocyte colony-stimulating factor (G-CSF, filgrastim and Neulasta (PEGylated G-CSF, pegfilgrastim for the treatment of hematopoietic acute radiation syndrome (H-ARS following the Animal Efficacy Rule. Promising radioprotective efficacy results of γ-tocotrienol (GT3; a member of the vitamin E family in the mouse model encouraged its further evaluation in the nonhuman primate (NHP model. These studies demonstrated that GT3 significantly aided the recovery of radiation-induced neutropenia and thrombocytopenia compared to the vehicle controls; these results particularly significant after exposure to 5.8 or 6.5 Gray (Gy whole body γ-irradiation. The stimulatory effect of GT3 on neutrophils and thrombocytes (platelets was directly and positively correlated with dose; a 75 mg/kg dose was more effective compared to 37.5 mg/kg. GT3 was also effective against 6.5 Gy whole body γ-irradiation for improving neutrophils and thrombocytes. Moreover, a single administration of GT3 without any supportive care was equivalent, in terms of improving hematopoietic recovery, to multiple doses of Neupogen and two doses of Neulasta with full supportive care (including blood products in the NHP model. GT3 may serve as an ultimate radioprotector for use in humans, particularly for military personnel and first responders. In brief, GT3 is a promising radiation countermeasure that ought to be further developed for U.S. FDA approval for the ARS indication.

  6. Radiological and Nuclear Emergencies: Medical Management of Radiation Injuries

    Directory of Open Access Journals (Sweden)

    L. Ravi Shankar

    2011-02-01

    Full Text Available Nuclear radiation which could be in the form of alpha, beta, gamma rays, etc, could cause radioactive contamination, radiation burns, acute radiation syndrome or a combination of any of these above-mentioned disasters. Effects of radiation and the subsequent treatment depend on the severity of exposure and the organs directly involved. Radiation levels up to 200 rads lead to nausea and vomiting whilst radiation levels between 200 rads and 400 rads lead to diarrhea, vomiting and pneumonitis. Whilst 450 rads is lethal in 50 per cent population, doses above this cause increased fatality and organ involvement with the Central Nervous System being affected with 2000 rads radiation. Nuclear disaster management lies most importantly in identifying that patient who would recover if treated immediately. Whereas decontamination of skin and wounds is done first, immediate first aid may take priority in a seriously injured patient. In the event of internal contamination, effective decorporation maybe required. This is followed by prevention and treatment of infections in sterile conditions. Radiation burn injuries will require effective long-term management. Finally, what would be most important is the necessity to have suitable hospital care where bone marrow, stem cell transfusion and restitution of the immune system would take place.Defence Science Journal, 2011, 61(2, pp.113-117, DOI:http://dx.doi.org/10.14429/dsj.61.830

  7. [Solcoseryl--dental adherent paste in the treatment of acute radiation-induced inflammation of oral mucosa, gingivae and tongue].

    Science.gov (United States)

    Kryst, L; Kowalik, S; Bartkowski, S; Henning, G

    1990-07-01

    On the basis of a study carried out in three teaching departments of maxillofacial surgery the effect was analysed of Solcoseryl dental adherent paste and Linomag in the treatment of acute radiation-induced stomatitis. Both drugs were effective but Solcoseryl was superior to the other drug since it accelerated healing by about 50% and formed a protecting dressing on the inflamed mucosa.

  8. Acute toxicity profile of craniospinal irradiation with intensity-modulated radiation therapy in children with medulloblastoma: A prospective analysis

    NARCIS (Netherlands)

    Cox, M.C.; Kusters, J.M.; Gidding, C.E.M.; Schieving, J.H.; Lindert, E.J. van; Kaanders, J.H.A.M.; Janssens, G.O.R.J.

    2015-01-01

    BACKGROUND: To report on the acute toxicity in children with medulloblastoma undergoing intensity-modulated radiation therapy (IMRT) with daily intrafractionally modulated junctions. METHODS: Newly diagnosed patients, aged 3-21, with standard-risk (SR) or high-risk (HR) medulloblastoma were

  9. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Chlamydia Psittaci Vaccine (Feline... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall...

  10. Prediction and prevention of radiation induced lung toxicity

    OpenAIRE

    Wiegman, Erwin Mark

    2014-01-01

    De belangrijkste bijwerking van de radiotherapeutische behandeling van longkanker is stralingsgeïnduceerde longschade,oftewel Radiatie geInduceerde Long Toxiciteit (RILT). RILT ontstaat in twee fasen: een acute radiatie pneumonitis (6-12 weken na beëindiging van de radiotherapie) en longfibrose, die maanden na de behandeling kan ontstaat. Patiënten met radiatie pneumonitis hebben klachten van kortademigheid, hoesten en koorts. In ernstige gevallen kunnen zij zuurstof-afhankelijk worden en zel...

  11. Histopathological comparison of topical therapy modalities for acute radiation proctitis in an experimental rat model

    Institute of Scientific and Technical Information of China (English)

    Cagatay Korkut; Oktar Asoglu; Murat Aksoy; Yersu Kapran; Hatice Bilge; Nese Kiremit-Korkut; Mesut Parlak

    2006-01-01

    AIM: To evaluate the prevalent topical therapeutic modalities available for the treatment of acute radiation proctitis compared to formalin. METHODS: A total of 120 rats were used. Four groups (n = 30) were analyzed with one group for each of the following applied therapy modalities: control, mesalazine, formalin, betamethasone, and misoprostol. A single fraction of 17.5 Gy was delivered to each rat. The rats in control group rats were given saline, and the rats in the other three groups received appropriate enemas twice a day beginning on the first day after the irradiation until the day of euthanasia. On d 5, 10, and 15, ten rats from each group were euthanized and a pathologist who was unaware of treatment assignment examined the rectums using a scoring system. RESULTS: The histopathologic scores for surface epithelium, glands (crypts) and lamina propria stroma of the rectums reached their maximum level on d 10. The control and formalin groups had the highest and mesalazine had the lowest, respectively on d 10. On the 15th d, mesalazine, betamethasone, and misoprostol had the lowest scores of betamethasone. CONCLUSION: Mesalazine, betamethasone, and misoprostol are the best topical agents for radiation proctitis and formalin has an inflammatory effect and should not be used.

  12. Levofloxacin cures experimental pneumonic plague in African green monkeys.

    Directory of Open Access Journals (Sweden)

    Robert Colby Layton

    Full Text Available BACKGROUND: Yersinia pestis, the agent of plague, is considered a potential bioweapon due to rapid lethality when delivered as an aerosol. Levofloxacin was tested for primary pneumonic plague treatment in a nonhuman primate model mimicking human disease. METHODS AND RESULTS: Twenty-four African Green monkeys (AGMs, Chlorocebus aethiops were challenged via head-only aerosol inhalation with 3-145 (mean = 65 50% lethal (LD(50 doses of Y. pestis strain CO92. Telemetered body temperature >39 °C initiated intravenous infusions to seven 5% dextrose controls or 17 levofloxacin treated animals. Levofloxacin was administered as a "humanized" dose regimen of alternating 8 mg/kg and 2 mg/kg 30-min infusions every 24-h, continuing until animal death or 20 total infusions, followed by 14 days of observation. Fever appeared at 53-165 h and radiographs found multilobar pneumonia in all exposed animals. All control animals died of severe pneumonic plague within five days of aerosol exposure. All 16 animals infused with levofloxacin for 10 days survived. Levofloxacin treatment abolished bacteremia within 24 h in animals with confirmed pre-infusion bacteremia, and reduced tachypnea and leukocytosis but not fever during the first 2 days of infusions. CONCLUSION: Levofloxacin cures established pneumonic plague when treatment is initiated after the onset of fever in the lethal aerosol-challenged AGM nonhuman primate model, and can be considered for treatment of other forms of plague. Levofloxacin may also be considered for primary presumptive-use, multi-agent antibiotic in bioterrorism events prior to identification of the pathogen.

  13. Studies of adaptive response and mutation induction in MCF-10A cells following exposure to chronic or acute ionizing radiation.

    Science.gov (United States)

    Manesh, Sara Shakeri; Sangsuwan, Traimate; Wojcik, Andrzej; Haghdoost, Siamak

    2015-10-01

    A phenomenon in which exposure to a low adapting dose of radiation makes cells more resistant to the effects of a subsequent high dose exposure is termed radio-adaptive response. Adaptive response could hypothetically reduce the risk of late adverse effects of chronic or acute radiation exposures in humans. Understanding the underlying mechanisms of such responses is of relevance for radiation protection as well as for the clinical applications of radiation in medicine. However, due to the variability of responses depending on the model system and radiation condition, there is a need to further study under what conditions adaptive response can be induced. In this study, we analyzed if there is a dose rate dependence for the adapting dose, assuming that the adapting dose induces DNA response/repair pathways that are dose rate dependent. MCF-10A cells were exposed to a 50mGy adapting dose administered acutely (0.40Gy/min) or chronically (1.4mGy/h or 4.1mGy/h) and then irradiated by high acute challenging doses. The endpoints of study include clonogenic cell survival and mutation frequency at X-linked hprt locus. In another series of experiment, cells were exposed to 100mGy and 1Gy at different dose rates (acutely and chronically) and then the mutation frequencies were studied. Adaptive response was absent at the level of clonogenic survival. The mutation frequencies were significantly decreased in the cells pre-exposed to 50mGy at 1.4mGy/h followed by 1Gy acute exposure as challenging dose. Importantly, at single dose exposures (1 Gy or 100mGy), no differences at the level of mutation were found comparing different dose rates. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Hypersensitivity pneumonitis due to residential mosquito-coil smoke exposure

    Institute of Scientific and Technical Information of China (English)

    Gopall Roshnee; CAO Guo-qiang; CHEN Hong

    2011-01-01

    We reported a previously healthy 25-year-old female patient who developed hypersensitivity pneumonitis following repeated exposures to the smoke of mosquito coils. The patient presented with vague symptoms of cough and fever for 3 days. Diagnostic criteria proposed for clinical use in this case included history, exposure to a recognized antigen, physical examination, consistent radiographic images, bronchoalveolar lavage and lung biopsy. Much symptomatic relief and better radiographic response were noted after short-term use of oral corticosteroid and removal of the offending antigen.

  15. Whole acute toxicity removal from industrial and domestic effluents treated by electron beam radiation: emphasis on anionic surfactants

    Science.gov (United States)

    Moraes, M. C. F.; Romanelli, M. F.; Sena, H. C.; Pasqualini da Silva, G.; Sampa, M. H. O.; Borrely, S. I.

    2004-09-01

    Electron beam radiation has been applied to improve real industrial and domestic effluents received by Suzano wastewater treatment plant. Radiation efficacy has been evaluated as toxicity reduction, using two biological assays. Three sites were sampled and submitted for toxicity assays, anionic surfactant determination and electron beam irradiation. This paper shows the reduction of acute toxicity for both test-organisms, the marine bacteria Vibrio fischeri and the crustacean Daphnia similis. The raw toxic effluents exibitted from 0.6 ppm up to 11.67 ppm for anionic surfactant before being treated by the electron beam. Radiation processing resulted in reduction of the acute toxicity as well as surfactant removal. The final biological effluent was in general less toxic than other sites but the presence of anionic surfactants was evidenced.

  16. Transplantation of Endothelial Cells to Mitigate Acute and Chronic Radiation Injury to Vital Organs.

    Science.gov (United States)

    Rafii, Shahin; Ginsberg, Michael; Scandura, Joseph; Butler, Jason M; Ding, Bi-Sen

    2016-08-01

    Current therapeutic approaches for treatment of exposure to radiation involve the use of antioxidants, chelating agents, recombinant growth factors and transplantation of stem cells (e.g., hematopoietic stem cell transplantation). However, exposure to high-dose radiation is associated with severe damage to the vasculature of vital organs, often leading to impaired healing, tissue necrosis, thrombosis and defective regeneration caused by aberrant fibrosis. It is very unlikely that infusion of protective chemicals will reverse severe damage to the vascular endothelial cells (ECs). The role of irradiated vasculature in mediating acute and chronic radiation syndromes has not been fully appreciated or well studied. New approaches are necessary to replace and reconstitute ECs in organs that are irreversibly damaged by radiation. We have set forth the novel concept that ECs provide paracrine signals, also known as angiocrine signals, which not only promote healing of irradiated tissue but also direct organ regeneration without provoking fibrosis. We have developed innovative technologies that enable manufacturing and banking of human GMP-grade ECs. These ECs can be transplanted intravenously to home to and engraft to injured tissues where they augment organ repair, while preventing maladaptive fibrosis. In the past, therapeutic transplantation of ECs was not possible due to a shortage of availability of suitable donor cell sources and preclinical models, a lack of understanding of the immune privilege of ECs, and inadequate methodologies for expansion and banking of engraftable ECs. Recent advances made by our group as well as other laboratories have breached the most significant of these obstacles with the development of technologies to manufacture clinical-scale quantities of GMP-grade and human ECs in culture, including genetically diverse reprogrammed human amniotic cells into vascular ECs (rAC-VECs) or human pluripotent stem cells into vascular ECs (iVECs). This

  17. Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems

    Science.gov (United States)

    Dainiak, Nicholas; Gent, Robert Nicolas; Carr, Zhanat; Schneider, Rita; Bader, Judith; Buglova, Elena; Chao, Nelson; Coleman, C. Norman; Ganser, Arnold; Gorin, Claude; Hauer-Jensen, Martin; Huff, L. Andrew; Lillis-Hearne, Patricia; Maekawa, Kazuhiko; Nemhauser, Jeffrey; Powles, Ray; Schünemann, Holger; Shapiro, Alla; Stenke, Leif; Valverde, Nelson; Weinstock, David; White, Douglas; Albanese, Joseph; Meineke, Viktor

    2013-01-01

    Objectives The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature. Methods English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made. Results No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/ orshock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak

  18. CYTOMEGALOVIRUS INTERSTITIAL PNEUMONITIS FOLLOWING ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    XU Xiao-hua; HUANG Lian-sheng; ZHANG Xiao-hong; ZHU Kang-er; XU Yang; WU Dong; ZHAO Xiao-ying

    2005-01-01

    Objective: To explore the risk factors and prophylaxis and treatment of cytomegalovirus interstitial pneumonitis(CMV-IP) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: 43 patients who received allo-PBSCT were allocated to either a Gancyclovir(GCV)-prophylaxis group (n=19) or a non-GCV prophylaxis group (n=24).A comparison was made of the incidence of CMV-IP in patients given or not given prophylactic gancyclovir. Results: 9patients in non-GCV prophylaxis group developed late CMV-IP (P<0.05). Graft-versus-host-disease (GVHD) may be associated with a high risk of CMV-IP. 5 cases of CMV-IP were successfully treated with GCV, but 3 cases died of CMV-IP.The most common adverse event of GCV was neutropenia, but was reversible. Conclusion: CMV infection was a major cause of interstitial pneumonitis after allo-PBSCT, which correlated strongly with the severity of GVHD. Gancyclovir was shown to be effective in both prophylaxis and treatment of CMV-IP.

  19. Delayed Paclitaxel-Trastuzumab-Induced Interstitial Pneumonitis in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Omalkhair Abulkhair

    2011-04-01

    Full Text Available Pneumonitis is a rare but serious complication associated with paclitaxel and/or trastuzumab treatment. We report a 51-year-old female patient with locally advanced breast cancer who presented with shortness of breath, fever, dry cough and pulmonary infiltrates. She had been treated without complications for 10 weeks with paclitaxel (Taxol® and trastuzumab (Herceptin® as neoadjuvant therapy, with complete clinical and pathological response. Infections and cardiomyopathy were excluded as causes of her symptoms. Bronchoscopy and biopsy were performed and a diagnosis of drug-induced interstitial pneumonitis was made. After treatment with steroids, the patient showed a significant response in less than 24 h; she was discharged home without the need for oxygen less than 48 h after therapy initiation. Although no causative association could be found between either trastuzumab or paclitaxel and this patient’s pulmonary syndrome, the potential for such toxicity should be considered, especially as paclitaxel/trastuzumab is a vey common combination therapy for breast cancer.

  20. Do variations in mast cell hyperplasia account for differences in radiation-induced lung injury among different mouse strains, rats and nonhuman primates?

    Science.gov (United States)

    Down, Julian D; Medhora, Meetha; Jackson, Isabel L; Cline, J Mark; Vujaskovic, Zeljko

    2013-08-01

    The role of mast cell infiltrates in the pathology of radiation damage to the lung has been a subject of continuing investigation over the past four decades. This has been accompanied by a number of proposals as to how mast cells and the secretory products thereof participate in the generation of acute inflammation (pneumonitis) and the chronic process of collagen deposition (fibrosis). An additional pathophysiology examines the possible connection between mast cell hyperplasia and pulmonary hypertension through the release of vasoactive mediators. The timing and magnitude of pneumonitis and fibrosis are known to vary tremendously among different genetic mouse strains and animal species. Therefore, we have systematically compared mast cell numbers in lung sections from nine mouse strains, two rat strains and nonhuman primates (NHP) after whole thorax irradiation (WTI) at doses ranging from 10-15 Gy and at the time of entering respiratory distress. Mice of the BALB/c strain had a dramatic increase in interstitial mast cell numbers, similar to WAG/Rij and August rats, while relatively low levels of mast cell infiltrate were observed in other mouse strains (CBA, C3H, B6, C57L, WHT and TO mice). Enumeration of mast cell number in five NHPs (rhesus macaque), exhibiting severe pneumonitis at 17 weeks after 10 Gy WTI, also indicated a low response shared by the majority of mouse strains. There appeared to be no relationship between the mast cell response and the strain-dependent susceptibility towards pneumonitis or fibrosis. Further investigations are required to explore the possible participation of mast cells in mediating specific vascular responses and whether a genetically diverse mast cell response occurs in humans.

  1. Acute clinical adverse radiation effects after Gamma Knife surgery for vestibular schwannomas.

    Science.gov (United States)

    Tuleasca, Constantin; George, Mercy; Faouzi, Mohamed; Schiappacasse, Luis; Leroy, Henri-Arthur; Zeverino, Michele; Daniel, Roy Thomas; Maire, Raphael; Levivier, Marc

    2016-12-01

    OBJECTIVE Vestibular schwannomas (VSs) represent a common indication of Gamma Knife surgery (GKS). While most studies focus on the long-term morbidity and adverse radiation effects (AREs), none describe the acute clinical AREs that might appear on a short-term basis. These types of events are investigated, and their incidence, type, and outcomes are reported in the present paper. METHODS The included patients were treated between July 2010 and March 2016, underwent at least 6 months of follow-up, and presented with a disabling symptom during the first 6 months after GKS that affected their quality of life. The timing of appearance, as well as the type of main symptom and outcome, were noted. The prescribed dose was 12 Gy at the margin. RESULTS Thirty-five (22%) of 159 patients who fulfilled the inclusion criteria had acute clinical AREs. The mean followup period was 30 months (range 6-49.2 months). The mean time of appearance was 37.9 days (median 31 days; range 3-110 days). In patients with de novo symptoms, the more frequent symptoms were vertigo (n = 4; 11.4%) and gait disturbance (n = 3; 8.6%). The exacerbation of a preexisting symptom was more frequently related to hearing loss (n = 10; 28.6%), followed by gait disturbance (n = 7; 20%) and vertigo (n = 3, 8.6%). In the univariate logistic regression analysis, the following factors were statistically significant: age (p = 0.002; odds ratio [OR] 0.96), hearing at baseline by Gardner-Robertson (GR) class (p = 0.006; OR 0.21), pure tone average at baseline (p = 0.006; OR 0.97), and Koos grade at baseline (with Koos Grade I used as a reference) (for Koos Grade II, OR 0.17 and p = 0.002; for Koos Grade III, OR 0.42 and p = 0.05). The following were not statistically significant but showed a tendency toward significance: the number of isocenters (p = 0.06; OR 0.94) and the maximal dose received by the cochlea (p = 0.07; OR 0.74). Fractional polynomial regression analysis showed a nonlinear relationship between the

  2. Derivation of hazardous doses for amphibians acutely exposed to ionising radiation.

    Science.gov (United States)

    Fuma, Shoichi; Watanabe, Yoshito; Kawaguchi, Isao; Takata, Toshitaro; Kubota, Yoshihisa; Ban-Nai, Tadaaki; Yoshida, Satoshi

    2012-01-01

    Derivation of effect benchmark values for each taxonomic group, which has been difficult due to lack of experimental effects data, is required for more adequate protection of the environment from ionising radiation. Estimation of effects doses from nuclear DNA mass and subsequent species sensitivity distribution (SSD) analysis were proposed as a method for such a derivation in acute irradiation situations for assumed nuclear accident scenarios. As a case study, 5% hazardous doses (HD₅s), at which only 5% of species are acutely affected at 50% or higher lethality, were estimated on a global scale. After nuclear DNA mass data were obtained from a database, 50% lethal doses (LD₅₀s) for 4.8 and 36% of the global Anura and Caudata species, respectively, were estimated by correlative equations between nuclear DNA mass and LD₅₀s. Differences between estimated and experimental LD₅₀s were within a factor of three. The HD₅s obtained by the SSD analysis of these estimated LD₅₀s data were 5.0 and 3.1 Gy for Anura and Caudata, respectively. This approach was also applied to the derivation of regional HD₅s. The respective HD₅s were 6.5 and 3.2 Gy for Anura and Caudata inhabiting Japan. This HD₅ value for the Japanese Anura was significantly higher than the global value, while Caudata had no significant difference in global and Japanese HD₅s. These results suggest that this approach is also useful for derivation of regional benchmark values, some of which are likely different from the global values.

  3. Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, Francois, E-mail: francois.meyer@chuq.qc.ca [Laval University Cancer Research Center, Centre hospitalier universitaire de Quebec - L' Hotel-Dieu de Quebec, Quebec (Canada); Fortin, Andre; Wang, Chang Shu [Radiation Therapy Department, Centre hospitalier universitaire de Quebec - L' Hotel-Dieu de Quebec, Quebec (Canada); Liu, Geoffrey [Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto (Canada); Bairati, Isabelle [Laval University Cancer Research Center, Centre hospitalier universitaire de Quebec - L' Hotel-Dieu de Quebec, Quebec (Canada)

    2012-03-15

    Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting could help

  4. Establishing a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome

    Science.gov (United States)

    Plett, P. Artur; Sampson, Carol H.; Chua, Hui Lin; Joshi, Mandar; Booth, Catherine; Gough, Alec; Johnson, Cynthia S.; Katz, Barry P.; Farese, Ann M.; Parker, Jeffrey; MacVittie, Thomas J.; Orschell, Christie M.

    2012-01-01

    We have developed a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS) for efficacy testing of medical countermeasures (MCM) against radiation according to the FDA Animal Rule. Ten to 12 week old male and female C57BL/6 mice were exposed to the LD50/30-LD70/30 dose of total body irradiation (TBI, 137Cs, 0.62-0.67 Gy min-1) in the morning hours when mice were determined to be most radiosensitive, and assessed for 30 day survival and mean survival time (MST). Antibiotics were delivered in the drinking water on days 4-30 post-TBI at a concentration based on the amount of water that lethally-irradiated mice were found to consume. The fluoroquinolones, ciprofloxacin and levofloxacin, and the tetracycline doxycycline and aminoglycoside neomycin, all significantly increased MST of decedent mice, while ciprofloxacin (p=0.061) and doxycycline + neomycin (p=0.005) showed at least some efficacy to increase 30 day survival. Blood sampling (30uL/mouse every 5th day) was found to negatively impact 30 day survival. Histopathology of tissues harvested from non-moribund mice showed expected effects of lethal irradiation, while moribund mice were largely septicemic with a preponderance of enteric organisms. Kinetics of loss and recovery of peripheral blood cells in untreated mice and those treated with two MCM, granulocyte-colony stimulating factor and Amifostine, further characterized and validated our model for use in screening studies and pivotal efficacy studies of candidate MCM for licensure to treat irradiated individuals suffering from H-ARS. PMID:22929467

  5. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kwint, Margriet [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Uyterlinde, Wilma [Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Heuvel, Michel van den [Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Knegjens, Joost; Herk, Marcel van [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Belderbos, Jose, E-mail: j.belderbos@nki.nl [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2012-10-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

  6. Preliminary clinical findings on NEUMUNE as a potential treatment for acute radiation syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Stickney, Dwight R; Groothuis, Jessie R; Ahlem, Clarence; Kennedy, Mike; Miller, Barry S; Onizuka-Handa, Nanette; Schlangen, Karen M; Destiche, Daniel; Reading, Chris; Garsd, Armando; Frincke, James M [Harbor Biosciences, 9171 Towne Centre Drive, Suite 180, San Diego, CA 92122 (United States)

    2010-12-01

    5-androstenediol (5-AED) has been advanced as a possible countermeasure for treating the haematological component of acute radiation syndrome (ARS). It has been used in animal models to stimulate both innate and adaptive immunity and treat infection and radiation-induced immune suppression. We here report on the safety, tolerability and haematologic activity of 5-AED in four double-blinded, randomized, placebo-controlled studies on healthy adults including elderly subjects. A 5-AED injectable suspension formulation (NEUMUNE) or placebo was administered intramuscularly as either a single injection, or once daily for five consecutive days at doses of 50, 100, 200 or 400 mg. Subjects (n = 129) were randomized to receive NEUMUNE (n = 95) or the placebo (n = 34). NEUMUNE was generally well-tolerated; the most frequent adverse events were local injection site reactions (n = 104, 81%) that were transient, dose-volume dependent, mild to moderate in severity, and that resolved over the course of the study. Blood chemistries revealed a transient increase (up to 28%) in creatine phosphokinase and C-reactive protein levels consistent with intramuscular injection and injection site irritation. The blood concentration profile of 5-AED is consistent with a depot formulation that increases in disproportionate increments following each dose. NEUMUNE significantly increased circulating neutrophils (p < 0.001) and platelets (p < 0.001) in the peripheral blood of adult and elderly subjects. A dose-response relationship was identified. Findings suggest that parenteral administration of 5-AED in aqueous suspension may be a safe and effective means to stimulate innate immunity and alleviate neutropenia and thrombocytopenia associated with ARS.

  7. Health effects in those with acute radiation sickness from the Chernobyl accident.

    Science.gov (United States)

    Mettler, Fred A; Gus'kova, Angelina K; Gusev, Igor

    2007-11-01

    The Chernobyl accident resulted in almost one-third of the reported cases of acute radiation sickness (ARS) reported worldwide. Cases occurred among the plant employees and first responders but not among the evacuated populations or general population. The diagnosis of ARS was initially considered for 237 persons based on symptoms of nausea, vomiting, and diarrhea. Ultimately, the diagnosis of ARS was confirmed in 134 persons. There were 28 short term deaths of which 95% occurred at whole body doses in excess of 6.5 Gy. Underlying bone marrow failure was the main contributor to all deaths during the first 2 mo. Allogenic bone marrow transplantation was performed on 13 patients and an additional six received human fetal liver cells. All of these patients died except one individual who later was discovered to have recovered his own marrow and rejected the transplant. Two or three patients were felt to have died as a result of transplant complications. Skin doses exceeded bone marrow doses by a factor of 10-30, and at least 19 of the deaths were felt to be primarily due to infection from large area beta burns. Internal contamination was of relatively minor importance in treatment. By the end of 2001, an additional 14 ARS survivors died from various causes. Long term treatment has included therapy for beta burn fibrosis and skin atrophy as well as for cataracts.

  8. Mesenchymal stem cell therapy for acute radiation syndrome:Innovative medical approaches in military medicine

    Institute of Scientific and Technical Information of China (English)

    Erik B.Eaton Jr.; Timothy R.Varney

    2014-01-01

    After a radiological or nuclear event, acute radiation syndrome (ARS) will present complex medical challenges that could involve the treatment of hundreds to thousands of patients. Current medical doctrine is based on limited clinical data and remains inadequate. Efforts to develop medical innovations that address ARS complications are unlikely to be generated by the industry because of market uncertainties specific to this type of injury. A prospective strategy could be the integration of cellular therapy to meet the medical demands of ARS. The most clinically advanced cellular therapy to date is the administration of mesenchymal stem cells (MSCs). Results of currently published investigations describing MSC safety and efficacy in a variety of injury and disease models demonstrate the unique qualities of this reparative cell population in adapting to the specific requirements of the damaged tissue in which the cells integrate. This report puts forward a rationale for the further evaluation of MSC therapy to address the current unmet medical needs of ARS. We propose that the exploration of this novel therapy for the treatment of the multivariate complications of ARS could be of invaluable benefit to military medicine.

  9. Cranial Radiation for Pediatric T-Lineage Acute Lymphoblastic Leukemia: A Systematic Review and Meta-analysis

    OpenAIRE

    Kelly, Michael J.; Thomas A. Trikalinos; Dahabreh, Issa J.; Gianferante, Matthew; Parsons, Susan K.

    2014-01-01

    There are heterogeneous approaches to cranial irradiation therapy (CRT) for T-lineage acute lymphoblastic leukemia (T-ALL). We performed a systematic review of studies that specified a radiation strategy and reported survival for pediatric T-ALL. Our analysis included 62 publications reporting 78 treatment groups (patient n=5844). The average event-free survival (EFS) was higher by 6% per 5 years (p

  10. Hypersensitivity pneumonitis: beyond classic occupational disease-changing concepts of diagnosis and management.

    Science.gov (United States)

    Jacobs, Robert L; Andrews, Charles P; Coalson, Jacqueline J

    2005-08-01

    To review inhaled antigens in home environments that cause hypersensitivity pneumonitis (HP) of varied clinical expressions and histopathologic patterns. Computer-assisted MEDLINE and manual searches for articles concerning HP, interstitial lung disease (ILD), epidemiology of HP and ILD, challenge procedures of HP, and indoor fungi. Published articles concerning inhaled antigens in home environments and HP were selected. Current criteria for the diagnosis of HP are too restrictive, because most apply only to the classic acute presentation and are of limited value in the subacute and insidious forms. Clinical expressions vary across the gamut of respiratory tract signs and symptoms. Patterns on lung biopsy may include all histopathologic descriptions of idiopathic ILD. The home is the likely causative environment rather than the workplace. Exposures may be occult and require in-depth environmental histories and on-site investigations to detect antigens and sources. Natural or environmental challenges have become an important tool for diagnosing HP and determining effectiveness of remediation. Early diagnosis and effective remediation of the cause lead to a high survival rate, whereas diagnosis in advanced stages leads to disability and/or premature death.

  11. Helminth infections predispose mice to pneumococcal pneumonia but not to other pneumonic pathogens.

    Science.gov (United States)

    Apiwattanakul, Nopporn; Thomas, Paul G; Kuhn, Raymond E; Herbert, De'Broski R; McCullers, Jonathan A

    2014-10-01

    Pneumonia is the leading killer of children worldwide. Here, we report that helminth-infected mice develop fatal pneumonia when challenged with Streptococcus pneumoniae. Mice were chronically infected with either the flatworm Taenia crassiceps or the roundworm Heligmosomoides polygyrus. Upon challenge with a pneumonic type 3 strain of S. pneumoniae (A66.1), the worm-infected mice developed pneumonia at a rate and to a degree higher than age-matched control mice as measured by bioluminescent imaging and lung titers. This predisposition to pneumonia appears to be specific to S. pneumoniae, as worm-infected mice did not show evidence of increased morbidity when challenged with a lethal dose of influenza virus or sublethal doses of Staphylococcus aureus or Listeria monocytogenes. The defect was also present when worm-infected mice were challenged with a type 2 sepsis-causing strain (D39); an increased rate of pneumonia, decreased survival, and increased lung and blood titers were found. Pneumococcal colonization and immunity against acute otitis media were unaffected. Anti-helminthic treatment in the H. polygyrus model reversed this susceptibility. We conclude that helminth coinfection predisposes mice to fatal pneumococcal pneumonia by promoting increased outgrowth of bacteria in the lungs and blood. These data have broad implications for the prevention and treatment for pneumonia in the developing world, where helminth infections are endemic and pneumococcal pneumonia is common.

  12. Combined pulmonary fibrosis and emphysema in hypersensitivity pneumonitis.

    Science.gov (United States)

    Soumagne, Thibaud; Pana-Katatali, Héloïse; Degano, Bruno; Dalphin, Jean-Charles

    2015-12-21

    Combined pulmonary fibrosis and emphysema is a distinct syndrome reported in patients who smoke. A 72-year-old, never-smoking female dairy farmer was referred for progressive dyspnoea on exertion, basal crackles on auscultation, normal spirometry and normal lung volumes but decreased diffusing capacity of the lung for carbon monoxide, centrilobular emphysema in the upper zones of the lungs and diffuse infiltrative lung disease in the lower zones on high-resolution CT scan. Bronchoalveolar lavage differential cell count showed 35% lymphocytosis, and precipitating antibodies for Wallemia sebi, Trichoderma species and Cladosporium sphaerospermum were identified. The diagnosis of farmer's lung disease with combined pulmonary fibrosis and emphysema was retained. This case highlights for the first time that hypersensitivity pneumonitis should be suspected in the setting of combined pulmonary fibrosis and emphysema in non-smoking patients.

  13. Childhood hypersensitivity pneumonitis associated with fungal contamination of indoor hydroponics.

    Science.gov (United States)

    Engelhart, Steffen; Rietschel, Ernst; Exner, Martin; Lange, Lars

    2009-01-01

    Childhood hypersensitivity pneumonitis (HP) is often associated with exposure to antigens in the home environment. We describe a case of HP associated with indoor hydroponics in a 14-year-old girl. Water samples from hydroponics revealed Aureobasidium pullulans as the dominant fungal micro-organism (10(4)CFU/ml). The diagnosis is supported by the existence of serum precipitating antibodies against A. pullulans, lymphocytic alveolitis on bronchoalveolar lavage (BAL) fluid, a corresponding reaction on a lung biopsy, and the sustained absence of clinical symptoms following the removal of hydroponics from the home. We conclude that hydroponics should be considered as potential sources of fungal contaminants when checking for indoor health complaints.

  14. Prognostic effects of preoperative obstructive pneumonitis or atelectasis and comparison with tumor size in non-small cell lung cancer.

    Science.gov (United States)

    Pang, Zhaofei; Ding, Nan; Dong, Wei; Ni, Yang; Zhang, Tiehong; Qu, Xiao; Du, Jiajun; Liu, Qi

    2017-03-01

    In the eighth TNM staging system proposal, lung cancer with part or complete obstructive pneumonitis/atelectasis was classified to T2 category, and dividing lines of T category were changed. We conducted this study to search prognostic effect of preoperative obstructive pneumonitis/atelectasis and its comparison with tumor size. We collected clinical characteristics, preoperative hematological indicators, follow-up information of 1,313 lung cancer patients. Chi-square test was used to search relationship between obstruction pneumonitis/atelectasis and other factors. Kaplan-Meier (K-M) curves and cox regression methods were used for survival analysis. Preoperative obstructive pneumonitis/atelectasis indicated shorter OS (HR: 1.308; 95% CI: 1.058-1.619) and RFS (HR: 1.276; 95% CI: 1.032-1.579) as an independent factor. In comparison with tumor size, we found patients with obstructive pneumonitis/atelectasis and T1 size tumor had similar prognosis to those with T2 size but without obstructive pneumonitis/atelectasis, and OS, RFS of patients with obstructive pneumonitis/atelectasis and T2 size were significantly shorter than those with T2 tumor size but without obstructive pneumonitis/atelectasis, while similar to patients with T3 tumor size but without obstructive pneumonitis/atelectasis according to division by the eighth edition. We also found obstructive pneumonitis/atelectasis was significantly related to higher neutrophil (Psize in the eighth TNM staging system.

  15. Interstitial pneumonitis is a frequent complication in liver transplant recipients treated with sirolimus.

    LENUS (Irish Health Repository)

    Morcos, A

    2012-06-01

    Sirolimus is a powerful immunosuppressive drug which is being used increasingly after liver transplantation because of its renal sparing and anti-tumour effects. It has been associated with uncommon, but potentially fatal, interstitial pneumonitis.

  16. Migratory eosinophilic alveolitis caused by radiation therapy.

    Science.gov (United States)

    Lim, Jun Hyeok; Nam, Hae-Seong; Kim, Hun Jung; Choi, Chang-Hwan; Park, In-Suh; Cho, Jae Hwa; Ryu, Jeong-Seon; Kwak, Seung Min; Lee, Hong Lyeol

    2015-05-01

    Although radiation pneumonitis is usually confined to irradiated areas, some studies have reported that radiation-induced lymphocytic alveolitis can also spread to the non-irradiated lung. However, there have been few reports of radiation-induced eosinophilic alveolitis. We report the case of a 27-year-old female with radiation pneumonitis, occurring 4 months after radiation therapy for cancer of the left breast. Clinical and radiological relapse followed withdrawal of corticosteroids. Examination of bronchoalveolar lavage (BAL) in patchy airspace consolidations revealed increased eosinophil counts. Finally, clinical and radiological signs resolved rapidly after reintroduction of corticosteroids. Eosinophilic alveolitis may be promoted by radiation therapy. In the present case report, possible mechanisms for radiation-induced eosinophilic alveolitis are also reviewed.

  17. Acute and late toxicity in prostate cancer patients treated by dose escalated intensity modulated radiation therapy and organ tracking

    Directory of Open Access Journals (Sweden)

    Behrensmeier Frank

    2008-10-01

    Full Text Available Abstract Background To report acute and late toxicity in prostate cancer patients treated by dose escalated intensity-modulated radiation therapy (IMRT and organ tracking. Methods From 06/2004 to 12/2005 39 men were treated by 80 Gy IMRT along with organ tracking. Median age was 69 years, risk of recurrence was low 18%, intermediate 21% and high in 61% patients. Hormone therapy (HT was received by 74% of patients. Toxicity was scored according to the CTC scale version 3.0. Median follow-up (FU was 29 months. Results Acute and maximal late grade 2 gastrointestinal (GI toxicity was 3% and 8%, late grade 2 GI toxicity dropped to 0% at the end of FU. No acute or late grade 3 GI toxicity was observed. Grade 2 and 3 pre-treatment genitourinary (GU morbidity (PGUM was 20% and 5%. Acute and maximal late grade 2 GU toxicity was 56% and 28% and late grade 2 GU toxicity decreased to 15% of patients at the end of FU. Acute and maximal late grade 3 GU toxicity was 8% and 3%, respectively. Decreased late ≥ grade 2 GU toxicity free survival was associated with higher age (P = .025, absence of HT (P = .016 and higher PGUM (P Discussion GI toxicity rates after IMRT and organ tracking are excellent, GU toxicity rates are strongly related to PGUM.

  18. Everolimus-induced Pneumonitis after Drug-eluting Stent Implantation: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, Susumu, E-mail: susumu1029@gmail.com; Kikuchi, Naoshi; Ichikawa, Atsuo; Sano, Go; Satoh, Keita; Sugino, Keishi; Isobe, Kazutoshi; Takai, Yujiro [Toho University School of Medicine, Department of Respiratory Medicine (Japan); Shibuya, Kazutoshi [Toho University School of Medicine, Department of Pathology (Japan); Homma, Sakae [Toho University School of Medicine, Department of Respiratory Medicine (Japan)

    2013-08-01

    Despite the wide use of everolimus as an antineoplastic coating agent for coronary stents to reduce the rate of restenosis, little is known about the health hazards of everolimus-eluting stents (EES). We describe a case of pneumonitis that developed 2 months after EES implantation for angina. Lung pathology demonstrated an organizing pneumonia pattern that responded to corticosteroid therapy. Although the efficacy of EES for ischemic heart disease is well established, EES carries a risk of pneumonitis.

  19. 内生场热疗联合糖皮质激素治疗急性放射性肺炎的疗效观察%Efficacy of local endogenefic thermotherapy combined with glucocorticoid for acute radiation pneumonia

    Institute of Scientific and Technical Information of China (English)

    黄建国; 卢宁; 王勇强; 赵晓伟

    2013-01-01

    目的:观察内生场热疗联合糖皮质激素治疗放射性肺炎的临床疗效.方法:86例放射性肺炎患者随机分为4组,分别给予对应治疗后,根据治疗后的症状、体征和影像学检查结果判定疗效.结果:内生场热疗和地塞米松联合治疗组患者,咳嗽、咳痰、胸闷气促症状以及呼吸困难症状有明显改善或消失,胸部CT提示肺部炎症消失或减轻,显效10例,有效10例,有效率90.9%,与治疗前相比均具有显著统计学差异(P<0.01).糖皮质激素组及热疗组患者经治疗后症状均有一定改善,其中糖皮质激素组显效5例,有效10例,有效率68.2%;热疗组显效6例,有效8例,有效率63.6%.对照组患者显效1例,有效3例,有效率25%.3个治疗组有效率均显著高于对照组(P<0.01),联合治疗组有效率显著高于糖皮质激素组(P<0.05)及热疗组(P<0.05).结论:内生场热疗联合糖皮质激素治疗放射性肺炎,疗效显著,值得临床推广应用.%Objective: To observe the clinical efficacy of local endogenefic thermotherapy combined with glucocor-ticoids for acute radiation pneumonia. Methods: All 86 cases of radiation pneumonitis were randomly divided into four groups and given the corresponding treatment. After treatment, the efficacy was determined according the symptoms, signs and imaging findings. Results: The patients treated with local endogenefic thermotherapy combined with glucocorticoids,symptoms including cough,sputum,chest tightness,shortness of breath and dyspnea were significantly improved or disappeared and lung inflammation was disappeared or reduced shown by chest CT. The excellent effective and effective cases both were 10 respectively and the effective rate was 90.9% (P<0.01,compared with before treatment). Patients'symptoms treated with glucocorticoid and hyperthermia have improved to some extent. The excellent effective and effective cases were 5 and 10 respectively and the effective rate was 68. 2

  20. Clarithromycin-induced acute interstitial nephritis and minimal change disease

    OpenAIRE

    Russell, Wendy; Smith, William

    2009-01-01

    Drug associated acute interstitial nephritis and minimal change disease has been well documented but the simultaneous presentation of both is rare and has not been reported with clarithromycin. We describe a case of simultaneous acute tubulointerstitial nephritis and minimal change disease induced by clarithromycin. The patient had acute kidney injury, nephrotic syndrome, eosinophilic pneumonitis and a maculopapular skin rash. The role of steroid therapy in acute interstitial nephritis is con...

  1. BiodosEPR-2006 Meeting: Acute dosimetry consensus committee recommendations on biodosimetry applications in events involving uses of radiation by terrorists and radiation accidents

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, George A. [U.S. Department of Health and Human Services, Office of Preparedness and Emergency Operations, 200 Independence Avenue, SW, Room 403B-1, Washington, DC 20201 (United States); Swartz, Harold M. [Dept. of Radiology and Physiology Dept., Dartmouth Medical School, HB 7785, Vail 702, Rubin 601, Hanover, NH 03755 (United States); Amundson, Sally A. [Center for Radiological Research, Columbia University Medical Center, 630 W. 168th Street, VC11-215, New York, NY 10032 (United States); Blakely, William F. [Armed Forces Radiobiology Research Inst., 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: blakely@afrri.usuhs.mil; Buddemeier, Brooke [Science and Technology, U.S. Department of Homeland Security, Washington, DC 20528 (United States); Gallez, Bernard [Biomedical Magnetic Resonance Unit and Lab. of Medicinal Chemistry and Radiopharmacy, Univ. Catholique de Louvain, Brussels (Belgium); Dainiak, Nicholas [Dept. of Medicine, Bridgeport Hospital, 267 Grant Street, Bridgeport, CT 06610 (United States); Goans, Ronald E. [MJW Corporation, 1422 Eagle Bend Drive, Clinton, TN 37716-4029 (United States); Hayes, Robert B. [Remote Sensing Lab., MS RSL-47, P.O. Box 98421, Las Vegas, NV 89193 (United States); Lowry, Patrick C. [Radiation Emergency Assistance Center/Training Site (REAC/TS), Oak Ridge Associated Universities, P.O. Box 117, Oak Ridge, TN 37831-0117 (United States); Noska, Michael A. [Food and Drug Administration, FDA/CDRH, 1350 Piccard Drive, HFZ-240, Rockville, MD 20850 (United States); Okunieff, Paul [Dept. of Radiation Oncology (Box 647), Univ. of Rochester, 601 Elmwood Avenue, Rochester, NY 14642 (United States); Salner, Andrew L. [Helen and Harry Gray Cancer Center, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102 (United States); Schauer, David A. [National Council on Radiation Protection and Measurements, 7910 Woodmont Avenue, Suite 400, Bethesda, MD 20814-3095 (United States)] (and others)

    2007-07-15

    In the aftermath of a radiological terrorism incident or mass-casualty radiation accident, first responders and receivers require prior guidance and pre-positioned resources for assessment, triage and medical management of affected individuals [NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA]. Several recent articles [Dainiak, N., Waselenko, J.K., Armitage, J.O., MacVittie, T.J., Farese, A.M., 2003. The hematologist and radiation casualties. Hematology (Am. Soc. Hematol. Educ. Program) 473-496; Waselenko, J.K., MacVittie, T.J., Blakely, W.F., Pesik, N., Wiley, A.L., Dickerson, W.E., Tsu, H., Confer, D.L., Coleman, C.N., Seed, T., Lowry, P., Armitage, J.O., Dainiak, N., Strategic National Stockpile Radiation Working Group, 2004. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann. Intern. Med. 140(12), 1037-1051; Blakely, W.F., Salter, C.A., Prasanna, P.G., 2005. Early-response biological dosimetry-recommended countermeasure enhancements for mass-casualty radiological incidents and terrorism. Health Phys. 89(5), 494-504; Goans, R.E., Waselenko, J.K., 2005. Medical management of radiation casualties. Health Phys. 89(5), 505-512; Swartz, H.M., Iwasaki, A., Walczak, T., Demidenko, E., Salikhov, I., Lesniewski, P., Starewicz, P., Schauer, D., Romanyukha, A., 2005. Measurements of clinically significant doses of ionizing radiation using non-invasive in vivo EPR spectroscopy of teeth in situ. Appl. Radiat. Isot. 62, 293-299; . Acute radiation injury: contingency planning for triage, supportive care, and transplantation. Biol. Blood Marrow Transplant. 12(6), 672-682], national [. Management of persons accidentally contaminated with radionuclides. NCRP Report No. 65, Bethesda, Maryland, USA; . Management of terrorist events involving radioactive material. NCRP Report No. 138, Bethesda, Maryland

  2. Radiation-Induced Differentiation in Human Lung Fibroblast

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sa-Rah; Ahn, Ji-Yeon; Han, Young-Soo; Shim, Jie-Young; Yun, Yeon-Sook; Song, Jie-Young [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2007-10-15

    One of the most common tumors in many countries is lung cancer and patients with lung cancer may take radiotherapy. Although radiotherapy may have its own advantages, it can also induce serious problems such as acute radiation pneumonitis and pulmonary fibrosis. Pulmonary fibrosis is characterized by excessive production of {alpha}-SMA and accumulation of extracellular matrix (ECM) such as collagen and fibronectin. There has been a great amount of research about fibrosis but the exact mechanism causing the reaction is not elucidated especially in radiation-induced fibrosis. Until now it has been known that several factors such as transforming growth factor (TGF-{beta}), tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) are related to fibrosis. Among them TGF-{beta} with Smad signaling is known to be the main stream and other signaling molecules such as MAPK, ERK and JNK (3) also participates in the process. In addition to those above factors, it is thought that more diverse and complicate mechanisms may involve in the radiationinduced fibrosis. Therefore, to investigate the underlying mechanisms in radiation induced fibrosis, first of all, we confirmed whether radiation induces trans differentiation in human normal lung fibroblasts. Here, we suggest that not only TGF-{beta} but also radiation can induce trans differentiation in human lung fibroblast WI-38 and IMR-90.

  3. Rabbit model of radiation-induced lung injury

    Institute of Scientific and Technical Information of China (English)

    Zhen-Zong Du; Hua Ren; Jian-Fei Song; Li-Fei Zhang; Feng Lin; Hai-Yong Wang

    2013-01-01

    Objective:To explore the feasibility of establishing an animal model of chronic radiation-induced lung injury.Methods:Twenty-eightNewZealand white rabbits were randomly divided into3 groups(the right lung irradiation group, the whole lung irradiation group and the control group).Animal model of radiation-induced lung injury was established by high-does radiotherapy in the irradiation groups, then all rabbits underwentCT and pathological examinations at1,2,4,8,12,16 weeks, respectively after radiation.Results:Within4 weeks of irradiation, some rabbits in the right lung irradiation group and whole lung irradiation group died. CT and pathological examinations all showed acute radiation pneumonitis.At8-12 weeks after irradiation,CT scanning showed ground glass samples signs, patchy shadows and fibrotic stripes. Pathological examination showed the fibrosis pulmonary alveolar wall thickened obviously. Conclusions:The clinical animal model of chronic radiation-induced lung injury which corresponds to practical conditions in clinic can be successfully established.

  4. Radiation carcinogenesis and acute radiation mortality in the rat as produced by 2.2 GeV protons

    Science.gov (United States)

    Shellabarger, C. J.; Straub, R. F.; Jesseph, J. E.; Montour, J. L.

    1972-01-01

    Biological studies, proton carcinogenesis, the interaction of protons and gamma-rays on carcinogenesis, proton-induced acute mortality, and chemical protection against proton-induced acute mortality were studied in the rat and these proton-produced responses were compared to similar responses produced by gamma-rays or X-rays. Litter-mate mice were assigned to each experimental and control group so that approximately equal numbers of litter mates were placed in each group. Animals to be studied for mammary neoplasia were handled for 365 days post-exposure when all animals alive were killed. All animals were examined frequently for mammary tumors and as these were found, they were removed, sectioned and given a pathologic classification.

  5. Radiation-Induced Esophagitis is Mitigated by Soy Isoflavones

    Directory of Open Access Journals (Sweden)

    Matthew D Fountain

    2016-11-01

    Full Text Available Introduction: Lung cancer patients receiving radiotherapy present with acute esophagitis and chronic fibrosis, as a result of radiation injury to esophageal tissues. We have shown that soy isoflavones alleviate pneumonitis and fibrosis caused by radiation toxicity to normal lung. The effect of soy isoflavones on esophagitis histopathological changes induced by radiation was investigated. Methods: C57BL/6 mice were treated with 10 Gy or 25 Gy single thoracic irradiation and soy isoflavones for up to 16 weeks. Damage to esophageal tissues was assessed by H&E, Masson’s Trichrome and Ki-67 staining at 1, 4, 10, 16 weeks after radiation. The effects on smooth muscle cells and leukocyte infiltration were determined by immunohistochemistry using anti-αSMA and anti-CD45 respectively. Results: Radiation caused thickening of esophageal tissue layers that was significantly reduced by soy isoflavones. Major radiation alterations included hypertrophy of basal cells in mucosal epithelium and damage to smooth muscle cells in muscularis mucosae as well as disruption of collagen fibers in lamina propria connective tissue with leukocyte infiltration. These effects were observed as early as one week after radiation and were more pronounced with a higher dose of 25 Gy. Soy isoflavones limited the extent of tissue damage induced by radiation both at 10 and 25 Gy.Conclusions: Soy isoflavones have a radioprotective effect on the esophagus, mitigating the early and late effects of radiation injury in several esophagus tissue layers. Soy could be administered with radiotherapy to decrease the incidence and severity of esophagitis in lung cancer patients receiving thoracic radiation therapy.

  6. Braun lipoprotein (Lpp) contributes to virulence of yersiniae: potential role of Lpp in inducing bubonic and pneumonic plague.

    Science.gov (United States)

    Sha, Jian; Agar, Stacy L; Baze, Wallace B; Olano, Juan P; Fadl, Amin A; Erova, Tatiana E; Wang, Shaofei; Foltz, Sheri M; Suarez, Giovanni; Motin, Vladimir L; Chauhan, Sadhana; Klimpel, Gary R; Peterson, Johnny W; Chopra, Ashok K

    2008-04-01

    Yersinia pestis evolved from Y. pseudotuberculosis to become the causative agent of bubonic and pneumonic plague. We identified a homolog of the Salmonella enterica serovar Typhimurium lipoprotein (lpp) gene in Yersinia species and prepared lpp gene deletion mutants of Y. pseudotuberculosis YPIII, Y. pestis KIM/D27 (pigmentation locus minus), and Y. pestis CO92 with reduced virulence. Mice injected via the intraperitoneal route with 5 x 10(7) CFU of the Deltalpp KIM/D27 mutant survived a month, even though this would have constituted a lethal dose for the parental KIM/D27 strain. Subsequently, these Deltalpp KIM/D27-injected mice were solidly protected against an intranasally administered, highly virulent Y. pestis CO92 strain when it was given as five 50% lethal doses (LD(50)). In a parallel study with the pneumonic plague mouse model, after 72 h postinfection, the lungs of animals infected with wild-type (WT) Y. pestis CO92 and given a subinhibitory dose of levofloxacin had acute inflammation, edema, and masses of bacteria, while the lung tissue appeared essentially normal in mice inoculated with the Deltalpp mutant of CO92 and given the same dose of levofloxacin. Importantly, while WT Y. pestis CO92 could be detected in the bloodstreams and spleens of infected mice at 72 h postinfection, the Deltalpp mutant of CO92 could not be detected in those organs. Furthermore, the levels of cytokines/chemokines detected in the sera were significantly lower in animals infected with the Deltalpp mutant than in those infected with WT CO92. Additionally, the Deltalpp mutant was more rapidly killed by macrophages than was the WT CO92 strain. These data provided evidence that the Deltalpp mutants of yersiniae were significantly attenuated and could be useful tools in the development of new vaccines.

  7. The impact of microbial immune enteral nutrition on the patients with acute radiation enteritis in bowel function and immune status.

    Science.gov (United States)

    Shao, Feng; Xin, Fu-Ze; Yang, Cheng-Gang; Yang, Dao-Gui; Mi, Yue-Tang; Yu, Jun-Xiu; Li, Guo-Yong

    2014-06-01

    The aim of the study was to investigate the effect of microbial immune enteral nutrition by microecopharmaceutics and deep sea fish oil and glutamine and Peptisorb on the patients with acute radiation enteritis in bowel function and immune status. From June 2010 to January 2013, 46 acute radiation enteritis patients in Liaocheng People's Hospital were randomized into the microbial immune enteral nutrition group and the control group: 24 patients in treatment group and 22 patients in control group. The immune microbial nutrition was given to the study group, but not to the control group. The concentration of serum albumin and prealbumin and the number of CD3 (+) T cell, CD4 (+) T cell, CD8 (+) T cell, CD4 (+)/CD8 (+) and natural killer cell of the two groups were detected on the 1, 7 and 14 days after treatment. The arm muscle circumference and triceps skinfold thickness (TSF) were recorded, and the tolerance of the two groups for enteral nutrition and intestinal symptoms was collected and then comparing the two indicators and get results. The tolerance of microbial immune enteral nutrition group about abdominal pain, bloating and diarrhea was better than the control group (P values were 0.018, 0.04 and 0.008 after 7 days; P values were 0.018, 0.015 and 0.002 after 14 days); and the cellular immune parameters were better than the control group((△) P = 0.008,([Symbol: see text]) P = 0.039, (☆) P = 0.032); No difference was found in nutrition indicators. To the patients with acute radiation enteritis, microbial immune enteral nutrition could improve the patient's immune status, and the tolerance of enteral nutrition could be better for the bowel function and the patients' rehabilitation.

  8. T-bet controls severity of hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    Nance Stephanie C

    2011-06-01

    Full Text Available Abstract Hypersensitivity Pneumonitis (HP is an interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease is characterized by alveolitis, granuloma formation and in some patients' fibrosis. IFNγ plays a critical role in HP; in the absence of IFNγ granuloma formation does not occur. However, recent studies using animal models of HP have suggested that HP is a Th17 disease calling into question the role of IFNγ. In this study, we report that initially IFNγ production is dependent on IL-18 and the transcription factor T-bet, however as the disease continues IFNγ production is IL-18-independent and partially T-bet dependent. Although IFNγ production is required for granuloma formation its role is distinct from that of T-bet. Mice that are deficient in T-bet and exposed to S. rectivirgula develop more severe disease characterized by an exacerbated Th17 cell response, decreased Th1 cell response, and increased collagen production in the lung. T-bet-mediated protection does not appear to be due to the development of a protective Th1 response; shifting the balance from a Th17 predominant response to a Th1 response by inhibition of IL-6 also results in lung pathology. The results from this study suggest that both Th1 and Th17 cells can be pathogenic in this model and that IFNγ and T-bet play divergent roles in the disease process.

  9. Occupational hypersensitivity pneumonitis in a green tea manufacturer.

    Science.gov (United States)

    Tanaka, Yuko; Shirai, Toshihiro; Enomoto, Noriyuki; Asada, Kazuhiro; Oyama, Yoshiyuki; Suda, Takafumi

    2016-04-01

    Hypersensitivity pneumonitis (HP) is caused by numerous agents, and one of its histopathological features is poorly formed granulomas. We report here a rare case of occupational HP caused by green tea, showing well-formed granulomas. The patient, a 54-year-old woman who had worked for 15 years in a green tea factory, was referred for abnormal chest X-ray shadows with cough and breathlessness over a 2-month period. The chest X-ray and high-resolution computed tomography showed diffuse bilateral ground-glass opacities and poorly defined centrilobular nodules. Histopathological examination of the thoracoscopic lung biopsy specimens showed bronchiolocentric interstitial pneumonia with well-formed granulomas. Although the form of granulomas were atypical, laboratory data, CT findings, and intradermal skin testing suggested the diagnosis of subacute HP caused by green tea. After transfer to a different department, her condition improved markedly. Taking a precise medical history and avoidance of the suspected environmental agent proved useful in diagnosing this condition. © 2016 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.

  10. Physiological mechanisms of acute intestinal radiation death. Technical report, 1 June 1983-1 June 1986

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, K.L.; Geraci, J.P.

    1986-06-01

    The overall objective was to clarify the role of fluid and electrolyte loss, bile-duct ligation, radiation-damaged intestinal mucosa, bacterial toxemia and their interrelationships on radiation-induced gastrointestinal death. Using specific pathogen-free CD-1 male rats, this study found that endogenous enteric bacteria did not play a significant role in pure intestinal radiation death. Bile acids, per se, were shown to play little role in intestinal radiation death, but the inability of the denuded mucosa to absorb fluid and electrolytes, thereby producing hypovolemic shock, was the major mechanism.

  11. Coronary CT angiography for acute chest pain triage: Techniques for radiation exposure reduction; 128 vs. 64 multidetector CT

    Energy Technology Data Exchange (ETDEWEB)

    Goitein, Orly; Eshet, Yael; Konen, Eli (Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel)), email: orly.goitein@sheba.health.gov.il; Matetzky, Shlomi (Heart Inst., Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel)); Goitein, David (Surgery C, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel)); Hamdan, Ashraf; Di Segni, Elio (Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel); Heart Inst., Sheba Medical Center, Tel Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ., Tel Aviv (Israel))

    2011-10-15

    Background. Coronary CT angiography (CCTA) is used daily in acute chest pain triage, although exposing patients to significant radiation dosage. CCTA using prospective ECG gating (PG CCTA) enables significant radiation reduction Purpose. To determine whether the routine use of 128 vs. 64 multidetector CT (MDCT) can increase the proportion of patients scanned using PG CCTA technique, lowering radiation exposure, without decreasing image quality. Material and Methods. The study comprised 232 patients, 116 consecutive patients scanned using 128 MDCT (mean age 49 years, 79 men, BMI 28) and 116 consecutive patients (mean age 50 years, 75 men, BMI 28) which were scanned using 64 MDCT. PG CCTA was performed whenever technically permissible by each type of scanner: 64 MDCT = stable heart rate (HR) <60/min and weight <110 kg; 128 MDCT = stable HR < 70/min and weight <140 kg. All coronary segments were evaluated for image quality using a visual scale of 1-5. An estimated radiation dose was recorded. Results. PC CCTA was performed in 84% and 49% of the 128 and 64 MDCT groups, respectively (P < 0.0001). Average image quality score were 4.6 +- 0.3 and 4.7 +- 0.1 for the 128 and 64 MDCT, respectively (P = 0.08). The mean radiation dose exposure was 6.2 +- 4.8 mSv and 10.4 +- 7.5 mSv for the 128 and 64 MDCT, respectively (P = 0.008). Conclusion. The 128 MDCT scanner enables utilization of PG CCTA technique in a greater proportion of patients, thereby decreasing the related radiation significantly, without hampering image quality

  12. Hypersensitivity pneumonitis secondary to lovebirds: a new cause of bird fancier's disease.

    Science.gov (United States)

    Funke, M; Fellrath, J-M

    2008-08-01

    Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease due to the repetitive inhalation of antigens. Most new cases arise from residential exposures, notably to birds, and are thus more difficult to recognise. The present authors report a 59-yr-old male who complained of dyspnoea and cough while being treated with amiodarone. Pulmonary function tests revealed restriction and obstruction with low diffusing lung capacity for carbon monoxide and partial pressure of oxygen. A high-resolution computed tomography chest scan and bronchoalveolar lavage showed diffuse bilateral ground-glass attenuation and lymphocytic alveolitis, respectively. Initial diagnosis was amiodarone pulmonary toxicity, but because of a rapidly favourable evolution, this diagnosis was questioned. A careful environmental history revealed a close contact with lovebirds shortly before the onset of symptoms. Precipitins were strongly positive against lovebird droppings, but were negative against other avian antigens. The patient was diagnosed with hypersensitivity pneumonitis to lovebirds. Avoidance of lovebirds and steroid treatment led to rapid improvement. The present observation identifies a new causative agent for hypersensitivity pneumonitis and highlights the importance of a thorough environmental history and of searching for precipitins against antigens directly extracted from the patient's environment. These two procedures should allow a more precise classification of some cases of pneumonitis, and thus might avoid progression of active undiagnosed hypersensitivity pneumonitis to irreversible fibrosis or emphysema.

  13. Simeprevir with peginterferon and ribavirin induced interstitial pneumonitis: first case report.

    Science.gov (United States)

    Tamaki, Katsuyoshi; Okubo, Akihiko

    2015-01-21

    The effectiveness of hepatitis C treatment has improved with the development of interferon (IFN), and it has drastically improved with the development of peg-interferon-α (PEG-IFN) in combination with ribavirin (RBV) and, more recently, with the addition of a protease inhibitor. Simeprevir, which is a second-generation protease inhibitor, has shown clinically favorable safety and tolerability profiles. Simeprevir received its first global approval in Japan in September 2013 for the treatment of genotype 1 chronic hepatitis C in combination with PEG-IFN and RBV. One serious adverse event associated with IFN therapy is interstitial pneumonitis, which can be fatal. We experienced a patient with interstitial pneumonitis that was induced by simeprevir with PEG-IFN and RBV therapy for chronic hepatitis C in the early stages of therapy (8 wk after initiating therapy). This is the first case report of interstitial pneumonitis with simeprevir with PEG-IFN and RBV in the world. In addition, it is very interesting that the onset of interstitial pneumonitis was earlier than that in conventional PEG-IFN and RBV therapy. This finding suggests that simeprevir augments the adverse event. We present this case report in light of relevant literature on interstitial pneumonitis with conventional PEG-IFN and RBV therapy.

  14. Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation

    Science.gov (United States)

    Sanzari, Jenine K.; Cengel, Keith A.; Wan, X. Steven; Rusek, Adam; Kennedy, Ann R.

    2014-01-01

    NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure. PMID:25202654

  15. Acute hematological effects in mice exposed to the expected doses, dose-rates, and energies of solar particle event-like proton radiation

    Science.gov (United States)

    Sanzari, Jenine K.; Cengel, Keith A.; Steven Wan, X.; Rusek, Adam; Kennedy, Ann R.

    2014-07-01

    NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during an SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hours post-radiation exposure.

  16. Comparative proteomic profiling and possible toxicological mechanism of acute injury induced by carbon ion radiation in pubertal mice testes

    Science.gov (United States)

    Zhang, Hong

    2016-07-01

    We investigated potential mechanisms of acute injury in pubertal mice testes after exposure to carbon ion radiation (CIR). Serum testosterone was measured following whole-body irradiation with a 2Gy carbon ion beam. Comparative proteomic profiling and Western blotting were applied to identify potential biomarkers and measure protein expression, and terminal dUTP nick end-labeling (TUNEL) was performed to detect apoptotic cells. Immunohistochemistry and immunofluorescence were used to investigate protein localization. Serum testosterone was lowest at 24h after CIR, and 10 differentially expressed proteins were identified at this time point that included eIF4E, an important regulator of initiation that combines with mTOR and 4EBP1 to control protein synthesis via the mTOR signalling pathway during proliferation and apoptosis. Protein expression and localization studies confirmed their association with acute injury following exposure to CIR. These three proteins may be useful molecular markers for detecting abnormal spermatogenesis following exposure to environmental and cosmic radiation

  17. Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Lihua [Department of Radiation Oncology, The First Hospital of Jilin University, Changchun (China); Cui, Jingkun [Department of Internal Medicine, Nanling School District Hospital of Jilin University, Changchun (China); Tang, Fengjiao; Cong, Xiaofeng [Cancer Center, The First Hospital of Jilin University, Changchun (China); Han, Fujun, E-mail: fujun_han@aliyun.com [Cancer Center, The First Hospital of Jilin University, Changchun (China)

    2015-04-01

    Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATM polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was

  18. A method to adjust radiation dose-response relationships for clinical risk factors

    DEFF Research Database (Denmark)

    Appelt, Ane Lindegaard; Vogelius, Ivan R

    2012-01-01

    Several clinical risk factors for radiation induced toxicity have been identified in the literature. Here, we present a method to quantify the effect of clinical risk factors on radiation dose-response curves and apply the method to adjust the dose-response for radiation pneumonitis for patients...

  19. The pathology of ionizing radiation as defined by morphologic patterns

    Energy Technology Data Exchange (ETDEWEB)

    Fajardo, Luis Felipe [Stanford Univ. School of Medicine and Veterans Affairs Health Care System, Palo Alto, CA (United States)

    2005-02-01

    This article presents a brief description of the effects of ionizing radiation in human tissues, as seen by the Pathologist. The lesions that occur in multiple organ/tissues will be discussed, dividing them into those that affect (a) the parenchyma or epithelia, (b) the stromal elements, and (c) the blood vessels. Since not all lesions fit into these patterns, the exceptions will be described as characteristic organ lesions. Unless specified otherwise the alterations presented are those that result from electromagnetic radiation (x-rays and gamma rays) as used for clinical radiation therapy. Most of the material presented will be delayed injury (i.e. months-to-years after exposure). The epithelial/parenchymal lesions include atrophy, necrosis, metaplasia, cellular atypia, dysplasia, and neoplasia. The common stromal lesions--the best recognized by pathologists--include fibrosis, fibrinous exudates, necrosis (with a paucity of cellular inflammatory exudates), and atypical fibroblasts. The vascular lesions are quite consistent: most often they affect the microvessels (capillaries, sinusoids) producing lethal and sublethal damage to the endothelial cells, with capillary rupture or thrombosis. Medium-size vessels show neointimal proliferation, fibrinoid necrosis, thrombosis, or acute arteritis. Damage in large vessels is less common; it occurs more in arteries than in veins and includes neointimal proliferation, atheromatosis, thrombosis and rupture (a dramatic complication). Some of the characteristic organ lesions are veno-occlusive liver disease, acute radiation pneumonitis, permanent bone marrow hypoplasia or aplasia, and colitis cystica profunda. Neoplasms are a well-recognized delayed complication of radiation and will not be described in detail. It is important to remember that there are no pathognomonic features of injuries produced by ionizing radiation. Nonetheless, although not specific individually, the combined features are characteristic enough to be

  20. Association of elevated radiation dose with mortality in patients with acute myocardial infarction undergoing percutaneous coronary intervention

    Energy Technology Data Exchange (ETDEWEB)

    Parikh, Puja B.; Prakash, Sheena; Tahir, Usman; Kort, Smadar; Gruberg, Luis; Jeremias, Allen, E-mail: allen.jeremias@stonybrook.edu

    2014-09-15

    Objectives: This study sought to identify clinical and procedural predictors of elevated radiation dose received by patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) and to determine if elevated radiation dose was predictive of mortality in this population. Background: Little data exist regarding the impact of excessive radiation burden on clinical outcomes in patients undergoing PCI. Methods: The study population included 1,039 patients who underwent PCI for an AMI between January 1, 2007 and December 31, 2008 at an academic tertiary care teaching hospital. Cumulative skin dose (measured in milligray [mGy]) was selected as a measurement of patient radiation burden. Clinical and procedural variables were analyzed in multiple logistic and linear regression models to determine predictors of higher skin dose, and its impact was evaluated on all-cause intermediate-term mortality at two years. Results: Median skin dose was 2120 mGy (IQR 1379–3190 mGy) in the overall population, of which 153 (20.8%) patients received an elevated skin dose (defined as a skin dose > 4,000 mGy). Independent predictors of elevated skin dose included male gender, obesity, multivessel intervention, and presentation with a non-ST-elevation MI (NSTEMI) versus an ST-elevation MI (STEMI). Increased skin dose was not predictive of intermediate-term mortality by multivariate analysis in the overall population or in either subgroup of STEMI and NSTEMI. Conclusions: In this contemporary observational study examining patients with AMI undergoing PCI, male gender, obesity, multivessel intervention, and presentation with a NSTEMI were associated with increased radiation exposure.

  1. Pneumonite de hipersensibilidade ao tabaco Hypersensitivity pneumonitis to tobacco

    Directory of Open Access Journals (Sweden)

    SÍLVIA E.C. MACEDO

    2001-01-01

    Full Text Available Pneumonite de hipersensibilidade (PH é decorrente da inalação de antígenos orgânicos e/ou inorgânicos por indivíduos suscetíveis. Relata-se o caso de uma mulher de 18 anos, plantadora de tabaco em Pelotas, no Sul do Brasil, com dispnéia progressiva, tosse seca e emagrecimento havia 35 dias. Apresentava crepitações finas no tórax e a radiografia evidenciou infiltrado intersticial difuso. O diagnóstico de PH foi estabelecido pela história de exposição, achados tomográficos e exame anatomopatológico de pulmão obtido por biópsia a céu aberto. Estabeleceram-se como causa antígenos provenientes do cultivo de tabaco. Com prednisona e o afastamento do plantio do tabaco houve boa resposta clínica e funcional.Hypersensitivity pneumonitis (HP derives from the inhalation of organic and/or inorganic antigens by susceptible individuals. The authors report the case of an eighteen-year-old female, who worked as a tobacco planter in Pelotas, southern Brazil. She had been presenting progressive dyspnea, dry cough, and weight loss for 35 days. She had fine thoracic crepitations and X-ray examination revealed diffuse interstitial infiltration. The diagnosis of HP was determined by her history of exposure to tobacco, tomographic findings and anatomopathologic examination of the lung, obtained by open biopsy. Tobacco antigens were found to be the cause. As patient was treated with prednisone and tobacco exposure was discontinued, a good clinic and functional response was observed.

  2. Two Cases of Nivolumab Re-Administration after Pneumonitis as Immune-Related Adverse Events

    Directory of Open Access Journals (Sweden)

    Keisuke Imafuku

    2017-04-01

    Full Text Available Nivolumab is a recently approved medication for the treatment of unresectable malignant melanoma. Many immune-related adverse events (irAEs associated with nivolumab have been reported, such as pneumonitis, hepatitis, dermatitis, and thyroiditis. Prednisolone can effectively treat irAEs. However, it is unclear how or if nivolumab should be administered to patients after they have experienced an irAE. Herein, we show 2 patients who underwent pneumonitis as irAE. Case 1 demonstrated a cryptogenic organizing pneumonia pattern in the CT scan and case 2 had a diffuse alveolar damage (DAD pattern. Oral corticosteroids improved chest shadow of CT scan in both cases. However, when nivolumab was re-administrated, case 1 demonstrated no symptoms, but case 2 demonstrated pneumonia again. From our cases, it is difficult to re-administrate nivolumab for the patients with pneumonitis which shows a DAD pattern in CT, even if oral corticosteroids improve their symptoms.

  3. Clinical features, diagnostic challenges, and management strategies in checkpoint inhibitor-related pneumonitis.

    Science.gov (United States)

    Chuzi, Sarah; Tavora, Fabio; Cruz, Marcelo; Costa, Ricardo; Chae, Young Kwang; Carneiro, Benedito A; Giles, Francis J

    2017-01-01

    Immune checkpoint inhibitors, including cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) inhibitors, represent an effective treatment modality for multiple malignancies. Despite the exciting clinical benefits, checkpoint inhibition is associated with a series of immune-related adverse events (irAEs), many of which can be life-threatening and result in significant treatment delays. Pneumonitis is an adverse event of special interest as it led to treatment-related deaths in early clinical trials. This review summarizes the incidence of pneumonitis during treatment with the different checkpoint inhibitors and discusses the prognostic significance of tumor type. The wide range of clinical, radiographic, and histologic characteristics of checkpoint inhibitor-related pneumonitis is reviewed and followed by guidance on the different management strategies.

  4. Oral hygiene care of patients with oral cancer during postoperative irradiation. An alleviating effect on acute radiation mucositis

    Energy Technology Data Exchange (ETDEWEB)

    Katsura, Kouji; Masuko, Noriko; Hayashi, Takafumi [Niigata Univ. (Japan). School of Dentistry; Sugita, Tadashi; Sakai, Kunio; Tsuchida, Emiko; Matsumoto, Yasuo; Sasamoto, Ryuta

    2000-09-01

    To evaluate the effect of oral hygiene care of patients with oral cancer on alleviating acute radiation mucositis. Eighteen patients receiving postoperative radiotherapy for tongue and oral floor cancer were evaluated. Radiotherapy was given in 2 Gy per fraction, 5 times a week for a total dose of 50 Gy in most patients. Radiation field included the tongue and oral floor. During radiotherapy, 8 patients were treated by dento-maxillofacial radiologists with special concern on oral hygiene (oral hygiene group) and the remaining 10 patients were treated with routine dental care (standard medication group). Mucositis were evaluated using JCOG grade and EORTC/RTOG score by radiotherapists or dento-maxillofacial radiologists at 10 Gy intervals. Oral hygiene plans comprised motivation to maintain oral hygiene and establishing the habits of oral self care 4 times per day. Once a week, oral hygiene and oral cleaning of patients were checked by dento-maxillofacial radiologists. Oral self care included mechanical tooth brushing and a chemical mouthwash. No patients with grade 3 and score 4 mucositis were noted in the oral hygiene group. Severe mucositis occurred less frequently in the oral hygiene group than in the standard medication group. Interruption of radiotherapy due to severe mucositis did not occur in the oral hygiene group. On the other hand, interruption of radiotherapy occurred in four patients in the standard medication group, and in three it was due to severe oral pain. Our results suggested that our method of oral hygiene was more effective for alleviating acute radiation mucositis than other methods so far reported. In addition, our method is considered to be useful in preventing rampant dental caries and severe periodontitis due to the xerostomia induced by radiotherapy. (author)

  5. Therapeutics interventions with anti-inflammatory creams in post radiation acute skin reactions: a systematic review of most important clinical trials.

    Science.gov (United States)

    Koukourakis, Georgios V; Kelekis, Nikolaos; Kouvaris, John; Beli, Ivelina K; Kouloulias, Vassilios E

    2010-06-01

    The majority of cancer patients will receive radiation therapy treatment at some stage during their malignancy. An acute skin reaction represents a common post radiation side effect with different grade of severity. In order to investigate the optimal methods to prevent and manage acute skin reactions related to radiation therapy we have conducted a systematic review on this topic. It seems that skin washing, including gentle washing with water alone with or without mild soap, should be permitted in patients receiving radiation therapy, to prevent acute skin reaction. In addition, a low dose (i.e., 1%) corticosteroid cream may be beneficial in the reduction of itching and irritation. We have concluded that there is insufficient evidence to support or refute specific topical or oral agents for the prevention or management of acute skin reaction. There is a need for further research to review treatments that have produced promising results in the reviewed research studies and to evaluate other commonly recommended topical treatments. The purpose of this patent and literature review is to advocate the current management of acute skin reaction.

  6. Acute Radiation-Induced Nocturia in Prostate Cancer Patients Is Associated With Pretreatment Symptoms, Radical Prostatectomy, and Genetic Markers in the TGF{beta}1 Gene

    Energy Technology Data Exchange (ETDEWEB)

    De Langhe, Sofie, E-mail: Sofie.DeLanghe@UGent.be [Department of Basic Medical Sciences, Ghent University, Gent (Belgium); De Ruyck, Kim [Department of Basic Medical Sciences, Ghent University, Gent (Belgium); Ost, Piet; Fonteyne, Valerie [Department of Radiation Oncology, Ghent University Hospital, Gent (Belgium); Werbrouck, Joke [Department of Basic Medical Sciences, Ghent University, Gent (Belgium); De Meerleer, Gert; De Neve, Wilfried [Department of Radiation Oncology, Ghent University Hospital, Gent (Belgium); Thierens, Hubert [Department of Basic Medical Sciences, Ghent University, Gent (Belgium)

    2013-02-01

    Purpose: After radiation therapy for prostate cancer, approximately 50% of the patients experience acute genitourinary symptoms, mostly nocturia. This may be highly bothersome with a major impact on the patient's quality of life. In the past, nocturia is seldom reported as a single, physiologically distinct endpoint, and little is known about its etiology. It is assumed that in addition to dose-volume parameters and patient- and therapy-related factors, a genetic component contributes to the development of radiation-induced damage. In this study, we investigated the association among dosimetric, clinical, and TGF{beta}1 polymorphisms and the development of acute radiation-induced nocturia in prostate cancer patients. Methods and Materials: Data were available for 322 prostate cancer patients treated with primary or postoperative intensity modulated radiation therapy (IMRT). Five genetic markers in the TGF{beta}1 gene (-800 G>A, -509 C>T, codon 10 T>C, codon 25 G>C, g.10780 T>G), and a high number of clinical and dosimetric parameters were considered. Toxicity was scored using an symptom scale developed in-house. Results: Radical prostatectomy (P<.001) and the presence of pretreatment nocturia (P<.001) are significantly associated with the occurrence of radiation-induced acute toxicity. The -509 CT/TT (P=.010) and codon 10 TC/CC (P=.005) genotypes are significantly associated with an increased risk for radiation-induced acute nocturia. Conclusions: Radical prostatectomy, the presence of pretreatment nocturia symptoms, and the variant alleles of TGF{beta}1 -509 C>T and codon 10 T>C are identified as factors involved in the development of acute radiation-induced nocturia. These findings may contribute to the research on prediction of late nocturia after IMRT for prostate cancer.

  7. Biological dosimetry by the triage dicentric chromosome assay: potential implications for treatment of acute radiation syndrome in radiological mass casualties.

    Science.gov (United States)

    Romm, Horst; Wilkins, Ruth C; Coleman, C Norman; Lillis-Hearne, Patricia K; Pellmar, Terry C; Livingston, Gordon K; Awa, Akio A; Jenkins, Mark S; Yoshida, Mitsuaki A; Oestreicher, Ursula; Prasanna, Pataje G S

    2011-03-01

    Biological dosimetry is an essential tool for estimating radiation dose. The dicentric chromosome assay (DCA) is currently the tool of choice. Because the assay is labor-intensive and time-consuming, strategies are needed to increase throughput for use in radiation mass casualty incidents. One such strategy is to truncate metaphase spread analysis for triage dose estimates by scoring 50 or fewer metaphases, compared to a routine analysis of 500 to 1000 metaphases, and to increase throughput using a large group of scorers in a biodosimetry network. Previously, the National Institutes for Allergies and Infectious Diseases (NIAID) and the Armed Forces Radiobiology Research Institute (AFRRI) sponsored a double-blinded interlaboratory comparison among five established international cytogenetic biodosimetry laboratories to determine the variability in calibration curves and in dose measurements in unknown, irradiated samples. In the present study, we further analyzed the published data from this previous study to investigate how the number of metaphase spreads influences dose prediction accuracy and how this information could be of value in the triage and management of people at risk for the acute radiation syndrome (ARS). Although, as expected, accuracy decreased with lower numbers of metaphase spreads analyzed, predicted doses by the laboratories were in good agreement and were judged to be adequate to guide diagnosis and treatment of ARS. These results demonstrate that for rapid triage, a network of cytogenetic biodosimetry laboratories can accurately assess doses even with a lower number of scored metaphases.

  8. Rectal planning risk volume correlation with acute and late toxicity in 3-dimensional conformal radiation therapy for prostate cancer.

    Science.gov (United States)

    Dias, R S; Giordani, A J; Souhami, L; Segreto, R A; Segreto, H R C

    2011-12-01

    The purpose of this study was to evaluate rectum motion during 3-Dimensional conformal radiation therapy (3D-CRT) in prostate cancer patients, to derive a planning volume at risk (PRV) and to correlate the PRV dose-volume histograms (DVH) with treatment complications.This study was conducted in two phases. Initially, the PRV was defined prospectively in 50 consecutive prostate cancer patients (Group 1) who received a radical course of 3-D CRT. Then, the obtained PRV was used in the radiotherapy planning of these same 50 patients plus another 59 prostate cancer patients (Group 2) previously treated between 2004 and 2008. All these patients' data, including the rectum and PRV DVHs, were correlated to acute and late complications, according to the Common Toxicity Criteria (CTC) v4.0.The largest displacement occurred in the anterior axis. Long-term gastrointestinal (GI) complications grade ≥ 2 were seen in 9.2% of the cases. Factors that influenced acute GI reactions were: doses at 25% (p 5 0.011) and 40% (p 5 0.005) of the rectum volume and at 40% of the PRV (p 5 0.012). The dose at 25% of the rectum volume (p 5 0.033) and acute complications ≥ grade 2 (p 5 0.018) were prognostic factors for long-term complications. The PRV DVH did not correlate with late toxicity. The rectum showed a significant inter-fraction motion during 3D-CRT for prostate cancer. PRV dose correlated with acute gastrointestinal complications and may be a useful tool to predict and reduce their occurrence.

  9. Diagnosis and management of interstitial pneumonitis associated with interferon therapy for chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Interstitial pneumonitis(IP) is an uncommon pulmonary complication associated with interferon(IFN) therapy for chronic hepatitis C virus(HCV) infection.Pneumonitis can occur at any stage of HCV treatment,ranging from 2 to 48 wk,usually in the first 12 wk.Its most common symptoms are dyspnoea,dry cough,fever,fatigue,arthralgia or myalgia,and anorexia,which are reversible in most cases after cessation of IFN therapy with a mean subsequent recovery time of 7.5 wk.Bronchoalveolar lavage in combination with ches...

  10. Drug-induced interstitial pneumonitis due to low-dose lenalidomide.

    Science.gov (United States)

    Kunimasa, Kei; Ueda, Tomoaki; Arita, Machiko; Maeda, Takeshi; Hotta, Machiko; Ishida, Tadashi

    2012-01-01

    Lenalidomide is a second-generation immunomodulatory drug that has been approved to treat relapsed or refractory multiple myeloma. Here, we describe a patient who was treated with a low dose of lenalidomide (5 mg/day on days 1-21 of a 28-day cycle) because the standard dose of bortezomib was too toxic and adverse events persisted. However, he developed fever, dyspnea, hypoxia and pulmonary infiltrates. The results of an extensive workup for other causes including infections were negative and the final diagnosis was lenalidomide-induced interstitial pneumonitis. This is the first case report of lenalidomide-induced pneumonitis in a Japanese patient.

  11. Pneumonitis and pulmonary fibrosis in a patient receiving adjuvant docetaxel and cyclophosphamide for stage 3 breast cancer: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Ochoa Roberto

    2012-11-01

    Full Text Available Abstract Introduction Pulmonary toxicities associated with chemotherapeutic agents utilized as adjuvant therapy in patients with breast cancer are distinctly uncommon. The chemotherapy regimen of docetaxel/cyclophosphamide has a more favorable therapeutic index compared to anthracycline-based regimens due to a significantly lower incidence of heart failure and leukemia. Consequently, docetaxel/cyclophosphamide is the preferred adjuvant chemotherapy of choice in older women or in women where anthracyclines may be contraindicated. Pulmonary complications in patients with breast cancer receiving taxane-based adjuvant chemotherapy in the absence of radiation are distinctly uncommon. Here, we report the case of a patient receiving adjuvant docetaxel/cyclophosphamide who developed rapid-onset, biopsy-proven interstitial pneumonitis. Case presentation A 72-year-old Hispanic woman was diagnosed as having stage 3 hormone-receptor positive, human epidermal growth factor receptor 2/neu negative, invasive breast cancer. Due to the estimated 10-year risk of recurrence of approximately 80 percent, a decision was made to treat our patient with adjuvant chemotherapy. Due to her age and increased risk of cardiac toxicity with anthracycline-based chemotherapy regimens, our patient was treated with docetaxel/cyclophosphamide chemotherapy for a total of four planned cycles. However, approximately two weeks after receiving the third cycle of chemotherapy, our patient developed rapidly progressive dyspnea, and a non-productive cough and went to the emergency room at an outside medical facility. She was found to have mild hypoxemia, and new onset of peripheral, subpleural fibrotic changes not present on pre-treatment scans. A thorascopic-guided wedge biopsy of the lung tissue revealed subacute interstitial pneumonitis. Our patient made a rapid clinical recovery after treatment with corticosteroids. Conclusions Interstitial pneumonitis is a rare complication of

  12. Expression of ICAM-1 and acute inflammatory cell infiltration in the early phase of radiation colitis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Yuji; Ito, Masahiro; Matsuu, Mutsumi; Shichijo, Kazuko; Fukuda, Eiichiro; Nakayama, Toshiyuki; Nakashima, Masahiro; Naito, Shinji; Sekine, Ichiro [Nagasaki Univ. (Japan). Atomic Bomb Disease Inst.

    2000-09-01

    Inflammatory cell infiltration of the colon is observed at an early stage of radiation-induced colitis. The emigration of inflammatory cells from the circulation requires interactions between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. To elucidate this process, the present work analyzes the kinetics of the expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation of inflammatory myeloperoxidase (MPO)-positive cells in relation to the appearance of acute radiation colitis prior to an overt radiation-induced ulcer. Colon tissues were obtained from Wistar Kyoto rats at various times after 22.5 Gy irradiation to the rectum. Histologically, crypt depletion and numerous inflammatory cells were observed 4 days after irradiation, and mucosal ulcer 6 days after irradiation. ICAM-1 immunopositivity was present in the endothelial cells of small vessels in the mucosa of both control and irradiated rats. ICAM-1 mRNA expression was detected in normal colon and irradiated colon by reverse transcription-PCR. In Northern blotting, ICAM-1 mRNA levels were found to increase markedly in the irradiated colon compared to the normal colon. In Western blotting, ICAM-1 protein expression also increased with a peak one day after irradiation, and remained elevated up to 6 days thereafter. The number of MPO-positive cells in lamina propria mucosa increased in a time-dependent fashion from 6 h to 6 days after irradiation. These data suggest that up-regulation of ICAM-1 in endothelial cells and accumulation of MPO positive cells play important roles in the development of radiation-induced colonic ulcer. (author)

  13. Preventive central nervous system irradiation in children with acute nonlymphocytic leukemia. [Complications of. gamma. radiation

    Energy Technology Data Exchange (ETDEWEB)

    Dahl, G.V.; Simone, J.V.; Hustu, H.O.; Mason, C.

    1978-11-01

    In this study of children with acute nonlymphocytic leukemia an attempt was made to prevent central nervous system relapse and to determine whether this therapy, coupled with multiagent chemotherapy, would be successful in prolonging durations of complete remission. Central nervous system relapses were prevented by irradiation, although patients who received this therapy did no better than those who did not receive irradiation. A small group of patients received irradiation to the liver and spleen, but this modality also failed to improve the duration of remission. Control of extramedullary leukemia, in this study, failed to improve remission duration because bone marrow relapse was not prevented or delayed. It is unlikely that focal therapy will have a significant impact in acute nonlymphocytic leukemia until longer marrow remissions are achieved.

  14. BM-16INCREASED ACUTE RADIATION EFFECT (ARE) WITH IPILUMUMAB AND RADIOSURGERY IN PATIENTS WITH MELANOMA BRAIN METASTASES

    Science.gov (United States)

    Khoja, Leila; Kurtz, Goldie; Zadeh, Gelareh; Laperriere, Normand; Menard, Cynthia; Millar, Barbara-Ann; Bernstein, Mark; Kongkham, Paul; Joshua, Anthony; Hogg, David; Butler, Marcus; Chung, Caroline

    2014-01-01

    BACKGROUND: Ipilumumab (Ipi), an antibody that enhances T-cell activation, has been shown to improve survival in patients with metastatic melanoma. Ipilumumab may have synergistic effects with radiotherapy but this may result in increased toxicity. This study investigated the incidence of acute radiation effect (ARE) in patients with melanoma brain metastases treated with Ipi and radiosurgery (SRS) or whole brain radiotherapy (WBRT). METHODOLOGY: This retrospective study included metastatic melanoma patients treated at our institution from 2008-2013 who received SRS or WBRT for brain metastases within 4 months of Ipi treatment. We evaluated the incidence, timing and factors associated with acute radiation effect (ARE). RESULTS: From 159 patients treated with Ipi, 22 patients also received brain RT within 4 months of treatment. Three patients were excluded for lack of follow-up brain imaging, thus 19 were analysed: 14 males and 5 females, with median age 58 years (range 24-82). Ten were treated with SRS, 7 with WBRT, and 2 with SRS plus WBRT. Median dose for SRS was 21 Gy (range: 15-24 Gy). Five of 13 patients treated with SRS (38%) experienced symptomatic edema requiring steroids within 1 month of starting Ipi, and within 4 months of RT. One patient had a haemorrhage and 1 required surgical resection, which demonstrated viable disease. Therefore 3 patients (23%) treated with SRS developed isolated ARE. These metastases had volumes less than 4.2 cm3 and were treated within 4 months of Ipi to a median dose of 19.5 Gy (range 15-21 Gy). No patients with WBRT alone developed ARE. CONCLUSIONS: Following SRS for brain mets and Ipi, ARE was seen in 23% of patients within 4 months of starting Ipi treatment. This is greater than the commonly reported 10% risk of ARE after SRS alone for brain metastasis. No increased toxicity was seen with WBRT and Ipi.

  15. Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Wortel, Ruud C.; Incrocci, Luca [Department of Radiation Oncology, Erasmus Medical Center Cancer Institute, Rotterdam (Netherlands); Pos, Floris J.; Lebesque, Joos V.; Witte, Marnix G.; Heide, Uulke A. van der; Herk, Marcel van [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Heemsbergen, Wilma D., E-mail: w.heemsbergen@nki.nl [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands)

    2015-03-15

    Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicity questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.

  16. SU-E-P-18: Intensity-Modulated Radiation Therapy for Cervical Esophageal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bai, W; Qiao, X; Zhou, Z; Song, Y; Zhang, R; Zhen, C [The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei (China)

    2015-06-15

    Purpose: To retrospectively analyze the outcomes and prognostic factors of cervical esophageal squamous cell carcinoma (SCC) treated with intensity modulated radiation therapy (IMRT). Methods: Thirty-seven patients with cervical esophageal SCC treated with IMRT were analyzed retrospectively. They received 54–66 Gy in 27–32 fractions. Nineteen patients received concurrent (n=12) or sequential (n=7) platinum-based two drugs chemoradiotherapy. Overall survival (OS), local control rates (LCR) and prognostic factors were evaluated. Acute toxicities and patterns of first failures were observed. Results: The median follow-up was 46 months for alive patients. The l-, 3-, 4- and 5-year OS of the all patients were 83.8%, 59.1%, 47.5% and 32.6% respectively. The median survival time was 46 months. The l-, 3-,4- and 5-year LCR were 82.9%, 63.0%, 54.5% and 54.5%, respectively. Univariate and Multivariate analysis all showed that size of GTV was an independent prognostic factor (p=0.033, p=0.039). There were no patients with Grade 3 acute radiation esophagitis and Grade 2–4 acute pneumonitis. The local failure accounted for 70.0% of all treatment-related failures. Conclusion: IMRT is safe and effective in the treatment of cervical esophageal squamous cell carcinoma. Size of GTV is an independent prognostic factor. Local failure still remains the main reason of treatment failures. The authors declare no conflicts of interest in preparing this article.

  17. Effect of corticosteroid treatment on cell recovery by lung lavage in acute radiation-induced lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Wesselius, L.J.; Floreani, A.A.; Kimler, B.F.; Papasian, C.J.; Dixon, A.Y. (Kansas City Veterans Administration Medical Center, MO (USA))

    1989-11-01

    The purpose of this study was to quantitate cell populations recovered by lung lavage up to 6 weeks following thoracic irradiation (24 Gy) as an index of the acute inflammatory response within lung structures. Additionally, rats were treated five times weekly with intraperitoneal saline (0.3 cc) or methylprednisolone (7.5 mg/kg/week). Lung lavage of irradiated rats recovered increased numbers of total cells compared to controls beginning 3 weeks after irradiation (P less than 0.05). The initial increase in number of cells recovered was attributable to an influx of neutrophils (P less than 0.05), and further increases at 4 and 6 weeks were associated with increased numbers of recovered macrophages (P less than 0.05). Lung lavage of steroid-treated rats at 6 weeks after irradiation recovered increased numbers of all cell populations compared to controls (P less than 0.05); however, numbers of recovered total cells, macrophages, neutrophils, and lymphocytes were all significantly decreased compared to saline-treated rats (P less than 0.05). The number of inflammatory cells recovered by lung lavage during acute radiation-induced lung injury is significantly diminished by corticosteroid treatment. Changes in cells recovered by lung lavage can also be correlated with alteration in body weight and respiration rate subsequent to treatment with thoracic irradiation and/or corticosteroids.

  18. Sodium butyrate enemas in the treatment of acute radiation-induced proctitis in patients with prostate cancer and the impact on late proctitis. A prospective evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Hille, Andrea; Herrmann, Markus K.A.; Kertesz, Tereza; Christiansen, Hans; Hermann, Robert M.; Hess, Clemens F. [University Hospital, Goettingen (Germany). Department of Radiotherapy and Radiooncology; Pradier, Olivier [University Hospital, Brest (France). Department of Radiotherapy and Radiooncology; Schmidberger, Heinz [University Hospital, Mainz (Germany). Department of Radiotherapy and Radiooncology

    2008-12-15

    To evaluate prospectively the effect of sodium butyrate enemas on the treatment of acute and the potential influence on late radiation-induced proctitis. 31 patients had been treated with sodium butyrate enemas for radiation-induced acute grade II proctitis which had developed after 40 Gy in median. During irradiation the toxicity was evaluated weekly by the Common Toxicity Criteria (CTC) and subsequently yearly by the RTOG (Radiation Therapy Oncology Group) and LENT-SOMA scale. 23 of 31 patients (74%) experienced a decrease of CTC grade within 8 days on median. A statistical significant difference between the incidence and the severity of proctitis before start of treatment with sodium butyrate enemas compared to 14 days later and compared to the end of irradiation treatment course, respectively, was found. The median follow-up was 50 months. Twenty patients were recorded as suffering from no late proctitis symptom. Eleven patients suffered from grade I and 2 of these patients from grade II toxicity, too. No correlation was seen between the efficacy of butyrate enemas on acute proctitis and prevention or development of late toxicity, respectively. Sodium butyrate enemas are effective in the treatment of acute radiation-induced proctitis in patients with prostate cancer but have no impact on the incidence and severity of late proctitis. (orig.)

  19. Timed Get Up and Go Test and Geriatric 8 Scores and the Association With (Chemo-) Radiation Therapy Noncompliance and Acute Toxicity in Elderly Cancer Patients

    NARCIS (Netherlands)

    Middelburg, Judith G.; Mast, Mirjam E.; de Kroon, Maaike; Jobsen, Jan J.; Rozema, Tom; Maas, Huub A. A. M.; Baartman, Elizabet A.; Geijsen, Debby; van der Leest, Annija H.; van den Bongard, Desiree J.; van Loon, Judith; Budiharto, Tom; Coebergh, Jan-Willem; Aarts, Mieke J; Struikmans, Henk

    2017-01-01

    Purpose: To investigate whether the Geriatric 8 (G8) and the Timed Get Up and Go Test (TGUGT) and clinical and demographic patient characteristics were associated with acute toxicity of radiation therapy and noncompliance in elderly cancer patients being irradiated with curative intent. Methods and

  20. Characterization of the rat pneumonic plague model: infection kinetics following aerosolization of Yersinia pestis CO92.

    Science.gov (United States)

    Agar, Stacy L; Sha, Jian; Foltz, Sheri M; Erova, Tatiana E; Walberg, Kristin G; Baze, Wallace B; Suarez, Giovanni; Peterson, Johnny W; Chopra, Ashok K

    2009-02-01

    Yersinia pestis, the causative agent of human bubonic and pneumonic plague, is spread during natural infection by the fleas of rodents. Historically associated with infected rat fleas, studies on the kinetics of infection in rats are surprisingly few, and these reports have focused mainly on bubonic plague. Although the natural route of primary infection results in bubonic plague in humans, it is commonly thought that aerosolized Y. pestis will be utilized during a biowarfare attack. Accordingly, based on our previous characterization of the mouse model of pneumonic plague, we sought to examine the progression of infection in rats exposed in a whole-body Madison chamber to aerosolized Y. pestis CO92. Following an 8.6 LD(50) dose of Y. pestis, injury was apparent in the rat tissues based on histopathology, and chemokines and cytokines rose above control levels (1h post infection [p.i.]) in the sera and organ homogenates over a 72-h infection period. Bacteria disseminated from the lungs to peripheral organs, with the largest increases in the spleen, followed by the liver and blood at 72h p.i. compared to the 1h controls. Importantly, rats were as sensitive to pneumonic plague as mice, having a similar LD(50) dose by the intranasal and aerosolized routes. Further, we showed direct transmission of plague bacteria from infected to uninfected rats. Taken together, the data allowed us to characterize for the first time a rat pneumonic plague model following aerosolization of Y. pestis.

  1. [Primary pneumonic plague with nosocomial transmission in La Libertad, Peru 2010].

    Science.gov (United States)

    Donaires, Luis F; Céspedes, Manuel; Valencia, Pedro; Salas, Juan Carlos; Luna, María E; Castañeda, Alex; Peralta, Víctor; Cabezas, César; Pachas, Paul E

    2010-09-01

    Pneumonic plague is one of the clinical forms of plague, of low frequency and high mortality, transmitted by direct inhalation of Yersinia pestis coming from an animal or from person to person. To describe the clinical and epidemiological characteristics of the cases of primary pneumonic plague in an outbreak in the north of Peru. The clinical records of the confirmed cases of primary pneumonic plague presenting in an outbreak occurring in La Libertad, in July 2010, were reviewed, also the search and contact investigation was performed. The index case was identified, as well as three additional cases, out of these, two were nosocomial infections related to the index case. The initial clinical presentation was characterized by sudden onset of fever, chills, myalgia and chest pain, which in less than 24 hours evolved to hypotension and cyanosis. The initiation of specific treatment varied from 2 to 12 days, and cases with prompt initiation of treatment had a better clinical outcome. The lethality was 50% (2/4). Nosocomial transmission of pneumonic plague in Peru is evidenced, with severe clinical manifestations and high lethality.

  2. Clinical features, diagnostic challenges, and management strategies in checkpoint inhibitor-related pneumonitis

    Directory of Open Access Journals (Sweden)

    Chuzi S

    2017-06-01

    Full Text Available Sarah Chuzi,1 Fabio Tavora,2 Marcelo Cruz,3 Ricardo Costa,3 Young Kwang Chae,3 Benedito A Carneiro,3 Francis J Giles3 1Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; 2Argos Laboratory, Messejana Heart and Lung Hospital, Fortaleza, Brazil; 3Developmental Therapeutics Program, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Abstract: Immune checkpoint inhibitors, including cytotoxic T-lymphocyte antigen 4 (CTLA-4 and programmed cell death-1 (PD-1 inhibitors, represent an effective treatment modality for multiple malignancies. Despite the exciting clinical benefits, checkpoint inhibition is associated with a series of immune-related adverse events (irAEs, many of which can be life-threatening and result in significant treatment delays. Pneumonitis is an adverse event of special interest as it led to treatment-related deaths in early clinical trials. This review summarizes the incidence of pneumonitis during treatment with the different checkpoint inhibitors and discusses the prognostic significance of tumor type. The wide range of clinical, radiographic, and histologic characteristics of checkpoint inhibitor-related pneumonitis is reviewed and followed by guidance on the different management strategies. Keywords: immune checkpoint inhibitors, pneumonitis, anti-PD-1, anti-CTLA-4, immune-related adverse event

  3. Cranial radiation for pediatric T-lineage acute lymphoblastic leukemia: a systematic review and meta-analysis.

    Science.gov (United States)

    Kelly, Michael J; Trikalinos, Thomas A; Dahabreh, Issa J; Gianferante, Matthew; Parsons, Susan K

    2014-10-01

    There are heterogeneous approaches to cranial radiation therapy (CRT) for T-lineage acute lymphoblastic leukemia (T-ALL). We performed a systematic review of studies that specified a radiation strategy and reported survival for pediatric T-ALL. Our analysis included 62 publications reporting 78 treatment groups (patient n = 5844). The average event-free survival (EFS) was higher by 6% per 5 years (P reference group (CRT for all) which had a year-adjusted EFS of 65% (95% confidence interval, CI: 61-69%) the adjusted EFS was significantly worse (rate difference (RD) = -9%, 95% CI: -15 to -2%) among studies that used a risk-directed approach to CRT (P = 0.004). The adjusted EFS for the other strategies were not significantly different compared to the reference group: CRT for central nervous system positive patients only (RD = -3%, 95% CI: -14 to 7%, P = 0.49); CRT omitted for all patients (RD = 5%, 95% CI: -4 to 15%, P = 0.33). CRT may not be necessary with current chemotherapy for T-ALL. These findings, however, are susceptible to bias and caution should be applied in drawing conclusions on the comparative effectiveness of alternative CRT strategies.

  4. An adult patient who developed malignant fibrous histiocytoma 9 years after radiation therapy for childhood acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Yasuhiro [National Hiroshima Hospital, Higashi-Hiroshima (Japan); Ohno, Norioki; Horikawa, Yoko; Nishimura, Shin-ichiro; Ueda, Kazuhiro; Shimose, Shoji [Hiroshima Univ. (Japan). School of Medicine

    2002-12-01

    A 24-year-old Japanese man with a history of acute lymphoblastic leukemia, which occurred during childhood, developed malignant fibrous histiocytoma of his left knee. His past history revealed that he had undergone leukemic blast cell invasion of the left knee and subsequent radiation therapy 9 years ago. The total radiation doses for the upper part of the left tibia and the lower part of the left femur were 60 Gy and 40 Gy, respectively. Neither distant metastasis nor a relapse of leukemia occurred. A curative resection of the left femur with a noninvasive margin was performed. Adjuvant chemotherapy including high-dose methotrexate was given successfully before and after surgery; this was followed by relapse-free survival for 3 years. The nature of postirradiation malignant fibrous histiocytoma is highly aggressive. When a patient complains of persistent symptoms in a previously irradiated field, the possibility of this tumor must be taken into account. The importance of early diagnosis cannot be over-emphasized. (author)

  5. Mapping of murine radiation-induced acute myeloid leukaemia susceptibility loci

    Energy Technology Data Exchange (ETDEWEB)

    Darakhshan, F

    2001-01-01

    Studies on radiation-induced AML have shown characteristic phenotypic variation in susceptibility amongst inbred mouse strains, suggesting the involvement of genetic factors in determining the development of AML post-irradiation exposure. The main objective of the present study therefore was to identify and map markers in linkage disequilibrium with gene variants associated with influencing susceptibility to radiation induced AML in mice. Given Chr 2 abnormalities are characteristic of AML in mice, this feature was exploited in an effort to overcome the long latency for AML development. Analysis of Chr 2 aberrations at 24 and 48 h following irradiation established a positive correlation between Chr 2 radiosensitivity and radiation-AML susceptibility thus validating the choice of substitute assay. The analysis also resulted in the identification of a further trait, additional to Chr 2 radiosensitivity, termed overall chromosome radiosensitivity. Genetic mapping of Chr 2 radiosensitivity using public domain microsatellite database information resulted in the definition of cluster regions on 7 different chromosomes. Further genotyping reduced the candidate regions to 3 specific regions of interest. A test of allelic association could not ascertain a conclusive link between markers at these regions and the Chr 2 radiosensitivity/radiation-AML susceptibility phenotype. However, a region on Chr 4 around D4Mit221 appears to be most strongly associated. Similar studies identified three chromosomal regions of interest (on Chrs 4, 8 and 16) associated with overall chromosome radiosensitivity trait. An independent mapping strategy using F3 RCS confirmed the likely involvement of two of the candidate Chr 2 radiosensitivity regions identified by the inbred analysis including that on Chr 4 and also highlighted phenotypic heterogeneity amongst resistant RC strains, suggesting the influence of multiple alleles in specific phenotypes. RFLP analysis of candidate genes, localised on

  6. A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures

    Science.gov (United States)

    2016-08-01

    Act of 1979, as amended, Title 50, U.S.C., App. 2401 et seq. Violations of these export laws are subject to severe criminal penalties ...DTRA-TR-16-059 DISTRIBUTION A. Approved for public release: distribution is unlimited. Exposure to burn and radiation elicit epithelial cell death in...villus cells, promoting early cell death before migration is complete (Carter et al., 2014, Wolf et al., 1999). This response is fast and strong but

  7. Phase I study of celecoxib with concurrent irinotecan, cisplatin, and radiation therapy for patients with unresectable locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ritsuko eKomaki

    2011-12-01

    Full Text Available Purpose: Preclinical findings suggest that adding targeted therapies to combination radiation-chemotherapy can enhance treatment efficacy; however, this approach may enhance normal tissue toxicity. We investigated the maximum tolerated dose, dose-limiting toxicities, and response rate when the selective cyclo-oxygenase-2 inhibitor celecoxib is added to concurrent irinotecan, cisplatin, and radiation therapy for patients with inoperable stage II-III non-small cell lung cancer. Methods and materials: Eighteen patients were analyzed in a phase I clinical dose-escalation trial. Celecoxib was given daily beginning 5 days before radiation followed by maintenance doses for 12 weeks. Toxicity was graded with the Common Terminology Criteria for Adverse Events V3.0 and response with the World Health Organization system. Primary endpoints were maximum tolerated dose of celecoxib and treatment toxicity; secondary endpoints were response and survival rates. Results: The maximum tolerated dose of celecoxib was not reached, in part owing to discontinuation of the drug supply. At doses of 200 or 400 mg/day, no patients experienced any dose-limiting toxicity (acute grade ≥4 esophagitis or pneumonitis, neutropenic fever or thrombocytopenia requiring transfusion, or acute grade ≥3 diarrhea. Grade 3 toxicities were leukopenia (5 patients, fatigue (3, pneumonitis (2, dyspnea (1, pain (1, and esophageal stricture (1. Interestingly, pulmonary fibrosis (a late toxicity was no more severe in the higher-dose (400-mg group and may have been less common than in the lower-dose group. The clinical response rate was 100% (8 complete, 10 partial. Two-year rates were: overall survival 65%; local-regional control 69%; distant metastasis-free survival 71%; and disease-free survival 64%. Conclusions: Although preliminary, our results suggest that adding celecoxib to concurrent chemoradiation for inoperable NSCLC is safe and can improve outcome without increasing normal tissue

  8. Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to Total Body Irradiation.

    Science.gov (United States)

    Unthank, Joseph L; Miller, Steven J; Quickery, Ariel K; Ferguson, Ethan L; Wang, Meijing; Sampson, Carol H; Chua, Hui Lin; DiStasi, Matthew R; Feng, Hailin; Fisher, Alexa; Katz, Barry P; Plett, P Artur; Sandusky, George E; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P; MacVittie, Thomas J; Orschell, Christie M

    2015-11-01

    The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.

  9. Response to and recovery from acute sublethal gamma radiation in the Amazon molly, Poecilia formosa

    Energy Technology Data Exchange (ETDEWEB)

    Woodhead, A.D.; Setlow, R.B.

    1979-05-01

    Acute irradiation of the Amazon molly with a sublethal dose of 1,000 rad caused some damage to the intestinal tract and to the haematopoietic system. Histologically, the intestine appeared to have regenerated by the end of a week; damage to the haematopoietic tissue appeared more slowly, but repair was almost complete some two months later. Nevertheless, recovery to the intestine cannot have been entirely completed in seven days, since the fish did not feed well for the following two weeks. After this, there were no obvious deleterious effects upon the survival and viability of the fish, although irradiated fish weighed less at the termination of the experiment.

  10. Characterization of systemic and pneumonic murine models of plague infection using a conditionally virulent strain.

    Science.gov (United States)

    Mellado-Sanchez, Gabriela; Ramirez, Karina; Drachenberg, Cinthia B; Diaz-McNair, Jovita; Rodriguez, Ana L; Galen, James E; Nataro, James P; Pasetti, Marcela F

    2013-03-01

    Yersinia pestis causes bubonic and pneumonic plague in humans. The pneumonic infection is the most severe and invariably fatal if untreated. Because of its high virulence, ease of delivery and precedent of use in warfare, Y. pestis is considered as a potential bioterror agent. No licensed plague vaccine is currently available in the US. Laboratory research with virulent strains requires appropriate biocontainment (i.e., Biosafety Level 3 (BSL-3) for procedures that generate aerosol/droplets) and secure facilities that comply with federal select agent regulations. To assist in the identification of promising vaccine candidates during the early phases of development, we characterized mouse models of systemic and pneumonic plague infection using the Y. pestis strain EV76, an attenuated human vaccine strain that can be rendered virulent in mice under in vivo iron supplementation. Mice inoculated intranasally or intravenously with Y. pestis EV76 in the presence of iron developed a systemic and pneumonic plague infection that resulted in disease and lethality. Bacteria replicated and severely compromised the spleen, liver and lungs. Susceptibility was age dependent, with younger mice being more vulnerable to pneumonic infection. We used these models of infection to assess the protective capacity of newly developed Salmonella-based plague vaccines. The protective outcome varied depending on the route and dose of infection. Protection was associated with the induction of specific immunological effectors in systemic/mucosal compartments. The models of infection described could serve as safe and practical tools for identifying promising vaccine candidates that warrant further potency evaluation using fully virulent strains in BSL-3 settings. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Deficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Leung, Wing; Neale, Geoffrey; Behm, Fred; Iyengar, Rekha; Finkelstein, David; Kastan, Michael B; Pui, Ching-Hon

    2010-06-01

    Survivors of childhood acute lymphoblastic leukemia (ALL) are at an increased risk of developing secondary malignant neoplasms. Radiation and chemotherapy can cause mutations and cytogenetic abnormalities and induce genomic instability. Host immunity and appropriate DNA damage responses are critical inhibitors of carcinogenesis. Therefore, we sought to determine the long-term effects of ALL treatment on immune function and response to DNA damage. Comparative studies on 14 survivors in first complete remission and 16 siblings were conducted. In comparison to siblings on the cells that were involved in adaptive immunity, the patients had either higher numbers (CD19+ B cells and CD4+CD25+ T regulatory cells) or similar numbers (alphabetaT cells and CD45RO+/RA- memory T cells) in the blood. In contrast, patients had lower numbers of all lymphocyte subsets involved in innate immunity (gammadeltaT cells and all NK subsets, including KIR2DL1+ cells, KIR2DL2/L3+ cells, and CD16+ cells), and lower natural cytotoxicity against K562 leukemia cells. Thymopoiesis was lower in patients, as demonstrated by less CD45RO-/RA+ naïve T cell and less SjTREC levels in the blood, whereas the Vbeta spectratype complexity score was similar. Array of gene expression response to low-dose radiation showed that about 70% of the probesets had a reduced response in patients. One of these genes, SCHIP-1, was also among the top-ranked single nucleotide polymorphisms (SNPs) during the whole-genome scanning by SNP microarray analysis. ALL survivors were deficient in innate immunity, thymopoiesis, and DNA damage responses to radiation. These defects may contribute to their increased likelihood of second malignancy. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  12. Ultrasonic analysis of acute thermal and radiation injury - A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Goans, R.E. [MJW Corporation, Amherst, NY 14228 (United States); Tulane School of Public Health and Tropical Medicine, New Orleans, LA 70112 (United States)], E-mail: ronald.goans@comcast.net; Goans, R.H. [Department of Mathematics, University of Tennessee, Knoxville, TN 37996 (United States); Goans, R.E. [Department of Physics, University of Tennessee, Knoxville, TN 37996 (United States); Christensen, D.M. [Radiation Emergency Assistance Center/Training Site (REAC/TS), Oak Ridge, TN 37830 (United States)

    2007-07-15

    Medical injury from a terrorist event (IND, RDD) is likely to involve both radiation damage and thermal trauma (combined injury). A high-frequency ultrasound technique has previously been developed to function as a clinical tool to distinguish partial-thickness from full-thickness thermal burns in a porcine model and the method was later extended for use in clinical burn units. In a traditional clinical setting, the technique has shown sufficient sensitivity to quantitate extension of a partial-thickness burn to a full-thickness burn through cutaneous infection. The ultrasound method has been extended in a pilot study to analyze radiation-induced cutaneous injury. Analysis of radiation-induced skin injury is more difficult than for thermal injury. However, further development of the method has shown a time-dependent response curve for the scattered ultrasound signal after irradiation of Wistar rat tails to 40 Gy with a 120 KeV X-ray spectrum. Statistically significant changes (p<0.05) in the magnitude of the reflected ultrasound spectrum have been noted less than 6 h-post-irradiation. The scattered intensity response curve peaks near the appearance of the first clinical sign (erythema) at 12 days post-irradiation. The mechanism of ultrasound sensitivity appears to involve changes in the tissue acoustic impedance post-irradiation possibly due to hyperemia, vascular damage and leakage. Because of the penetrating power and resolution of recent ultrasound equipment, this technique is expected to be extendable to analysis of irradiated deep organs, of large- and medium-size blood vessels, and to possible analysis of combined injury.

  13. Study on radioprotection effects of clinoptilolite on sub-acute radiation-injured mice

    Directory of Open Access Journals (Sweden)

    Na LI

    2016-03-01

    Full Text Available Objective  To study the protection effect of clinoptilolite (Cp against radiation injury. Methods  Fortyeight male BALB/c mice were randomly divided into 6 groups, namely normal control group (distilled water + sham irradiation, radiation control group (distilled water + irradiation, 300mg/kg 523 group (200mg/kg nilestriol 24h before irradiation and 100mg/ kg nilestriol 4h after irradiation, 56mg/kg Cp group (56mg/kg Cp + irradiation, 167mg/kg Cp group (167mg/kg Cp + irradiation and 500mg/kg Cp group (500mg/kg Cp + irradiation. Seven days after the administration of the drug, all the mice but those from the normal control group were irradiated with γ-ray irradiation of 137Cs in the dose of 4.0Gy, at the rate of 0.75Gy/min. All the mice were given the drug for 14 days after irradiation. RBC, WBC and PLT counts in peripheral blood, superoxide dismutases (SOD activity, malondialdehyde (MDA level, glutathione peroxidase (GSH-Px level in blood serum, the content of deoxyribonucleic acid (DNA and hematopoietic stem cells in bone marrow were determined. Results  Compared with radiation control group, on 10th day after irradiation, RBC counts in peripheral blood of 56mg/kg Cp group and 167mg/kg Cp group were significantly higher (P<0.05, P<0.01, and WBC counts in peripheral blood of 56mg/kg Cp group and 500mg/kg Cp group were significantly higher (P<0.01. On 14th day after irradiation, compared with radiation control group, the SOD activities in blood serum of three Cp groups were elevated (P<0.05, P<0.01, the GSH-Px levels were elevated in blood serum of 167mg/kg Cp group and 500mg/kg Cp group (P<0.01, the DNA contents were significantly higher in 56mg/kg Cp group and 500mg/kg Cp group (P<0.05, P<0.01, the hematopoietic stem cells were significantly increased in number in bone marrow of three Cp groups (P<0.01. Conclusion  The clinoptilolite possesses protective effect against injury induced by 137Cs γ-irradiation in mice. DOI: 10.11855/j

  14. Acute Ultraviolet Radiation Perturbs Epithelialization but not the Biomechanical Strength of Full-thickness Cutaneous Wounds

    DEFF Research Database (Denmark)

    Danielsen, Patricia L; Lerche, Catharina M; Wulf, Hans Christian;

    2016-01-01

    We hypothesized that priming of the skin with ultraviolet radiation (UVR) before being injured would enhance wound healing. Four groups, each comprising 20 immunocompetent hairless mice, were exposed to simulated solar irradiation in escalating UVR doses; 0 standard erythema dose (SED) = control, 1...... (P exposure of dorsal skin. In the excisional wounds, epithelial coverage decreased (P = 0.024) by increasing the UVR dose, whereas there was no significant difference (P = 0.765) in wound MPO levels. Neither wound width (P = 0.850) nor breaking strength (P...

  15. Acute radiation effects on cutaneous microvasculature: evaluation with a laser Doppler perfusion monitor

    Energy Technology Data Exchange (ETDEWEB)

    Amols, H.I.; Goffman, T.E.; Komaki, R.; Cox, J.D.

    1988-11-01

    Laser Doppler perfusion monitoring is a noninvasive technique for measuring blood flow in epidermal microvasculature that makes use of the frequency shift of light reflected from red blood cells. Measurements in patients undergoing radiation therapy show increases in blood flow of ten to 25 times baseline at doses above 50 Gy, and increases are observed with doses as low as 2 Gy. Follow-up measurements show rapid decreases in flow levels after completion of therapy, but levels remain elevated even at 1 year.

  16. Successful Pregnancy and Delivery After Radiation With Ovarian Shielding for Acute Lymphocytic Leukemia Before Menarche.

    Science.gov (United States)

    Ishibashi, Naoya; Maebayashi, Toshiya; Aizawa, Takuya; Sakaguchi, Masakuni; Abe, Osamu; Saito, Tsutomu; Tanaka, Yoshiaki; Chin, Motoaki; Mugishima, Hideo

    2015-07-01

    Total body irradiation is performed as a preconditioning regimen to inhibit graft-versus-host disease after bone marrow transplantation and to eradicate remaining tumor cells. However, these regimens result in delayed secondary sex characteristics and failure of ovarian function recovery, leading to amenorrhea and infertility. Herein, we report a case of an 11-year-old girl diagnosed with acute lymphocytic leukemia who received induction chemotherapy and prophylactic cranial irradiation. For bone marrow transplantation, she received total body irradiation of 12 Gy with uterine and ovarian shielding at 13 years of age. The patient remained in remission and menarche began at 14 years of age. At 23, she became pregnant and delivered a baby naturally with no abnormalities.

  17. A case of lung cancer associated with acute respiratory distress syndrome after thoracic radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Enoki, Masafumi; Tojima, Hirokazu [Tokyo Rosai Hospital (Japan)

    1996-12-01

    A 73-year-old man presented with dyspnea, cough, fever, appetite loss and stridor due to bronchial stenosis. Fiber-optic bronchoscopy revealed an endobronchial lesion in the right main bronchus and biopsy specimens showed poorly differentiated squamous cell carcinoma. The clinical stage of lung cancer was IIIB (T4N2M0). The patient received 60 Gy in 30 fractions over 43 days to a field including the right hilum and mediastinum. The tumor decreased in size and stenosis of the bronchus disappeared. A week after completion of radiation the patient began to have high grade fever and dyspnea, and progressive hypoxia developed. A chest radiograph showed diffuse bilateral interstitial infiltrates. Despite mechanical ventilation with PEEP and the administration of steroids, he died of respiratory failure three weeks after completion of radiation. Necropsy specimens obtained from the left lung revealed massive deposition of fibrin in the alveolar airspaces associated with hyaline membranes and hyperplasia of type II cells indicating diffuse alveolar damage. The patient had mild pulmonary fibrosis on a CT scan taken before the start of radiotherapy. We conclude that care should be taken if the case has pulmonary fibrosis because radiation therapy can precipitate severe radiation pneumonitis and acute respiratory distress syndrome in such cases. (author)

  18. Effects of radiation dose reduction in Volume Perfusion CT imaging of acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Othman, Ahmed E. [RWTH Aachen University, Department of Diagnostic and Interventional Neuroradiology, Aachen (Germany); Eberhard Karls University Tuebingen, University Hospital Tuebingen, Department for Diagnostic and Interventional Radiology, Tuebingen (Germany); Brockmann, Carolin; Afat, Saif; Pjontek, Rastislav; Nikobashman, Omid; Brockmann, Marc A.; Wiesmann, Martin [RWTH Aachen University, Department of Diagnostic and Interventional Neuroradiology, Aachen (Germany); Yang, Zepa; Kim, Changwon [Seoul National University, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Suwon (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Kim, Jong Hyo [Seoul National University, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Suwon (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Center for Medical-IT Convergence Technology Research, Advanced Institute of Convergence Technology, Suwon (Korea, Republic of)

    2015-12-15

    To examine the influence of radiation dose reduction on image quality and sensitivity of Volume Perfusion CT (VPCT) maps regarding the detection of ischemic brain lesions. VPCT data of 20 patients with suspected ischemic stroke acquired at 80 kV and 180 mAs were included. Using realistic reduced-dose simulation, low-dose VPCT datasets with 144 mAs, 108 mAs, 72 mAs and 36 mAs (80 %, 60 %, 40 % and 20 % of the original levels) were generated, resulting in a total of 100 datasets. Perfusion maps were created and signal-to-noise-ratio (SNR) measurements were performed. Qualitative analyses were conducted by two blinded readers, who also assessed the presence/absence of ischemic lesions and scored CBV and CBF maps using a modified ASPECTS-score. SNR of all low-dose datasets were significantly lower than those of the original datasets (p <.05). All datasets down to 72 mAs (40 %) yielded sufficient image quality and high sensitivity with excellent inter-observer-agreements, whereas 36 mAs datasets (20 %) yielded poor image quality in 15 % of the cases with lower sensitivity and inter-observer-agreements. Low-dose VPCT using decreased tube currents down to 72 mAs (40 % of original radiation dose) produces sufficient perfusion maps for the detection of ischemic brain lesions. (orig.)

  19. Acute skin lesions following psoralen plus ultraviolet A radiation investigated by optical coherence tomography

    Science.gov (United States)

    Liu, Z. M.; Zhong, H. Q.; Zhai, J.; Wang, C. X.; Xiong, H. L.; Guo, Z. Y.

    2013-08-01

    Psoralen plus ultraviolet A radiation (PUVA) therapy is a very important clinical treatment of skin diseases such as vitiligo and psoriasis, but associated with an increased risk of skin photodamage, especially photoaging. In this work, optical coherence tomography (OCT), a novel non-invasive imaging technology, was introduced to investigate in vivo the photodamage induced by PUVA qualitatively and quantitatively. Balb/c mouse dorsal skin was treated with 8-methoxypsoralen (8-MOP), and then exposed to UVA radiation. OCT images of the tissues were obtained by an OCT system with a 1310 nm central wavelength. Skin thickness and the attenuation coefficient were extracted from the OCT images to analyze the degree of injury to mouse skin. The results demonstrated that PUVA-treated skin showed an increase in skin thickness, and a reduction of attenuation coefficient in the OCT signal compared with the control groups. The data also showed good correlation with the results observed in histological sections using hematoxylin and eosin staining. In conclusion, OCT is a promising tool for photobiological studies aimed at assessing the effect of PUVA therapy in vivo.

  20. A new CT-based method to quantify radiation-induced lung damage in patients.

    Science.gov (United States)

    Ghobadi, Ghazaleh; Wiegman, Erwin M; Langendijk, Johannes A; Widder, Joachim; Coppes, Robert P; van Luijk, Peter

    2015-10-01

    A new method to assess radiation-induced lung toxicity (RILT) using CT-scans was developed. It is more sensitive in detecting damage and corresponds better to physician-rated radiation pneumonitis than routinely-used methods. Use of this method may improve lung toxicity assessment and thereby facilitate development of more accurate predictive models for RILT.

  1. Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients.

    Science.gov (United States)

    Franco, Pierfrancesco; Rampino, Monica; Ostellino, Oliviero; Schena, Marina; Pecorari, Giancarlo; Garzino Demo, Paolo; Fasolis, Massimo; Arcadipane, Francesca; Martini, Stefania; Cavallin, Chiara; Airoldi, Mario; Ricardi, Umberto

    2017-02-01

    Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.

  2. Comparison of Acute and Late Toxicities for Three Modern High-Dose Radiation Treatment Techniques for Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mohammed, Nasiruddin [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Kestin, Larry, E-mail: lkestin@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Ghilezan, Mihai; Krauss, Daniel; Vicini, Frank; Brabbins, Donald; Gustafson, Gary; Ye Hong; Martinez, Alavaro [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)

    2012-01-01

    Purpose: We compared acute and late genitourinary (GU) and gastrointestinal (GI) toxicities in prostate cancer patients treated with three different high-dose radiation techniques. Methods and Materials: A total of 1,903 patients with localized prostate cancer were treated with definitive RT at William Beaumont Hospital from 1992 to 2006: 22% with brachytherapy alone (BT), 55% with image-guided external beam (EB-IGRT), and 23% external beam with high-dose-rate brachytherapy boost (EBRT+HDR). Median dose with BT was 120 Gy for LDR and 38 Gy for HDR (9.5 Gy Multiplication-Sign 4). Median dose with EB-IGRT was 75.6 Gy (PTV) to prostate with or without seminal vesicles. For EBRT+HDR, the pelvis was treated to 46 Gy with an additional 19 Gy (9.5 Gy Multiplication-Sign 2) delivered via HDR. GI and GU toxicity was evaluated utilizing the NCI-CTC criteria (v.3.0). Median follow-up was 4.8 years. Results: The incidences of any acute {>=} Grade 2 GI or GU toxicities were 35%, 49%, and 55% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Any late GU toxicities {>=} Grade 2 were present in 22%, 21%, and 28% for BT, EB-IGRT, and EBRT+HDR (p = 0.01), respectively. Patients receiving EBRT+HDR had a higher incidence of urethral stricture and retention, whereas dysuria was most common in patients receiving BT. Any Grade {>=}2 late GI toxicities were 2%, 20%, and 9% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Differences were most pronounced for rectal bleeding, with 3-year rates of 0.9%, 20%, and 6% (p < 0.001) for BT, EB-IGRT, and EBRT+HDR respectively. Conclusions: Each of the three modern high-dose radiation techniques for localized prostate cancer offers a different toxicity profile. These data can help patients and physicians to make informed decisions regarding radiotherapy for prostate andenocarcinoma.

  3. Statistical Prediction of Solar Particle Event Frequency Based on the Measurements of Recent Solar Cycles for Acute Radiation Risk Analysis

    Science.gov (United States)

    Myung-Hee, Y. Kim; Shaowen, Hu; Cucinotta, Francis A.

    2009-01-01

    Large solar particle events (SPEs) present significant acute radiation risks to the crew members during extra-vehicular activities (EVAs) or in lightly shielded space vehicles for space missions beyond the protection of the Earth's magnetic field. Acute radiation sickness (ARS) can impair performance and result in failure of the mission. Improved forecasting capability and/or early-warning systems and proper shielding solutions are required to stay within NASA's short-term dose limits. Exactly how to make use of observations of SPEs for predicting occurrence and size is a great challenge, because SPE occurrences themselves are random in nature even though the expected frequency of SPEs is strongly influenced by the time position within the solar activity cycle. Therefore, we developed a probabilistic model approach, where a cumulative expected occurrence curve of SPEs for a typical solar cycle was formed from a non-homogeneous Poisson process model fitted to a database of proton fluence measurements of SPEs that occurred during the past 5 solar cycles (19 - 23) and those of large SPEs identified from impulsive nitrate enhancements in polar ice. From the fitted model, the expected frequency of SPEs was estimated at any given proton fluence threshold (Phi(sub E)) with energy (E) >30 MeV during a defined space mission period. Corresponding Phi(sub E) (E=30, 60, and 100 MeV) fluence distributions were simulated with a random draw from a gamma distribution, and applied for SPE ARS risk analysis for a specific mission period. It has been found that the accurate prediction of deep-seated organ doses was more precisely predicted at high energies, Phi(sub 100), than at lower energies such as Phi(sub 30) or Phi(sub 60), because of the high penetration depth of high energy protons. Estimates of ARS are then described for 90th and 95th percentile events for several mission lengths and for several likely organ dose-rates. The ability to accurately measure high energy protons

  4. Occurrence of HSV-1-induced pneumonitis in patients under standard immunosuppressive therapy for rheumatic, vasculitic, and connective tissue disease

    Directory of Open Access Journals (Sweden)

    Ihrler Stephan

    2009-05-01

    Full Text Available Abstract Background Herpes simplex virus type-1 (HSV-1 has been described to cause respiratory tract infections in critically ill patients or in individuals that are immunocompromised. It is a continuing matter of debate under which circumstances HSV-1 is a relevant pathogen for pneumonitis. While its role during critical illness has been investigated by prospective interventional studies, comparatively little systematic data is available on the role of HSV-1 for pneumonitis in outpatients with autoimmune disease under a maintenance regimen of immunosuppression. Methods We retrospectively reviewed the charts of ~1400 patients with rheumatoid arthritis, vasculitis, and systemic lupus erythematosus (SLE that were followed at the outpatient clinic of a German University hospital during the years 2000–2007. Episodes of admission to a ward resulting in the diagnosis of pneumonia/pneumonitis were identified, and the type of pneumonia and clinical features retrospectively studied. Results 63 patients with rheumatoid arthritis, vasculitis, or SLE were admitted to a ward and diagnosed to have pneumonia/pneumonitis. Using bronchoscopy a total of 6 cases of pulmonary infection associated with HSV-1 in the lower respiratory tract were identified. Among those, 2 cases suggested a causative role of HSV-1 as the sole agent causing pneumonitis that proved clinically responsive to antiviral treatment. In the remaining 4 cases HSV-1 appeared as a bystander of bacterial infection. Maintenance therapy with leflunomide, which inhibits HSV-1 assembly in vitro, was associated with a milder course of pneumonitis in one patient. Detection of HSV-1 was associated with stronger immunosuppressive regimens and vasculitic disease. Conclusion The present study analyzed the frequency and hallmarks of cases of HSV-1 associated pneumonitis that occurred in a comparatively large cohort of patients with rheumatologic autoimmune diseases. In an area of controversy, this study

  5. Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jiayi, E-mail: jhuang@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); DeWees, Todd A.; Badiyan, Shahed N.; Speirs, Christina K.; Mullen, Daniel F.; Fergus, Sandra [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); Tran, David D.; Linette, Gerry; Campian, Jian L. [Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri (United States); Chicoine, Michael R.; Kim, Albert H.; Dunn, Gavin [Department of Neurosurgery, Washington University School of Medicine, St Louis, Missouri (United States); Simpson, Joseph R.; Robinson, Clifford G. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States)

    2015-08-01

    Purpose: Acute severe lymphopenia (ASL) frequently develops during radiation therapy (RT) and concurrent temozolomide (TMZ) for high-grade glioma (HGG) and is associated with decreased survival. The current study was designed to identify potential predictors of ASL, with a focus on actionable RT-specific dosimetric parameters. Methods and Materials: From January 2007 to December 2012, 183 patients with HGG were treated with RT+TMZ and had available data including total lymphocyte count (TLC) and radiation dose-volume histogram parameters. ASL was defined as TLC of <500/μL within the first 3 months from the start of RT. Stepwise logistic regression analysis was used to determine the most important predictors of ASL. Results: Fifty-three patients (29%) developed ASL. Patients with ASL had significantly worse overall survival than those without (median: 12.5 vs 20.2 months, respectively, P<.001). Stepwise logistic regression analysis identified female sex (odds ratio [OR]: 5.30; 95% confidence interval [CI]: 2.46-11.41), older age (OR: 1.05; 95% CI: 1.02-1.09), lower baseline TLC (OR: 0.92; 95% CI: 0.87-0.98), and higher brain volume receiving 25 Gy (V{sub 25Gy}) (OR: 1.03; 95% CI: 1.003-1.05) as the most significant predictors for ASL. Brain V{sub 25Gy} <56% appeared to be the optimal threshold (OR: 2.36; 95% CI: 1.11-5.01), with an ASL rate of 38% versus 20% above and below this threshold, respectively (P=.006). Conclusions: Female sex, older age, lower baseline TLC, and higher brain V{sub 25Gy} are significant predictors of ASL during RT+TMZ therapy for HGG. Maintaining the V{sub 25Gy} of brain below 56% may reduce the risk of ASL.

  6. Influence of Double-Strand Break Repair on Radiation Therapy-Induced Acute Skin Reactions in Breast Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Mumbrekar, Kamalesh Dattaram [Division of Radiobiology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka (India); Fernandes, Donald Jerard [Department of Radiotherapy and Oncology, Shirdi Sai Baba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka (India); Goutham, Hassan Venkatesh [Division of Radiobiology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka (India); Sharan, Krishna [Department of Radiotherapy and Oncology, Shirdi Sai Baba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka (India); Vadhiraja, Bejadi Manjunath [Manipal Hospital, Bangalore, Karnataka (India); Satyamoorthy, Kapaettu [Division of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka (India); Bola Sadashiva, Satish Rao, E-mail: satishraomlsc@gmail.com [Division of Radiobiology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka (India)

    2014-03-01

    Purpose: Curative radiation therapy (RT)-induced toxicity poses strong limitations for efficient RT and worsens the quality of life. The parameter that explains when and to what extent normal tissue toxicity in RT evolves would be of clinical relevance because of its predictive value and may provide an opportunity for personalized treatment approach. Methods and Materials: DNA double-strand breaks and repair were analyzed by microscopic γ-H2AX foci analysis in peripheral lymphocytes from 38 healthy donors and 80 breast cancer patients before RT, a 2 Gy challenge dose of x-ray exposed in vitro. Results: The actual damage (AD) at 0.25, 3, and 6 hours and percentage residual damage (PRD) at 3 and 6 hours were used as parameters to measure cellular radiosensitivity and correlated with RT-induced acute skin reactions in patients stratified as non-overresponders (NOR) (Radiation Therapy Oncology Group [RTOG] grade <2) and overresponders (OR) (RTOG grade ≥2). The results indicated that the basal and induced (at 0.25 and 3 hours) γ-H2AX foci numbers were nonsignificant (P>.05) between healthy control donors and the NOR and OR groups, whereas it was significant between ORs and healthy donors at 6 hours (P<.001). There was a significantly higher PRD in OR versus NOR (P<.05), OR versus healthy donors (P<.001) and NOR versus healthy donors (P<.01), supported further by the trend analysis (r=.2392; P=.0326 at 6 hours). Conclusions: Our findings strongly suggest that the measurement of PRD by performing γ-H2AX foci analysis has the potential to be developed into a clinically useful predictive assay.

  7. C-reactive protein and serum amyloid A as early-phase and prognostic indicators of acute radiation exposure in nonhuman primate total-body irradiation model

    Energy Technology Data Exchange (ETDEWEB)

    Ossetrova, N.I., E-mail: ossetrova@afrri.usuhs.mil [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bldg. 42, Bethesda, MD 20889-5603 (United States); Sandgren, D.J.; Blakely, W.F. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bldg. 42, Bethesda, MD 20889-5603 (United States)

    2011-09-15

    Terrorist radiological attacks or nuclear accidents could expose large numbers of people to ionizing radiation. In mass-casualty radiological incidents early medical-management requires triage tools for first-responders to quantitatively identify individuals exposed to life-threatening radiation doses and for early initiation (i.e., within one day after radiation exposure) of cytokine therapy for treatment of bone marrow acute radiation syndrome. Herein, we present results from 30 rhesus macaques total-body irradiated (TBI) to a broad dose range of 1-8.5 Gy with {sup 60}Co {gamma}-rays (0.55 Gy min{sup -1}) and demonstrate dose- and time-dependent changes in blood of C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) measured by enzyme linked immunosorbent assay (ELISA). CRP and SAA dose-response results are consistent with {approx}1 Gy and {approx}0.2 Gy thresholds for photon-exposure at 24 h after TBI, respectively. Highly significant elevations of CRP and SAA (p = 0.00017 and p = 0.0024, respectively) were found in animal plasma at 6 h after all TBI doses suggesting their potential use as early-phase biodosimeters. Results also show that the dynamics and content of CRP and SAA levels reflect the course and severity of the acute radiation sickness (ARS) and may function as prognostic indicators of ARS outcome. These results demonstrate proof-of-concept that these radiation-responsive proteins show promise as a complementary approach to conventional biodosimetry for early assessment of radiation exposures and may also contribute as diagnostic indices in the medical management of radiation accidents.

  8. Use of the adaptive classifier for determination of LD50 in the acute radiation disease.

    Science.gov (United States)

    Vodicka, I; Hanus, J; Hradil, J

    1989-01-01

    In experiments on female Wistar rats a new method for the determination of LD50 is demonstrated and compared with the classical probit method using the same experimental animals. The method is applicable for the computation of LD50 and analogical quantities in man, too. The method is based on the application of an adaptive logical circuit (ADALINE) trained for the dichotomous prognostic classification of irradiated individuals quod vitam according to a set of clinical and laboratory indicators registered on the third day after irradiation. After the training procedure has been finished, the classifier makes possible an individual prognosis of survival or death. The analogue output signal according to which the classification is performed changes continually from negative to positive values and exhibits S-shaped relation to the radiation dose. Its zero value corresponds to the position of LD50 on the abscissa. For the construction of the searched function, i.e. for the optimum approximation of experimentally obtained values of the output signal, the method of the changeable polyhedron was applied belonging to the optimalization numerical methods used in the regulation technics. The computed value of LD50 was 7.80 Gy in rats very closely corresponding with the value 7.61 Gy determined by means of the classical probit method.

  9. Prevention of bubonic and pneumonic plague using plant-derived vaccines.

    Science.gov (United States)

    Alvarez, M Lucrecia; Cardineau, Guy A

    2010-01-01

    Yersinia pestis, the causative agent of bubonic and pneumonic plague, is an extremely virulent bacterium but there are currently no approved vaccines for protection against this organism. Plants represent an economical and safer alternative to fermentation-based expression systems for the production of therapeutic proteins. The recombinant plague vaccine candidates produced in plants are based on the two most immunogenic antigens of Y. pestis: the fraction-1 capsular antigen (F1) and the low calcium response virulent antigen (V) either in combination or as a fusion protein (F1-V). These antigens have been expressed in plants using all three known possible strategies: nuclear transformation, chloroplast transformation and plant-virus-based expression vectors. These plant-derived plague vaccine candidates were successfully tested in animal models using parenteral, oral, or prime/boost immunization regimens. This review focuses on the recent research accomplishments towards the development of safe and effective pneumonic and bubonic plague vaccines using plants as bioreactors.

  10. Hypersensitivity Pneumonitis in a Housewife Exposed to Aspergillus flavus in Poor Living Conditions: A Case Report

    Science.gov (United States)

    Estibeiro, Anita Sandhya Mendonca; Mesquita, Anthony Menezes

    2016-01-01

    Hypersensitivity Pneumonitis (HP) or Extrinsic Allergic Alveolitis (EAA) is a disease resulting from immunologically induced inflammation in response to inhalation of a wide variety of airborne allergens. The condition develops mainly in non atopic individuals sensitized to organic dust due to repeated exposures. It is a relatively rare disease constituting upto 2% of interstitial lung diseases. Knowledge of classical High Resolution Computed Tomography (HRCT) of lung findings aid in early diagnosis. We report a case of subacute hypersensitivity pneumonitis in a housewife who despite being symptomatic remained undiagnosed for two years. She showed a good response to therapy, but soon relapsed. Visit to her home revealed that she lived in a damp house full of moldy walls. PMID:26894116

  11. Early host cell targets of Yersinia pestis during primary pneumonic plague.

    Directory of Open Access Journals (Sweden)

    Roger D Pechous

    Full Text Available Inhalation of Yersinia pestis causes primary pneumonic plague, a highly lethal syndrome with mortality rates approaching 100%. Pneumonic plague progression is biphasic, with an initial pre-inflammatory phase facilitating bacterial growth in the absence of host inflammation, followed by a pro-inflammatory phase marked by extensive neutrophil influx, an inflammatory cytokine storm, and severe tissue destruction. Using a FRET-based probe to quantitate injection of effector proteins by the Y. pestis type III secretion system, we show that these bacteria target alveolar macrophages early during infection of mice, followed by a switch in host cell preference to neutrophils. We also demonstrate that neutrophil influx is unable to limit bacterial growth in the lung and is ultimately responsible for the severe inflammation during the lethal pro-inflammatory phase.

  12. Psychophysiological adaptation of the patient with the remote effect of the III degree acute radiation syndrome

    Directory of Open Access Journals (Sweden)

    Metlyaeva N.A.

    2013-12-01

    putation of both shins at level in top / 3, late beam buttock, right hip ulcers, a beam cataract of the III degree of both eyes, stabilized. The assessment of the efficiency of psychophysiological adaptation in dynamics with 2009 indicates emergence of prevalence of hypochondriac tendencies over a demonstration with accession of high uneasiness and autistic lines at preservation of the leading role of an hypochondriac somatization of alarm with considerable decrease in an emotionality, an integration, a freedom of behavior. The changes revealed in dynamics correspond to the specific increase weight of violations of mental adaptation, characteristic for the period of adaptation exhaustion. The high intelligence, good figurative and logical thinking, well-mannered forms of behavior, high control over the emotional sphere, restraint of emotions, independence, self-sufficiency, organization, behavior taking into account environment requirements provided the patient M. firmness before a heavy illness, promoted good adaptation to an environment with confidence in myself, high social adaptability, opportunity successfully to carry out duties, hold the work account (worked 39 years after accident. Comparative assessment of operator ability of the patient M. showed good average time of common and difficult sensorimotor reactions with 2 mistakes, high time of reaction for moving object, however decrease in accuracy of reaction from 10-13% to 2% testifies to manifestation in dynamics of insufficiency of real functional reserves of nervous system. Conclusions. Efficiency of psychophysiological adaptation depends not only on a dose of radiation and weight of the transferred disease, but, mostly, on premorbid properties of the identity of the victim and his social and labor installation.

  13. An encapsulated Yersinia pseudotuberculosis is a highly efficient vaccine against pneumonic plague.

    Science.gov (United States)

    Derbise, Anne; Cerdà Marín, Alba; Ave, Patrick; Blisnick, Thierry; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E

    2012-01-01

    Plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis, the recent ancestor of Yersinia pestis, provided protection against bubonic plague. However, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined. The sequenced Y. pseudotuberculosis IP32953 has been irreversibly attenuated by deletion of genes encoding three essential virulence factors. An encapsulated Y. pseudotuberculosis was generated by cloning the Y. pestis F1-encoding caf operon and expressing it in the attenuated strain. The new V674pF1 strain produced the F1 capsule in vitro and in vivo. Oral inoculation of V674pF1 allowed the colonization of the gut without lesions to Peyer's patches and the spleen. Vaccination induced both humoral and cellular components of immunity, at the systemic (IgG and Th1 cells) and the mucosal levels (IgA and Th17 cells). A single oral dose conferred 100% protection against a lethal pneumonic plague challenge (33×LD(50) of the fully virulent Y. pestis CO92 strain) and 94% against a high challenge dose (3,300×LD(50)). Both F1 and other Yersinia antigens were recognized and V674pF1 efficiently protected against a F1-negative Y. pestis. The encapsulated Y. pseudotuberculosis V674pF1 is an efficient live oral vaccine against pneumonic plague, and could be developed for mass vaccination in tropical endemic areas to control pneumonic plague transmission and mortality.

  14. Experimental model of swine pneumonic pasteurellosis using crude Actinobacillus pleuropneumoniae cytotoxin and Pasteurella multocida given endobronchially.

    OpenAIRE

    Chung, W. B.; Bäckström, L R; Collins, M T

    1994-01-01

    This study was designed to develop and characterize a swine pneumonic pasteurellosis model by concurrent introduction of Pasteurella multocida type A and Actinobacillus pleuropneumoniae crude cytotoxin. After a series of preliminary experiments, a combination of 4 x 10(9) P. multocida and 4,000 toxic units of A. pleuropneumoniae crude cytotoxin was determined to produce optimal results. A total of 48 pigs were divided into four groups of 12 pigs each. The control group received buffered salin...

  15. An Encapsulated Yersinia pseudotuberculosis Is a Highly Efficient Vaccine against Pneumonic Plague

    Science.gov (United States)

    Derbise, Anne; Cerdà Marín, Alba; Ave, Patrick; Blisnick, Thierry; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E.

    2012-01-01

    Background Plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis, the recent ancestor of Yersinia pestis, provided protection against bubonic plague. However, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined. Methodology and Principal Findings The sequenced Y. pseudotuberculosis IP32953 has been irreversibly attenuated by deletion of genes encoding three essential virulence factors. An encapsulated Y. pseudotuberculosis was generated by cloning the Y. pestis F1-encoding caf operon and expressing it in the attenuated strain. The new V674pF1 strain produced the F1 capsule in vitro and in vivo. Oral inoculation of V674pF1 allowed the colonization of the gut without lesions to Peyer's patches and the spleen. Vaccination induced both humoral and cellular components of immunity, at the systemic (IgG and Th1 cells) and the mucosal levels (IgA and Th17 cells). A single oral dose conferred 100% protection against a lethal pneumonic plague challenge (33×LD50 of the fully virulent Y. pestis CO92 strain) and 94% against a high challenge dose (3,300×LD50). Both F1 and other Yersinia antigens were recognized and V674pF1 efficiently protected against a F1-negative Y. pestis. Conclusions and Significance The encapsulated Y. pseudotuberculosis V674pF1 is an efficient live oral vaccine against pneumonic plague, and could be developed for mass vaccination in tropical endemic areas to control pneumonic plague transmission and mortality. PMID:22348169

  16. An encapsulated Yersinia pseudotuberculosis is a highly efficient vaccine against pneumonic plague.

    Directory of Open Access Journals (Sweden)

    Anne Derbise

    Full Text Available BACKGROUND: Plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis, the recent ancestor of Yersinia pestis, provided protection against bubonic plague. However, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined. METHODOLOGY AND PRINCIPAL FINDINGS: The sequenced Y. pseudotuberculosis IP32953 has been irreversibly attenuated by deletion of genes encoding three essential virulence factors. An encapsulated Y. pseudotuberculosis was generated by cloning the Y. pestis F1-encoding caf operon and expressing it in the attenuated strain. The new V674pF1 strain produced the F1 capsule in vitro and in vivo. Oral inoculation of V674pF1 allowed the colonization of the gut without lesions to Peyer's patches and the spleen. Vaccination induced both humoral and cellular components of immunity, at the systemic (IgG and Th1 cells and the mucosal levels (IgA and Th17 cells. A single oral dose conferred 100% protection against a lethal pneumonic plague challenge (33×LD(50 of the fully virulent Y. pestis CO92 strain and 94% against a high challenge dose (3,300×LD(50. Both F1 and other Yersinia antigens were recognized and V674pF1 efficiently protected against a F1-negative Y. pestis. CONCLUSIONS AND SIGNIFICANCE: The encapsulated Y. pseudotuberculosis V674pF1 is an efficient live oral vaccine against pneumonic plague, and could be developed for mass vaccination in tropical endemic areas to control pneumonic plague transmission and mortality.

  17. The yersiniabactin transport system is critical for the pathogenesis of bubonic and pneumonic plague.

    Science.gov (United States)

    Fetherston, Jacqueline D; Kirillina, Olga; Bobrov, Alexander G; Paulley, James T; Perry, Robert D

    2010-05-01

    Iron acquisition from the host is an important step in the pathogenic process. While Yersinia pestis has multiple iron transporters, the yersiniabactin (Ybt) siderophore-dependent system plays a major role in iron acquisition in vitro and in vivo. In this study, we determined that the Ybt system is required for the use of iron bound by transferrin and lactoferrin and examined the importance of the Ybt system for virulence in mouse models of bubonic and pneumonic plague. Y. pestis mutants unable to either transport Ybt or synthesize the siderophore were both essentially avirulent via subcutaneous injection (bubonic plague model). Surprisingly, via intranasal instillation (pneumonic plague model), we saw a difference in the virulence of Ybt biosynthetic and transport mutants. Ybt biosynthetic mutants displayed an approximately 24-fold-higher 50% lethal dose (LD(50)) than transport mutants. In contrast, under iron-restricted conditions in vitro, a Ybt transport mutant had a more severe growth defect than the Ybt biosynthetic mutant. Finally, a Delta pgm mutant had a greater loss of virulence than the Ybt biosynthetic mutant, indicating that the 102-kb pgm locus encodes a virulence factor, in addition to Ybt, that plays a role in the pathogenesis of pneumonic plague.

  18. The Yersiniabactin Transport System Is Critical for the Pathogenesis of Bubonic and Pneumonic Plague▿

    Science.gov (United States)

    Fetherston, Jacqueline D.; Kirillina, Olga; Bobrov, Alexander G.; Paulley, James T.; Perry, Robert D.

    2010-01-01

    Iron acquisition from the host is an important step in the pathogenic process. While Yersinia pestis has multiple iron transporters, the yersiniabactin (Ybt) siderophore-dependent system plays a major role in iron acquisition in vitro and in vivo. In this study, we determined that the Ybt system is required for the use of iron bound by transferrin and lactoferrin and examined the importance of the Ybt system for virulence in mouse models of bubonic and pneumonic plague. Y. pestis mutants unable to either transport Ybt or synthesize the siderophore were both essentially avirulent via subcutaneous injection (bubonic plague model). Surprisingly, via intranasal instillation (pneumonic plague model), we saw a difference in the virulence of Ybt biosynthetic and transport mutants. Ybt biosynthetic mutants displayed an ∼24-fold-higher 50% lethal dose (LD50) than transport mutants. In contrast, under iron-restricted conditions in vitro, a Ybt transport mutant had a more severe growth defect than the Ybt biosynthetic mutant. Finally, a Δpgm mutant had a greater loss of virulence than the Ybt biosynthetic mutant, indicating that the 102-kb pgm locus encodes a virulence factor, in addition to Ybt, that plays a role in the pathogenesis of pneumonic plague. PMID:20160020

  19. Interstitial pneumonitis following total body irradiation for bone marrow transplantation using two different dose rates

    Energy Technology Data Exchange (ETDEWEB)

    Kim, T.H.; Rybka, W.B.; Lehnert, S.; Podgorsak, E.B.; Freeman, C.R.

    1985-07-01

    A total of 22 patients with leukemia have undergone allogeneic bone marrow transplantation (BMT) by the Quebec Co-operative Group for Marrow Transplantation from 1980 to 1982. All patients received 900 cGy total body irradiation (TBI), in a single fraction, on the day preceding BMT. The first 11 patients were treated on a cobalt unit at a constant dose rate of 4.7 to 6.3 cGy/min. Six of these patients developed interstitial pneumonitis (IP). The clinical course of three patients, two with idiopathic and one with drug-induced pneumonitis, was mild and recovery was complete in all. The other three patients developed severe infectious IP and two died. The next 11 patients were treated with a sweeping beam technique on a 4 MV linear accelerator delivering a total tumor dose of 900 cGy at an average dose rate of 6.0 to 6.5 cGy/min but an instantaneous dose rate of 21.0 to 23.5 cGy/min. Eight patients developed severe IP. Five of these were idiopathic and four died. Three were infectious and all died. The fatality of interstitial pneumonitis appeared to be greater in the group treated with the sweeping beam technique.

  20. Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis.

    Science.gov (United States)

    Tan, Susanna K; Burgener, Elizabeth B; Waggoner, Jesse J; Gajurel, Kiran; Gonzalez, Sarah; Chen, Sharon F; Pinsky, Benjamin A

    2016-01-01

    Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results.  Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P ≤ .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions.  Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis.

  1. Gallium-67 scanning in the staging of cryptogenetic fibrosing alveolitis and hypersensitivity pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Vanderstappen, M.; Mornex, J.F.; Lahneche, B.; Chauvot, P.; Bouvier, J.F.; Wiesendanger, T.; Pages, J.; Webert, P.; Cordier, J.F.; Brune, J.

    1988-01-01

    Gallium-67 citrate is known to localize within inflammatory sites. Gallium-67 scanning is used for the evaluation of lung inflammation (i.e. alveolitis) during interstitial lung diseases. We investigated 27 patients with cryptogenetic fibrosing alveolitis (n=17) and hypersensitivity pneumonitis (n=10) using gallium-67 lung scanning and lung function tests (forced vital capacity, diffusing capacity, resting and exercise blood gases). Investigations were performed before and after one year of methylprednisolone treatment. None of eight healthy volunteers had any abnormal gallium-67 uptake. In all patients with cryptogenetic fibrosing alveolitis and initial abnormal gallium-67 uptake was observed (mean fixation index: 163+-18). In addition, analysis of lung function tests a year after initial evaluation showed that unchanged or improving patients presented initially with a lower gallium-67 index than patients with evidence of deterioration (163.9+-23.7 vs 251.0+-23.3.; p<0.01). Similarly, among patients with hypersensitivity pneumonitis the index was lower in unchanged or improving patients than in those with deterioration (74.0+-22 vs 226.7+-4.9; p<0.05). Thus gallium-67 scanning is useful in the management of cryptogenetic fibrosing alveolitis and hypersensitivity pneumonitis.

  2. Radiation-induced stress response in peripheral blood of breast cancer patients differs between patients with severe acute skin reactions and patients with no side effects to radiotherapy.

    Science.gov (United States)

    Skiöld, Sara; Naslund, Ingemar; Brehwens, Karl; Andersson, Arja; Wersall, Peter; Lidbrink, Elisabet; Harms-Ringdahl, Mats; Wojcik, Andrzej; Haghdoost, Siamak

    2013-08-30

    The aim of the study was to compare the radiation-induced oxidative stress response in blood samples from breast cancer patients that developed severe acute skin reactions during the radiotherapy, with the response in blood samples from patients with no side effects. Peripheral blood was collected from 12 breast cancer patients showing no early skin reactions after radiotherapy (RTOG grade 0) and from 14 breast cancer patients who developed acute severe skin reactions (RTOG grade 3-4). Whole blood was irradiated with 0, 5 and 2000mGy γ-radiation and serum was isolated. The biomarker for oxidative stress, 8-oxo-dG, was analyzed in the serum by a modified ELISA. While a significant radiation-induced increase of serum 8-oxo-dG levels was observed in serum of the RTOG 0 patients, no increase was seen in serum of the RTOG 3-4 patients. The radiation induced increase in serum 8-oxo-dG levels after 5mGy did not differ significantly from the increase observed for 2000mGy in the RTOG 3-4 cohort, thus no dose response relation was observed. A receiver operating characteristic (ROC) value of 0.97 was obtained from the radiation-induced increase in 8-oxo-dG indicating that the assay could be used to identify patients with severe acute adverse reactions to radiotherapy. The results show that samples of whole blood from patients, classified as highly radiosensitive (RTOG 3-4) based on their skin reactions to radiotherapy, differ significantly in their oxidative stress response to ionizing radiation compared to samples of whole blood from patients with no skin reactions (RTOG 0). Extracellular 8-oxo-dG is primarily a biomarker of nucleotide damage and the results indicate that the patients with severe acute skin reactions differ in their cellular response to ionizing radiation at the level of induction of oxidative stress or at the level of repair or both. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination.

    Science.gov (United States)

    Derbise, Anne; Hanada, Yuri; Khalifé, Manal; Carniel, Elisabeth; Demeure, Christian E

    2015-01-01

    No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis. VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral

  4. Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination.

    Directory of Open Access Journals (Sweden)

    Anne Derbise

    Full Text Available No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably.The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50 caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50. Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1- Y. pestis.VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single

  5. Clarithromycin-induced acute interstitial nephritis and minimal change disease.

    Science.gov (United States)

    Russell, Wendy; Smith, William

    2009-10-01

    Drug associated acute interstitial nephritis and minimal change disease has been well documented but the simultaneous presentation of both is rare and has not been reported with clarithromycin. We describe a case of simultaneous acute tubulointerstitial nephritis and minimal change disease induced by clarithromycin. The patient had acute kidney injury, nephrotic syndrome, eosinophilic pneumonitis and a maculopapular skin rash. The role of steroid therapy in acute interstitial nephritis is controversial but is accepted as beneficial in minimal change nephrotic syndrome. Steroid therapy in our patient resulted in complete clinical resolution.

  6. Do human lymphocytes exposed to the fallout of the Chernobyl accident exhibit an adaptive response? Part 3. Challenge with bleomycin in lymphocytes from children hit by the initial acute dose of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Tedeschi, Bruna; Caporossi, Daniela; Vernole, Patrizia [Department of Public Health and Cell Biology, University of Rome `Tor Vergata`, Rome (Italy); Padovani, Laura; Mauro, Francesco [Environmental Department, ENEA Casaccia, Rome (Italy)

    1996-07-05

    In the present paper, we report data on the possible adaptive response, induced in vivo by exposure to ionizing radiation to a challenge treatment with the radiomimetic glycopeptide bleomycin (BLM). Lymphocytes from children living in Pripjat at the time of the Chernobyl accident, and thus hit by the initial acute dose of ionizing radiation, were treated for the last 5 h of culture with 0.004 U/ml BLM. Significantly lower chromosome damage was found only in lymphocytes from children who, independently of the initial acute exposure to ionizing radiation, still showed a {sup 137}Cs internal contamination, due to persistent continuous exposure to low doses of radiation. The present results indicate that past exposure to acute high dose of ionizing radiation does not interfere with resistance to BLM which is related to internal contamination.

  7. Reduction of radiation pneumonitis by V20-constraints in breast cancer

    Directory of Open Access Journals (Sweden)

    Svane Gunilla

    2010-10-01

    Full Text Available Abstract Introduction Adjuvant local-regional radiotherapy (LRRT is routinely recommended for breast cancer patients. It is well known being related to pulmonary side-effects. We studied post-RT radiological changes on X-ray and CT, and correlated the findings with Quality of Life (QoL, common dosimetric factors and co-variates. The results were compared with a previously reported cohort of 137 irradiated women. Methods 88 women underwent chest X-ray and CT pre-and 4-5 months after 3-D planned LRRT, minimizing the dose to the ipsilateral lung to V20 13, V20, V30 and mean dose were calculated and QoL was assessed before and 4 months after RT. Results The use of dose-volume constraints significally reduced moderate-severe radiological changes on chest X-ray compared with our earlier study (Chi square trend test: p 13 correlated independently with radiological changes on CT (logistic regression: p = 0.04; ROC area: 0.7. The Co-variates smoking habits, age, chemotherapy, endocrine or trastuzumab therapy did not influence the outcome on multivariate analysis. QoL changes in physical function, i.e. fatigue, dyspnoea were not detected but there was a trend for a worse recovery after chemotherapy in patients with high V13 (Spearman Rank Correlation: p Conclusions The use of dose-volume constraints significantly reduced post-RT radiological changes on chest X-ray in LRRT for BC. The lung changes on CT were also generally limited when we used this strategy and was not always picked up on chest X-ray. Variation in V13 alone was correlated with occurrence of lung changes on CT.

  8. Radiation pneumonitis in non‑small‑cell lung cancer patients treated ...

    African Journals Online (AJOL)

    Conclusions: We found that poor PS and V5–V15 were the risk factors associated with grade ≥3 RP in NSCLC patients treated with HT. Thus, for NSCLC patients treated with HT, the volume of total lung with low-dose ..... Adenocarcinoma.

  9. Toxicity risk of non-target organs at risk receiving low-dose radiation: case report

    Directory of Open Access Journals (Sweden)

    Chen Yu-Jen

    2009-12-01

    Full Text Available Abstract The spine is the most common site for bone metastases. Radiation therapy is a common treatment for palliation of pain and for prevention or treatment of spinal cord compression. Helical tomotherapy (HT, a new image-guided intensity modulated radiotherapy (IMRT, delivers highly conformal dose distributions and provides an impressive ability to spare adjacent organs at risk, thus increasing the local control of spinal column metastases and decreasing the potential risk of critical organs under treatment. However, there are a lot of non-target organs at risk (OARs occupied by low dose with underestimate in this modern rotational IMRT treatment. Herein, we report a case of a pathologic compression fracture of the T9 vertebra in a 55-year-old patient with cholangiocarcinoma. The patient underwent HT at a dose of 30 Gy/10 fractions delivered to T8-T10 for symptom relief. Two weeks after the radiotherapy had been completed, the first course of chemotherapy comprising gemcitabine, fluorouracil, and leucovorin was administered. After two weeks of chemotherapy, however, the patient developed progressive dyspnea. A computed tomography scan of the chest revealed an interstitial pattern with traction bronchiectasis, diffuse ground-glass opacities, and cystic change with fibrosis. Acute radiation pneumonitis was diagnosed. Oncologists should be alert to the potential risk of radiation toxicities caused by low dose off-targets and abscopal effects even with highly conformal radiotherapy.

  10. Comparison of Radiation-Induced Bystander Effect in QU-DB Cells after Acute and Fractionated Irradiation: An In Vitro Study.

    Science.gov (United States)

    Soleymanifard, Shokouhozaman; Bahreyni Toossi, Mohammad Taghi; Kamran Samani, Roghayeh; Mohebbi, Shokoufeh

    2016-01-01

    Radiation effects induced in non-irradiated cells are termed radiation-induced bystander effects (RIBE). The present study intends to examine the RIBE response of QU-DB bystander cells to first, second and third radiation fractions and compare their cumulative outcome with an equal, single acute dose. This experimental study irradiated three groups of target cells for one, two and three times with(60)Co gamma rays. One hour after irradiation, we transferred their culture media to non-irradiated (bystander) cells. We used the cytokinesis block micronucleus assay to evaluate RIBE response in the bystander cells. The numbers of micronuclei generated in bystander cells were determined. RIBE response to single acute doses increased up to 4 Gy, then decreased, and finally at the 8 Gy dose disappeared. The second and third fractions induced RIBE in bystander cells, except when RIBE reached to the maximum level at the first fraction. We split the 4 Gy acute dose into two fractions, which decreased the RIBE response. However, fractionation of 6 Gy (into two fractions of 3 Gy or three fractions of 2 Gy) had no effect on RIBE response. When we split the 8 Gy acute dose into two fractions we observed RIBE, which had disappeared following the single 8 Gy dose. The impact of dose fractionation on RIBE induced in QU-DB cells de- pended on the RIBE dose-response relationship. Where RIBE increased proportion- ally with the dose, fractionation reduced the RIBE response. In contrast, at high dos- es where RIBE decreased proportionally with the dose, fractionation either did not change RIBE (at 6 Gy) or increased it (at 8 Gy).

  11. Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Osti, Mattia Falchetto [Institute of Radiation Oncology, La Sapienza University, Sant' Andrea Hospital, Rome (Italy); Agolli, Linda, E-mail: lindaagolli@yahoo.it [Institute of Radiation Oncology, La Sapienza University, Sant' Andrea Hospital, Rome (Italy); Valeriani, Maurizio; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Enrici, Riccardo Maurizi [Institute of Radiation Oncology, La Sapienza University, Sant' Andrea Hospital, Rome (Italy)

    2013-03-01

    Purpose: Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Methods and Materials: Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. Results: The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Conclusions: Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized

  12. Efficacy of synbiotics to reduce acute radiation proctitis symptoms and improve quality of life: a randomized, double-blind, placebo-controlled pilot trial.

    Science.gov (United States)

    Nascimento, Mariana; Aguilar-Nascimento, José Eduardo; Caporossi, Cervantes; Castro-Barcellos, Heloisa Michelon; Motta, Rodrigo Teixeira

    2014-10-01

    To evaluate whether the daily intake of synbiotics interferes in radiation-induced acute proctitis symptoms and in quality of life in patients with prostate cancer. Twenty patients who underwent 3-dimensional conformal radiation therapy for prostate cancer were randomized to intake either a synbiotic powder containing Lactobacillus reuteri 10(8) colony-forming units and 4.3 g of soluble fiber (Nestlé) or placebo. The questionnaire EORTC QLQ-PRT23 was applied before the beginning of radiation therapy and in every week for the first 4 weeks of treatment. The sum of both the complete (proctitis symptoms plus quality of life) and partial (proctitis symptoms) scores of the EORTC QLQ-PRT23 (European Organization for Research and Treatment of Cancer Quality of Life Module for Proctitis-23 items) questionnaire were the main endpoints. This pilot study showed that the complete questionnaire score (median [range]) was higher in the second (23 [21-30] vs 26.5 [22-34], P<.05) and third (23 [21-32] vs 27.5 [24-33], P<.01) weeks in the placebo group. Proctitis symptoms were highest scored in the placebo group in both the second (19.5 [16-25]) and third (19 [17-24]) weeks than in the synbiotic group (week 2: 16.5 [15-20], P<.05; week 3: 17 [15-23], P<.01). In both scores the placebo group had a significantly higher result (P<.01) than the synbiotic group (repeated-measures analysis of variance). Synbiotics reduce proctitis symptoms and improve quality of life in radiation-induced acute proctitis during radiation therapy for prostate cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Efficacy of Synbiotics to Reduce Acute Radiation Proctitis Symptoms and Improve Quality of Life: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial

    Energy Technology Data Exchange (ETDEWEB)

    Nascimento, Mariana, E-mail: mari1980hemato@yahoo.com.br [Department of Medicine, University Center of Varzea Grande (UNIVAG), Varzea Grande, Mato Grosso (Brazil); Aguilar-Nascimento, José Eduardo [Department of Medicine, University Center of Varzea Grande (UNIVAG), Varzea Grande, Mato Grosso (Brazil); Caporossi, Cervantes; Castro-Barcellos, Heloisa Michelon; Motta, Rodrigo Teixeira [Department of Medicine, Federal University of Mato Grosso (UFMT), Cuiabá, Mato Grosso (Brazil)

    2014-10-01

    Purpose: To evaluate whether the daily intake of synbiotics interferes in radiation-induced acute proctitis symptoms and in quality of life in patients with prostate cancer. Methods and Materials: Twenty patients who underwent 3-dimensional conformal radiation therapy for prostate cancer were randomized to intake either a synbiotic powder containing Lactobacillus reuteri 10{sup 8} colony-forming units and 4.3 g of soluble fiber (Nestlé) or placebo. The questionnaire EORTC QLQ-PRT23 was applied before the beginning of radiation therapy and in every week for the first 4 weeks of treatment. The sum of both the complete (proctitis symptoms plus quality of life) and partial (proctitis symptoms) scores of the EORTC QLQ-PRT23 (European Organization for Research and Treatment of Cancer Quality of Life Module for Proctitis–23 items) questionnaire were the main endpoints. Results: This pilot study showed that the complete questionnaire score (median [range]) was higher in the second (23 [21-30] vs 26.5 [22-34], P<.05) and third (23 [21-32] vs 27.5 [24-33], P<.01) weeks in the placebo group. Proctitis symptoms were highest scored in the placebo group in both the second (19.5 [16-25]) and third (19 [17-24]) weeks than in the synbiotic group (week 2: 16.5 [15-20], P<.05; week 3: 17 [15-23], P<.01). In both scores the placebo group had a significantly higher result (P<.01) than the synbiotic group (repeated-measures analysis of variance). Conclusions: Synbiotics reduce proctitis symptoms and improve quality of life in radiation-induced acute proctitis during radiation therapy for prostate cancer.

  14. Comparison of the protective roles of L-carnitine and amifostine against radiation-induced acute ovarian damage by histopathological and biochemical methods

    Directory of Open Access Journals (Sweden)

    Vuslat Yurut-Caloglu

    2015-01-01

    Full Text Available Purpose: The aim of this study was to compare the radioprotective efficacies of L-carnitine (LC and amifostine against radiation-induced acute ovarian damage. Materials and Methods: Forty-five, 3-month-old Wistar albino rats were randomly assigned to six groups. Control (CONT, n = 7; irradiation alone RT: radiation therapy (RT, n = 8; amifostine plus irradiation (AMI + RT, n = 8; LC plus irradiation (LC + RT, n = 8; LC and sham irradiation (LC, n = 7; and amifostine and sham irradiation (AMI, n = 7. The rats in the AMI + RT, LC + RT and RT groups were irradiated with a single dose of 20 Gy to the whole abdomen. LC (300 mg/kg and amifostine (200 mg/kg was given intraperitoneally 30 min before irradiation. Five days after irradiation, both antral follicles and corpus luteum in the right ovaries were counted, and tissue levels of malondialdehyde (MDA and advanced oxidation protein product (AOPP were measured. Results: Irradiation significantly decreased antral follicles and corpus luteum (P: 0.005 and P 0.05. The level of MDA and AOPP significantly increased after irradiation (P = 0.001 and P 0.005. The levels of both MDA and AOPP were also similar when LC + RT is compared with AMI + RT group (P > 0.005. Conclusions: L-carnitine and amifostine have a noteworthy and similar radioprotective effect against radiation-induced acute ovarian toxicity.

  15. 急性大面积放射线烧伤及其并发症的救治%Treatment of extensive acute radiation burn and its complications

    Institute of Scientific and Technical Information of China (English)

    李叶扬; 汪锦伦; 李罡; 林伟华; 梁岷; 黄峻; 孙敬恩

    2013-01-01

    This article reports the treatment of a patient suffered from acute radiation burn covering 41% TBSA,with deep partial-thickness and full-thickness injury,produced by exposure to a large-scale industrial electron accelerator.An open wound began to appear and enlarged gradually 10 weeks after the exposure.Serious wound infection with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa,pneumonia,respiratory failure,systemic inflammatory response syndrome,nephropathy and hypoproteinemia developed successively since 3 weeks after the wound formation.Skin grafts failed to survive,resulting in enlargement of the wound.After being treated with proper measures,including parenteral nutrition,respiratory support with a ventilator,appropriate antibiotics,steroid administration for nephropathy,deep debridement for wounds followed by skin grafting,the patient was cured and discharged after undergoing 15 operations in 500 days.The clinical condition of an extensive acute radiation burn is complicated.We should pay close attention to the changes in functions of organs,and strengthen the therapeutic strategies to support the function of organs to reduce the incidence of systemic complications.The control of the infection and the timely and effective repair of the wound are stiil the key points of the treatment of an extensive local radiation injury.

  16. An experimental study on acute brain radiation injury: Dynamic changes in proton magnetic resonance spectroscopy and the correlation with histopathology

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hui, E-mail: lihui@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou (China); Li, Jian-peng, E-mail: lijp@sysucc.org.cn [Department of Radiology, Dongguan People' s Hospital, Dongguan City (China); Lin, Cheng-guang, E-mail: linchg@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou (China); Liu, Xue-wen, E-mail: liuxw@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou (China); Geng, Zhi-jun, E-mail: gengzhj@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou (China); Mo, Yun-xian, E-mail: moyx@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou (China); Zhang, Rong, E-mail: zhangr@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou (China); Xie, Chuan-miao, E-mail: xchuanm@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou (China)

    2012-11-15

    Purpose: To investigate the correlation between the alterations of single-voxel {sup 1}H MRS and the histopathological characteristics of radiation brain injury following radiation. Materials and methods: Twenty-seven rabbits were randomized into nine groups to receive radiation with a single dose of 25 Gy. The observation time points included a pre-radiation and 1, 2, 3, 4, 5, 6, 7, and 8 wk following radiation. Each treatment group underwent conventional MRI and single-voxel {sup 1}H MRS, N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) were observed over the region of interest, and the presence or absence of lactate (Lac) and lipid (Lip) was detected. Histological specimens of each group were obtained after image acquisition. Results: The values of Cho were significantly increased in the first 3 wk, and decreased over the following 5 wk after radiation. Levels of NAA showed a trend toward a decrease 5 wk after radiation. The levels of Cr were not changed between before and after radiation. The Cho/NAA metabolic ratio was significantly increased in weeks 6, 7, and 8 following irradiation, compared to pre-radiation values. Vascular and glial injury appeared on 2 wk after RT in the histology samples, until 4 wk after RT, necrosis of the oligodendrocytes, neuronal degeneration and demyelination could be observed. Conclusions: MRS is sensitive to detect metabolic changes following radiation, and can be used in the early diagnosis of radiation brain injury.

  17. TU-G-BRA-08: BEST IN PHYSICS (JOINT IMAGING-THERAPY): Hybrid PET-MRI Imaging of Acute Radiation Induced Cardiac Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    El-Sherif, O; Xhaferllari, I; Gaede, S [Western Univeristy, London, ON (United Kingdom); London Regional Cancer Program, London, ON (United Kingdom); Sykes, J; Butler, J [Lawson Health Research Institute, London, ON (United Kingdom); Wisenberg, G; Prato, F [Western Univeristy, London, ON (United Kingdom); Lawson Health Research Institute, London, ON (United Kingdom)

    2015-06-15

    Purpose: To identify the presence of low-dose radiation induced cardiac toxicity in a canine model using hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: Research ethics board approval was obtained for a longitudinal imaging study of 5 canines after cardiac irradiation. Animals were imaged at baseline, 1 week post cardiac irradiation, and 1 month post cardiac irradiation using a hybrid PET- MRI system (Biograph mMR, Siemens Healthcare). The imaging protocol was designed to assess acute changes in myocardial perfusion and inflammation. Myocardial perfusion imaging was performed using N13-ammonia tracer followed by a dynamic PET acquisition scan. A compartmental tracer kinetic model was used for absolute perfusion quantification. Myocardial inflammation imaging was performed using F18-fluorodeoxyglucose (FDG) tracer. The standard uptake value (SUV) over a region encompassing the whole heart was used to compare FDG scans. All animals received a simulation CT scan (GE Medical Systems) for radiation treatment planning. Radiation treatment plans were created using the Pinncale3 treatment planning system (Philips Radiation Oncology Systems) and designed to resemble the typical cardiac exposure during left-sided breast cancer radiotherapy. Cardiac irradiations were performed in a single fraction using a TrueBeam linear accelerator (Varian Medical Systems). Results: The delivered dose (mean ± standard deviation) to heart was 1.8±0.2 Gy. Reductions in myocardial stress perfusion relative to baseline were observed in 2 of the 5 animals 1 month post radiation. A global inflammatory response 1 month post radiation was observed in 4 of the 5 animals. The calculated SUV at 1 month post radiation was significantly higher (p=0.05) than the baseline SUV. Conclusion: Low doses of cardiac irradiation (< 2 Gy) may lead to myocardial perfusion defects and a global inflammatory response that can be detectable as early as 1 month post irradiation

  18. Thin-Section CT Characteristics and Longitudinal CT Follow-up of Chemotherapy Induced Interstitial Pneumonitis

    Science.gov (United States)

    Lee, Han Na; Kim, Mi Young; Koo, Hyun Jung; Kim, Sung-Soo; Yoon, Dok Hyun; Lee, Jae Cheol; Song, Jin Woo

    2016-01-01

    Abstract To describe the computed tomography (CT) features of chemotherapy-induced interstitial pneumonitis (CIIP) with longitudinal follow-up. The study was approved by the local ethics committee. One hundred consecutive patients with CIIP between May 2005 and March 2015 were retrospectively enrolled. The initial CT was reviewed by 2 independent chest radiologists and categorized into 1 of 4 CT patterns in accordance with the 2013 guidelines for idiopathic interstitial pneumonia: nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), hypersensitivity pneumonitis (HP) mimicking desquamative interstitial pneumonitis, and diffuse alveolar damage (DAD). We assessed semiquantitative analysis on a 5% scale to assess the extent of parenchymal abnormalities (emphysema, reticulation, ground-glass opacity, consolidation, honeycombing cyst) and their distribution on initial (n = 100), subsequent (n = 87), and second follow-up CT (n = 48). Interval changes in extent on follow-up CT were compared using paired t test. The clinic-radiologic factors were compared between Group 1 (NSIP and OP patterns) and Group 2 (HP and DAD patterns) using χ2 and independent t tests. The most common pattern of CIIP on the initial CT was HP (51%), followed by NSIP (23%), OP (20%), and DAD (6%). Diffuse ground-glass opacity was the most common pulmonary abnormality. The predominant distribution was bilateral (99%) and symmetric (82%), with no craniocaudal (60%) or axial (79%) dominance. Subsequent and second follow-up CTs showed decreased extent of total pulmonary abnormalities (P CIIP, Group 2 CIIP was more likely to be caused by molecularly targeted drugs (P = 0.030), appeared earlier (P = 0.034), and underwent more complete resolution (P CIIP is appropriate and practical in interpreting radiological findings. PMID:26765442

  19. Relative biological effectiveness of simulated solar particle event proton radiation to induce acute hematological change in the porcine model

    Science.gov (United States)

    Sanzari, Jenine K.; Wan, Steven X.; Diffenderfer, Eric S.; Cengel, Keith A.; Kennedy, Ann R.

    2014-01-01

    The present study was undertaken to determine relative biological effectiveness (RBE) values for simulated solar particle event (SPE) radiation on peripheral blood cells using Yucatan minipigs and electron-simulated SPE as the reference radiation. The results demonstrated a generally downward trend in the RBE values with increasing doses of simulated SPE radiation for leukocytes in the irradiated animals. The fitted RBE values for white blood cells (WBCs), lymphocytes, neutrophils, monocytes and eosinophils were above 1.0 in all three radiation dose groups at all time-points evaluated, and the lower limits of the 95% confidence intervals were > 1.0 in the majority of the dose groups at different time-points, which together suggest that proton-simulated SPE radiation is more effective than electron-simulated SPE radiation in reducing the number of peripheral WBCs, lymphocytes, neutrophils, monocytes and eosinophils, especially at the low end of the 5–10 Gy dose range evaluated. Other than the RBE values, the responses of leukocytes to electron-simulated SPE radiation and proton-simulated SPE radiation exposure are highly similar with respect to the time-course, the most radiosensitive cell type (the lymphocytes), and the shape of the dose–response curves, which is generally log-linear. These findings provide additional evidence that electron-simulated SPE radiation is an appropriate reference radiation for determination of RBE values for the simulated SPE radiations, and the RBE estimations using electron-simulated SPE radiation as the reference radiation are not complicated by other characteristics of the leukocyte response to radiation exposure. PMID:24027300

  20. Relative biological effectiveness of simulated solar particle event proton radiation to induce acute hematological change in the porcine model.

    Science.gov (United States)

    Sanzari, Jenine K; Wan, Steven X; Diffenderfer, Eric S; Cengel, Keith A; Kennedy, Ann R

    2014-03-01

    The present study was undertaken to determine relative biological effectiveness (RBE) values for simulated solar particle event (SPE) radiation on peripheral blood cells using Yucatan minipigs and electron-simulated SPE as the reference radiation. The results demonstrated a generally downward trend in the RBE values with increasing doses of simulated SPE radiation for leukocytes in the irradiated animals. The fitted RBE values for white blood cells (WBCs), lymphocytes, neutrophils, monocytes and eosinophils were above 1.0 in all three radiation dose groups at all time-points evaluated, and the lower limits of the 95% confidence intervals were > 1.0 in the majority of the dose groups at different time-points, which together suggest that proton-simulated SPE radiation is more effective than electron-simulated SPE radiation in reducing the number of peripheral WBCs, lymphocytes, neutrophils, monocytes and eosinophils, especially at the low end of the 5-10 Gy dose range evaluated. Other than the RBE values, the responses of leukocytes to electron-simulated SPE radiation and proton-simulated SPE radiation exposure are highly similar with respect to the time-course, the most radiosensitive cell type (the lymphocytes), and the shape of the dose-response curves, which is generally log-linear. These findings provide additional evidence that electron-simulated SPE radiation is an appropriate reference radiation for determination of RBE values for the simulated SPE radiations, and the RBE estimations using electron-simulated SPE radiation as the reference radiation are not complicated by other characteristics of the leukocyte response to radiation exposure.

  1. No effect of pirfenidone treatment in fulminant bleomycin-induced pneumonitis

    Directory of Open Access Journals (Sweden)

    Elisabeth Bendstrup

    2014-01-01

    Full Text Available Bleomycin-induced pneumonitis (BIP is a serious and potentially fatal adverse effect of bleomycin. Currently, BIP is treated on an empirical basis with high dose steroid. Pirfenidone is a new antifibrotic drug, which has been proven beneficial in idiopathic pulmonary fibrosis and is able to inhibit or reverse BIP in animal models. Here, the first two cases of human BIP treated with pirfenidone in addition to steroid therapy are presented. Unfortunately, both patients died, which may be explained by the initiation of therapy at a late stage. Therefore, studies of early or prophylactic treatment with pirfenidone in relation to bleomycin-containing chemotherapy regimens are needed.

  2. Detection of Mycoplasma ovipneumoniae and Pasteurella haemolytica antigens by an immunoperoxidase technique in pneumonic ovine lungs.

    Science.gov (United States)

    Haziroglu, R; Diker, K S; Turkarslan, J; Gulbahar, M Y

    1996-01-01

    Four hundred twenty pneumonic lungs from lambs were examined for Mycoplasma ovipneumoniae and Pasteurella haemolytica by an immunoperoxidase technique using an extravidin-biotin-peroxidase complex method in formalin-fixed, paraffin-embedded sections. Histologic examination of tissue sections revealed strong positive reactions in 60.9% and 68.3% of the lungs against M. ovipneumoniae and P. haemolytica, respectively. M. ovipneumoniae and P. haemolytica antigens were observed at the surface and/or within the epithelial cells, macrophages, leucocytes, and bronchiolar exudate. The location of M. ovipneumoniae in the cytoplasm of the epithelial cells and P. haemolytica in the neutrophils was detected immunohistochemically.

  3. Delayed onset, protracted delirium and aspiration pneumonitis associated with a combination of clozapine and electroconvulsive therapy

    Directory of Open Access Journals (Sweden)

    N Manjunatha

    2011-01-01

    Full Text Available Few studies reported the efficacy and safety in combination of clozapine and electroconvulsive therapy (ECT in schizophrenia; systematic studies are lacking. Side effects like seizure, and confusional state are reported. Authors report two cases of delayed onset/protracted delirium with ECT and clozapine in schizophrenia, one of whom developed aspiration pneumonitis possibly due to clozapine hyper-salivation. Delirium improved with stopping of ECT and clozapine. Clozapine monotherapy restarted to previous dosages in both cases without recurrence of delirium. Authors recommend for careful monitoring for delirium in ECT augmentation on high dose clozapine. Unilateral ECT may be preferred for augmenting clozapine.

  4. sup 133 Xe ventilation study in pulmonary infiltration with eosinophilia and hypersensitivity pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Akaki, Shiro; Kohno, Yoshihiro; Yasui, Kotaro (Okayama Univ. (Japan). School of Medicine) (and others)

    1990-09-01

    Ventilation study using {sup 133}Xe were performed to measure regional ventilation in four normal volunteers, four patients with pulmonary infiltration with eosinophilia (PIE) and five patients with hypersensitivity pneumonitis (HP). In both PIE and HP, regional abnormality of ventilation was seen and two indexes of ventilation T{sub 1/2}, T{sub A/H} were in a tendency to be longer in PIE and HP than in normal volunteers. It was suggested that {sup 133}Xe ventilation study might be useful for PIE and HP. (author).

  5. BCG pneumonitis with a miliary radiological pattern complicating intravesical BCG immunotherapy

    Directory of Open Access Journals (Sweden)

    Evangelia Fouka

    2010-01-01

    Full Text Available SUMMARY. The case is described of a 42 year-old male who presented with fever, haematuria, hypoxaemia, impaired liver function and a miliary pattern on chest X-ray while receiving intravesical BCG treatment for superficial bladder cancer. Initiation of antituberculous therapy resulted in rapid amelioration of the symptoms and the X-ray findings, and the patient left hospital in a good general state of health. Although M. bovis was not isolated from samples of sputum, bronchioalveolar lavage fluid (BALF or bronchial biopsy tissue, the prompt response to antituberculous therapy suggests an infectious aetiology due to microbial dissemination. Pneumon 2010, 23(4:388-391.

  6. Drug Induced Pneumonitis Secondary to Treatment with Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir (VIEKIRA PAK®) for Chronic Hepatitis C: Case Report of an Unexpected Life-Threatening Adverse Reaction

    Science.gov (United States)

    Faire, Bridget; Gane, Edward

    2017-01-01

    VIEKIRA PAK (ritonavir-boosted paritaprevir/ombitasvir and dasabuvir) is an approved treatment for compensated patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection. This oral regimen has minimal adverse effects and is well tolerated. Cure rates are 97% in patients infected with HCV GT 1a and 99% in those with HCV GT 1b. We report the first case of life-threatening allergic pneumonitis associated with VIEKIRA PAK. This unexpected serious adverse event occurred in a 68-year-old Chinese female with genotype 1b chronic hepatitis C and Child-Pugh A cirrhosis. One week into treatment with VIEKIRA PAK without ribavirin, she was admitted to hospital with respiratory distress and acute kidney injury requiring intensive care input. She was initially diagnosed with community acquired pneumonia and improved promptly with intravenous antibiotics and supported care. No bacterial or viral pathogens were cultured. Following complete recovery, she recommenced VIEKIRA PAK but represented 5 days later with more rapidly progressive respiratory failure, requiring intubation and ventilation, inotropic support, and haemodialysis. The final diagnosis was drug induced pneumonitis.

  7. Reconstruction of the Radiation Emergency Medical System From the Acute to the Sub-acute Phases After the Fukushima Nuclear Power Plant Crisis.

    Science.gov (United States)

    Ojino, Mayo; Ishii, Masami

    2014-02-01

    The radiation emergency medical system in Japan ceased to function as a result of the accident at the Fukushima Daiichi Nuclear Power Plant, which has commonly become known as the "Fukushima Accident." In this paper, we review the reconstruction processes of the radiation emergency medical system in order of events and examine the ongoing challenges to overcoming deficiencies and reinforcing the system by reviewing relevant literature, including the official documents of the investigation committees of the National Diet of Japan, the Japanese government, and the Tokyo Electric Power Company, as well as technical papers written by the doctors involved in radiation emergency medical activities in Fukushima. Our review has revealed that the reconstruction was achieved in 6 stages from March 11 to July 1, 2011: (1) Re-establishment of an off-site center (March 13), (2) Re-establishment of a secondary radiation emergency hospital (March 14), (3) Reconstruction of the initial response system for radiation emergency care (April 2), (4) Reinforcement of the off-site center and stationing of disaster medical advisors at the off-site center (April 4), (5) Reinforcement of the medical care system and an increase in the number of hospitals for non-contaminated patients (From April 2 to June 23), and (6) Enhancement of the medical care system in the Fukushima Nuclear Power Plant and the construction of a new medical care system, involving both industrial medicine and emergency medicine (July 1). Medical resources such as voluntary efforts, academic societies, a local community medical system and university hospitals involved in medical care activities on 6 stages originally had not planned. In the future, radiation emergency medical systems should be evaluated with these 6 stages as a basis, in order to reinforce and enrich both the existing and backup systems so that minimal harm will come to nuclear power plant workers or evacuees and that they will receive proper care. This

  8. Severe acute respiratory syndrome (SARS) in Hong Kong.

    Science.gov (United States)

    Tsang, Kenneth W; Mok, Thomas Y; Wong, Poon C; Ooi, Gaik C

    2003-09-01

    Severe acute respiratory syndrome (SARS) is a recently recognized and highly contagious pneumonic illness, caused by a novel coronavirus. While developments in diagnostic, clinical and other aspects of SARS research are well underway, there is still great difficulty for frontline clinicians as validated rapid diagnostic tests or effective treatment regimens are lacking. This article attempts to summarize some of the recent developments in this newly recognized condition from the Asia Pacific perspective.

  9. Scenario of a dirty bomb in an urban environment and acute management of radiation poisoning and injuries

    National Research Council Canada - National Science Library

    Chin, F K C

    2007-01-01

    .... This article examines two scenarios of radiation contamination and injury, one accidental in nature leading to environmental contamination, and another of deliberate intent resulting in injury and death...

  10. Inhaled Liposomal Ciprofloxacin Protects against a Lethal Infection in a Murine Model of Pneumonic Plague

    Science.gov (United States)

    Hamblin, Karleigh A.; Armstrong, Stuart J.; Barnes, Kay B.; Davies, Carwyn; Laws, Thomas; Blanchard, James D.; Harding, Sarah V.; Atkins, Helen S.

    2017-01-01

    Inhalation of Yersinia pestis can lead to pneumonic plague, which without treatment is inevitably fatal. Two novel formulations of liposome-encapsulated ciprofloxacin, ‘ciprofloxacin for inhalation’ (CFI, Lipoquin®) and ‘dual release ciprofloxacin for inhalation’ (DRCFI, Pulmaquin®) containing CFI and ciprofloxacin solution, are in development. These were evaluated as potential therapies for infection with Y. pestis. In a murine model of pneumonic plague, human-like doses of aerosolized CFI, aerosolized DRCFI or intraperitoneal (i.p.) ciprofloxacin were administered at 24 h (representing prophylaxis) or 42 h (representing treatment) post-challenge. All three therapies provided a high level of protection when administered 24 h post-challenge. A single dose of CFI, but not DRCFI, significantly improved survival compared to a single dose of ciprofloxacin. Furthermore, single doses of CFI and DRCFI reduced bacterial burden in lungs and spleens to below the detectable limit at 60 h post-challenge. When therapy was delayed until 42 h post-challenge, a single dose of CFI or DRCFI offered minimal protection. However, single doses of CFI or DRCFI were able to significantly reduce the bacterial burden in the spleen compared to empty liposomes. A three-day treatment regimen of ciprofloxacin, CFI, or DRCFI resulted in high levels of protection (90–100% survival). This study suggests that CFI and DRCFI may be useful therapies for Y. pestis infection, both as prophylaxis and for the treatment of plague. PMID:28220110

  11. Chronic hypersensitivity pneumonitis: high resolution computed tomography patterns and pulmonary function indices as prognostic determinants

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, Simon L.F.; Devaraj, Anand; Hansell, David M. [Royal Brompton Hospital, Department of Radiology, London (United Kingdom); Sverzellati, Nicola [University of Parma, Department of Clinical Sciences, Section of Radiology, Parma (Italy); Wells, Athol U. [Royal Brompton Hospital, Interstitial Lung Diseases Unit, London (United Kingdom)

    2012-08-15

    To investigate high resolution computed tomography (HRCT) and pulmonary function indices (PFTs) for determining prognosis in patients with chronic fibrotic hypersensitivity pneumonitis (CHP). Case records, PFTs (FEV{sub 1}, FVC and DLco) and HRCTs of ninety-two patients with chronic hypersensitivity pneumonitis were evaluated. HRCT studies were scored by two observers for total disease extent, ground-glass opacification, fine and coarse reticulation, microcystic and macrocystic honeycombing, centrilobular emphysema and consolidation. Traction bronchiectasis within each pattern was graded. Using Cox proportional hazards regression models the prognostic strength of individual HRCT patterns and pulmonary function test variables were determined. There were forty two deaths during the study period. Increasing severity of traction bronchiectasis was the strongest predictor of mortality (HR 1.10, P < 0.001, 95%CI 1.04-1.16). Increasing global interstitial disease extent (HR 1.02, P = 0.02, 95%CI 1.00-1.03), microcystic honeycombing (HR 1.09, P = 0.019, 95%CI 1.01-1.17) and macrocystic honeycombing (HR 1.06, P < 0.01, 95%CI 1.01-1.10) were also independent predictors of mortality. In contrast, no individual PFT variable was predictive of mortality once HRCT patterns were accounted for. HRCT patterns, in particular, severity of traction bronchiectasis and extent of honeycombing are superior to pulmonary function tests for predicting mortality in patients with CHP. (orig.)

  12. Feed exposure to FB1 can aggravate pneumonic damages in pigs provoked by P. multocida.

    Science.gov (United States)

    Kovács, Melinda; Pósa, Roland; Tuboly, Tamás; Donkó, Tamás; Repa, Imre; Tossenberger, János; Szabó-Fodor, Judit; Stoev, Stoycho; Magyar, Tibor

    2016-10-01

    The possible interaction between Pasteurella multocida and the mycotoxin fumonisin B1 (FB1), recognised as one of the most often food/feed contaminant, was studied with the aim to evaluate whether and how FB1 can influence and/or complicate the development and severity of various pathological damages provoked by Pasteurella multocida in some internal organs of pigs. Heavier lung pathology was seen in pigs experimentally infected with Pasteurella multocida, when the same were exposed to 20ppm dietary levels of fumonisin B1 (FB1) as was assessed by gross pathology, pathomorphological examinations, clinical biochemistry and some immunological investigations. The most typical damages in FB1 treated pigs were the strong oedema in the lung and the slight oedema in the other internal organs and mild degenerative changes in the kidneys, whereas the typical pathomorphological findings in pigs infected with Pasteurella multocida was broncho-interstitial pneumonia. FB1 was found to aggravate pneumonic changes provoked by P. multocida in the cranial lobes of the lung and to complicate pneumonic damages with interstitial oedema in the lung. No macroscopic damages were observed in the pigs infected only with Pasteurella multocida. It can be concluded that the feed intake of FB1 in pigs may complicate or exacerbate the course of P. multocida serotype A infection.

  13. Impact of the Pla protease substrate α2-antiplasmin on the progression of primary pneumonic plague.

    Science.gov (United States)

    Eddy, Justin L; Schroeder, Jay A; Zimbler, Daniel L; Bellows, Lauren E; Lathem, Wyndham W

    2015-12-01

    Many pathogens usurp the host hemostatic system during infection to promote pathogenesis. Yersinia pestis, the causative agent of plague, expresses the plasminogen activator protease Pla, which has been shown in vitro to target and cleave multiple proteins within the fibrinolytic pathway, including the plasmin inhibitor α2-antiplasmin (A2AP). It is not known, however, if Pla inactivates A2AP in vivo; the role of A2AP during respiratory Y. pestis infection is not known either. Here, we show that Y. pestis does not appreciably cleave A2AP in a Pla-dependent manner in the lungs during experimental pneumonic plague. Furthermore, following intranasal infection with Y. pestis, A2AP-deficient mice exhibit no difference in survival time, bacterial burden in the lungs, or dissemination from wild-type mice. Instead, we found that in the absence of Pla, A2AP contributes to the control of the pulmonary inflammatory response during infection by reducing neutrophil recruitment and cytokine production, resulting in altered immunopathology of the lungs compared to A2AP-deficient mice. Thus, our data demonstrate that A2AP is not significantly affected by the Pla protease during pneumonic plague, and although A2AP participates in immune modulation in the lungs, it has limited impact on the course or ultimate outcome of the infection.

  14. [Human plague and pneumonic plague : pathogenicity, epidemiology, clinical presentations and therapy].

    Science.gov (United States)

    Riehm, Julia M; Löscher, Thomas

    2015-07-01

    Yersinia pestis is a highly pathogenic gram-negative bacterium and the causative agent of human plague. In the last 1500 years and during three dreaded pandemics, millions of people became victims of Justinian's plague, the Black Death, or modern plague. Today, Y. pestis is endemic in natural foci of Asian, African and American countries. Due to its broad dissemination in mammal species and fleas, eradication of the pathogen will not be possible in the near future. In fact, plague is currently classified as a "re-emerging disease". Infection may occur after the bite of an infected flea, but also after oral ingestion or inhalation of the pathogen. The clinical presentations comprise the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Most human cases can successfully be treated with antibiotics. However, the high transmission rate and lethality of pneumonic plague require international and mandatory case notification and quarantine of patients. Rapid diagnosis, therapy and barrier nursing are not only crucial for the individual patient but also for the prevention of further spread of the pathogen or of epidemics. Therefore, WHO emergency schedules demand the isolation of cases, identification and surveillance of contacts as well as control of zoonotic reservoir animals and vectors. These sanctions and effective antibiotic treatment usually allow a rapid containment of outbreaks. However, multiple antibiotic resistant strains of Y. pestis have been isolated from patients in the past. So far, no outbreaks with such strains have been reported.

  15. Controlling Ebola: what we can learn from China's 1911 battle against the pneumonic plague in Manchuria.

    Science.gov (United States)

    Liu, He; Jiao, Mingli; Zhao, Siqi; Xing, Kai; Li, Ye; Ning, Ning; Liang, Libo; Wu, Qunhong; Hao, Yanhua

    2015-04-01

    The pneumonic plague, which spread across Northeast China during the winter of 1910 and spring of 1911, caused numerous deaths and brought about severe social turmoil. After compulsory quarantine and other epidemic prevention measures were enforced by Dr Wu Lien-teh, the epidemic was brought to an end within 4 months. This article reviews the ways in which the plague was dealt with from a historical perspective, based on factors such as clinical manifestations, duration of illness, case fatality rate, degree of transmissibility, poverty, inadequate healthcare infrastructure, and the region's recent strife-filled history. Similarities were sought between the pneumonic plague in Northeast China in the twentieth century and the Ebola virus outbreak that is currently ravaging Africa, and an effort made to summarize the ways in which specific measures were applied successfully to fight the earlier epidemic. Our efforts highlight valuable experiences that are of potential benefit in helping to fight the current rampant Ebola epidemic in West Africa. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Controlling Ebola: what we can learn from China's 1911 battle against the pneumonic plague in Manchuria

    Directory of Open Access Journals (Sweden)

    He Liu

    2015-04-01

    Full Text Available The pneumonic plague, which spread across Northeast China during the winter of 1910 and spring of 1911, caused numerous deaths and brought about severe social turmoil. After compulsory quarantine and other epidemic prevention measures were enforced by Dr Wu Lien-teh, the epidemic was brought to an end within 4 months. This article reviews the ways in which the plague was dealt with from a historical perspective, based on factors such as clinical manifestations, duration of illness, case fatality rate, degree of transmissibility, poverty, inadequate healthcare infrastructure, and the region's recent strife-filled history. Similarities were sought between the pneumonic plague in Northeast China in the twentieth century and the Ebola virus outbreak that is currently ravaging Africa, and an effort made to summarize the ways in which specific measures were applied successfully to fight the earlier epidemic. Our efforts highlight valuable experiences that are of potential benefit in helping to fight the current rampant Ebola epidemic in West Africa.

  17. Evaluation of genotoxicity of the acute gamma radiation on earthworm Eisenia fetida using single cell gel electrophoresis technique (Comet assay).

    Science.gov (United States)

    Sowmithra, K; Shetty, N J; Jha, S K; Chaubey, R C

    2015-12-01

    Earthworms (Eisenia fetida) most suitable biological indicators of radioactive pollution. Radiation-induced lesions in DNA can be considered to be molecular markers for early effects of ionizing radiation. Gamma radiation produces a wide spectrum of DNA. Some of these lesions, i.e., DNA strand breaks and alkali labile sites can be detected by the single-cell gel electrophoresis (SCGE) or comet assay by measuring the migration of DNA from immobilized nuclear DNA. E. fetida were exposed to different doses of gamma radiation, i.e., 1, 5, 10, 20, 30, 40 and 50Gy, and comet assay was performed for all the doses along with control at 1, 3 and 5h post irradiation to evaluate the genotoxicity of gamma radiation in this organism. The DNA damage was measured as percentage of comet tail DNA. A significant increase in DNA damage was observed in samples exposed to 5Gy and above, and the increase in DNA damage was dose dependent i.e., DNA damage was increased with increased doses of radiation. The highest DNA damage was noticed at 1h post irradiation and gradually decreased with time, i.e., at 3 and 5h post irradiation. The present study reveals that gamma radiation induces DNA damage in E. fetida and the comet assay is a sensitive and rapid method for its detection to detect genotoxicity of gamma radiation.

  18. Acute Urinary Morbidity Following Stereotactic Body Radiation Therapy for Prostate Cancer with Prophylactic Alpha-Adrenergic Antagonist and Urethral Dose Reduction

    Directory of Open Access Journals (Sweden)

    Michael Charles Repka

    2016-05-01

    Full Text Available Background: Stereotactic body radiation therapy (SBRT delivers high doses of radiation to the prostate while minimizing radiation to adjacent critical organs. Large fraction sizes may increase urinary morbidity due to unavoidable treatment of the prostatic urethra. This study reports rates of acute urinary morbidity following SBRT for localized prostate cancer with prophylactic alpha-adrenergic antagonist utilization and urethral dose reduction (UDR.Methods: From April 2013 to September 2014, 102 patients with clinically localized prostate cancer were treated with robotic SBRT to a total dose of 35-36.25 Gy in 5 fractions. UDR was employed to limit the maximum point dose of the prostatic urethra to 40 Gy. Prophylactic alpha-adrenergic antagonists were initiated five days prior to SBRT and continued until resolution of urinary symptoms. Quality of life (QoL was assessed before and after treatment using the American Urological Association Symptom Score (AUA and the Expanded Prostate Cancer Index Composite-26 (EPIC-26. Clinical significance was assessed using a minimally important difference (MID of one half standard deviation change from baseline.Results: 102 patients underwent definitive prostate SBRT with UDR and were followed for 3 months. No patient experienced acute urinary retention requiring catheterization. A mean baseline AUA symptom score of 9.06 significantly increased to 11.83 one-week post-SBRT (p = 0.0024 and 11.84 one-month post-SBRT (p = 0.0023 but returned to baseline by 3 months. A mean baseline EPIC-26 irritative/obstructive score of 87.7 decreased to 74.1 one-week post-SBRT (p < 0.0001 and 77.8 one-month post-SBRT (p < 0.0001 but returned to baseline at 3 months. EPIC-26 irritative/obstructive score changes were clinically significant, exceeding the MID of 6.0. At baseline, 8.9% of men described their urinary function as a moderate to big problem, and that proportion increased to 37.6% one week following completion of SBRT

  19. Sirolimus-induced pneumonitis complicated by pentamidine-induced phospholipidosis in a renal transplant recipient: a case report.

    Science.gov (United States)

    Filippone, E J; Carson, J M; Beckford, R A; Jaffe, B C; Newman, E; Awsare, B K; Doria, C; Farber, J L

    2011-09-01

    The proliferation signal inhibitors (PSIs)-sirolimus, everolimus, and temsirolimus-have been associated with a noninfectious pneumonitis characterized by lymphocytic alveolitis and bronciolitis obliterans with organizing pneumonia (BOOP). This condition usually occurs within the first year. Herein we presented a case of a deceased donor renal transplant with interstitial pneumonitis developing 6 years after a switch from tacrolimus to sirolimus due to chronic graft dysfunction. After the addition of intravenous pentamidine due to the suspicion of Pneumocystis pneumonia, there was marked clinical deterioration requiring intubation. Open lung biopsy revealed sirolimus-induced pulmonary toxicity (BOOP) with the additional finding of a drug-induced phospholipidosis (DIPL) that we ascribe to pentamidine treatment. After cessation of both drugs and application of corticosteroid therapy, there was only partial improvement. Eight months later the residual interstitial fibrosis demands supplemental home oxygen. We review the literature on PSI-induced pneumonitis and discuss the pathophysiology of a potential interaction with pentamidine. We caution against its use in the setting of PSI-induced pneumonitis. It is currently unknown whether these concerns also apply to prescription of other more commonly used medications associated with DIPL, eg, amiodarone and aminoglycosides.

  20. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    W.E. Kaman (Wendy); S. Hawkey; D. van der Kleij (Desiree); M.P. Broekhuijsen; N.J. Silman; F.J. Bikker (Floris)

    2011-01-01

    textabstractWe determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The

  1. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    Kaman, W.E.; Hawkey, S.; Kleij, D. van der; Broekhuijsen, M.P.; Silman, N.J.; Bikker, F.J.

    2011-01-01

    We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all

  2. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    W.E. Kaman (Wendy); S. Hawkey; D. van der Kleij (Desiree); M.P. Broekhuijsen; N.J. Silman; F.J. Bikker (Floris)

    2011-01-01

    textabstractWe determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virul

  3. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    Kaman, W.E.; Hawkey, S.; Kleij, D. van der; Broekhuijsen, M.P.; Silman, N.J.; Bikker, F.J.

    2011-01-01

    We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all

  4. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    W.E. Kaman (Wendy); S. Hawkey; D. van der Kleij (Desiree); M.P. Broekhuijsen; N.J. Silman; F.J. Bikker (Floris)

    2011-01-01

    textabstractWe determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virul

  5. Timed Get Up and Go Test and Geriatric 8 Scores and the Association With (Chemo-)Radiation Therapy Noncompliance and Acute Toxicity in Elderly Cancer Patients.

    Science.gov (United States)

    Middelburg, Judith G; Mast, Mirjam E; de Kroon, Maaike; Jobsen, Jan J; Rozema, Tom; Maas, Huub; Baartman, Elizabet A; Geijsen, Debby; van der Leest, Annija H; van den Bongard, Desirée J; van Loon, Judith; Budiharto, Tom; Coebergh, Jan Willem; Aarts, Mieke J; Struikmans, Henk

    2017-07-15

    To investigate whether the Geriatric 8 (G8) and the Timed Get Up and Go Test (TGUGT) and clinical and demographic patient characteristics were associated with acute toxicity of radiation therapy and noncompliance in elderly cancer patients being irradiated with curative intent. Patients were eligible if aged ≥65 years and diagnosed with breast, non-small cell lung, prostate, head and neck, rectal, or esophageal cancer, and were referred for curative radiation therapy. We recorded acute toxicity and noncompliance and identified potential predictors, including the G8 and TGUGT. We investigated 402 patients with a median age of 72 years (range, 65-96 years). According to the G8, 44.4% of the patients were frail. Toxicity grade ≥3 was observed in 22% of patients who were frail according to the G8 and 9.1% of patients who were not frail. The difference was 13% (confidence interval 5.2%-20%; P=.0006). According to the TGUGT 18.8% of the patients were frail; 21% of the frail according to the TGUGT developed toxicity grade ≥3, compared with 13% who were not frail. The difference was 7.3% (confidence interval -2.7% to 17%; P=.11). Overall compliance was 95%. Toxicity was most strongly associated with type of primary tumor, chemotherapy, age, and World Health Organization performance status. Compliance was associated with type of primary tumor and age. The usefulness of the TGUGT and G8 score in daily practice seems to be limited. Type of primary tumor, chemoradiotherapy, age, and World Health Organization performance status were more strongly associated with acute toxicity. Only chemoradiotherapy and age were associated with noncompliance. Overall the compliance was very high. To allow better-informed treatment decisions, a more accurate prediction of toxicity is desirable. Copyright © 2017. Published by Elsevier Inc.

  6. Tissue-specific effects of acute aluminium exposure on the radiation-induced bystander effect in rainbow trout (Oncorhynchus mykiss, Walbaum).

    Science.gov (United States)

    Smith, Richard W; Seymour, Colin B; Moccia, Richard D; Mothersill, Carmel E

    2015-01-01

    To investigate if aluminium (Al) modifies the rainbow trout response to radiation exposure and/or the induction of a radiation-induced bystander effect. Rainbow trout were exposed to 100 or 200 μg l(-1) Al (for 3 h), a 0.5 Gy X-ray dose or Al followed immediately by irradiation. The exposed fish were then swum with completely untreated bystander fish. A human reporter cell clonogenic assay was used to determine whether Al exposure modified the effects of irradiation on the skin and gills from directly exposed fish and also the radiation-induced bystander effect in untreated fish. Al exposure did not modify the response to direct irradiation by the skin, or the gill. Al did not modify the bystander effect in the skin. However Al did modify the bystander effect in the gill. Gills of bystander fish swum with fish exposed to 200 μg l(-1) Al, followed by irradiation, caused a greater reduction in HPV-G cell survival than was caused by irradiation only. Interestingly Al exposure only also caused a bystander effect (reduced HPV-G survival) in the gill. This study shows that, in a multiple stressor scenario, the communication of radiation-induced stress signals is modified on a tissue-specific basis by acute Al exposure. Aside from the implications this has for radiological protection this response may also have potential for environmental monitoring where detection of the bystander effect could act as an indicator of radiation exposure when direct exposure responses are not evident.

  7. Low Dose Radiation Response Curves, Networks and Pathways in Human Lymphoblastoid Cells Exposed from 1 to 10 cGy of Acute Gamma Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Wyrobek, A. J.; Manohar, C. F.; Nelson, D. O.; Furtado, M. R.; Bhattacharya, M. S.; Marchetti, F.; Coleman, M.A.

    2011-04-18

    We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues. Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of {approx}80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, molecule transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.

  8. A prospective dosimetric and clinical comparison of acute hematological toxicities in three-dimensional conformal radiation therapy and intensity modulated radiation therapy with concurrent chemotherapy in carcinoma cervix

    Directory of Open Access Journals (Sweden)

    H U Avinash

    2015-01-01

    Full Text Available Background and Objectives: Acute hematological toxicities are an important cause of morbidity in patients receiving concurrent chemoradiation to pelvis in carcinoma cervix. The objective of this study was to evaluate the role of intensity-modulated radiotherapy (IMRT in reducing the dose to the bone marrow as compared with three-dimensional conformal radiotherapy (3DCRT and hence its impact on reducing the acute hematological toxicities. Materials and Methods: Eleven consecutive patients treated with IMRT and 12 patients treated with 3DCRT to the whole pelvis along with concurrent chemotherapy were selected. Bone marrow was delineated. V10 Gy, V20 Gy, V95%, and Dmean of bone marrow were recorded. Weekly blood counts were recorded and graded as per Common Terminology Criteria version 4.0 for all the patients. Results: The dose to the bone marrow V20 Gy was 206.78 ± 57.10 cc (75% and 251.70 ± 40.45 cc (91% for IMRT and 3DCRT, respectively (P = 0.04 and V95% was 23.30 ± 8.34% and 46.76 ± 6.71% for IMRT and 3DCRT, respectively (P = 0.001. The grade of toxicities during each week did not show the difference in either arm. However, the total count and Neutrophil counts during the 2nd week showed statistical significance between IMRT and 3DCRT. Conclusion: IMRT significantly reduces the dose to the bone marrow as compared to 3DCRT. The reduction of the dose did not translate into a decrease in acute hematological toxicities. Concurrent platinum-based chemotherapy is the probable cause for the hematological toxicities.

  9. Pneumonic Plague

    Science.gov (United States)

    ... Specific Hazards Bioterrorism A-Z Anthrax (Bacillus anthracis) Arenaviruses Treatment & Infection Control Specimen Submission & Lab Testing Education & ... hemorrhagic fevers (filoviruses [e.g., Ebola, Marburg] and arenaviruses [e.g., Lassa, Machupo]) Yersinia pestis (plague) Fact ...

  10. Hypersensitivity pneumonitis

    Science.gov (United States)

    ... often is not reversible. Eventually, end-stage lung disease and respiratory failure can occur. When to Contact a Medical ... Related MedlinePlus Health Topics Fungal Infections Interstitial Lung Diseases Molds Occupational Health Browse the Encyclopedia A.D.A.M., ...

  11. Therapy-related myelodysplastic syndrome and acute myeloid leukemia following chemotherapy (paclitaxel and carboplatin) and radiation therapy in ovarian cancer: a case report.

    Science.gov (United States)

    Ishikawa, M; Nakayama, K; Rahman, M T; Rahman, M; Katagiri, H; Katagiri, A; Ishibashi, T; Iida, K; Nakayama, N; Miyazaki, K

    2014-01-01

    In recent years, the incidence of therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML) that occur during chemotherapy for ovarian cancer has increased. While alkylating agents and topoisomerase II inhibitors are particularly mutagenic and have strong leukemogenic potential, paclitaxel and combination chemotherapy/radiation therapy also appear to induce t-MDS. The present authors report a case of t-MDS that developed during chemotherapy and radiation therapy for ovarian cancer. The patient was a 75-year-old woman who received six courses of cyclophosphamide/doxorubicin/cisplatin (CAP) therapy after initial surgery for Stage IIIc grade ovarian cancer in 1995. Beginning in February 2005, the patient experienced multiple recurrences due to sternal metastasis. Chemotherapy, including paclitaxel and carboplatin (TC), was administered intermittently and was combined with radiation therapy to a sternal metastatic lesion. Pancytopenia was observed in December 2008, and she was diagnosed with t-MDS (WHO subtype, refractory cytopenias with multilineage dysplasia [RCMD]): the time from first chemotherapy to t-MDS onset was 106 months. Without evidence of blast crisis, the recurrent lesions continued to grow and caused multiple cerebral infarctions, from which she eventually died. The cumulative doses of paclitaxel and carboplatin administered to this patient were 1,968 mg and 6,480 mg, respectively.

  12. Live cell detection of chromosome 2 deletion and Sfpi1/PU1 loss in radiation-induced mouse acute myeloid leukaemia.

    Science.gov (United States)

    Olme, C-H; Finnon, R; Brown, N; Kabacik, S; Bouffler, S D; Badie, C

    2013-10-01

    The CBA/H mouse model of radiation-induced acute myeloid leukaemia (rAML) has been studied for decades to bring to light the molecular mechanisms associated with multistage carcinogenesis. A specific interstitial deletion of chromosome 2 found in a high proportion of rAML is recognised as the initiating event. The deletion leads to the loss of Sfpi, a gene essential for haematopoietic development. Its product, the transcription factor PU.1 acts as a tumour suppressor in this model. Although the deletion can be detected early following ionising radiation exposure by cytogenetic techniques, precise characterisation of the haematopoietic cells carrying the deletion and the study of their fate in vivo cannot be achieved. Here, using a genetically engineered C57BL/6 mouse model expressing the GFP fluorescent molecule under the control of the Sfpi1 promoter, which we have bred onto the rAML-susceptible CBA/H strain, we demonstrate that GFP expression did not interfere with X-ray induced leukaemia incidence and that GFP fluorescence in live leukaemic cells is a surrogate marker of radiation-induced chromosome 2 deletions with or without point mutations on the remaining allele of the Sfpi1 gene. This study presents the first experimental evidence for the detection of this leukaemia initiating event in live leukemic cells.

  13. Discovery of a leptospirosis cluster amidst a pneumonic plague outbreak in a miners' camp in the Democratic Republic of the Congo.

    Science.gov (United States)

    Bertherat, Eric; Mueller, Melissa J; Shako, Jean-Christophe; Picardeau, Mathieu

    2014-02-07

    Conditions in the Democratic Republic of the Congo provide an ideal environment for leptospirosis and plague, both of which can cause severe pulmonary manifestations. In December 2004, an outbreak of lethal pneumonia occurred in a local mining camp, affecting 130 persons and killing 57 of them. Clinical signs, fast disease spread, and initial laboratory investigations suggested pneumonic plague. While leptospirosis had not recently been described in the region, it was considered as a differential diagnosis. Anti-Leptospira antibodies were detected by microscopic agglutination test (MAT). A confirmed case of leptospirosis was defined as having consistent clinical signs and any one of the following: seroconversion or four-fold increase in MAT titre for paired serum samples, or a MAT titre ≥ 1:400 for acute-phase serum samples. Twenty-nine of the 54 patients or convalescents tested for leptospirosis were seropositive. Two cases showed a confirmed infection for both plague and leptospirosis. While evidence supports the plague nature of this outbreak, the results suggest that some of the suspected plague cases might be due to leptospirosis. In any case, this diagnosis will have to be evoked in the future if a similar outbreak occurs in this region of Africa.

  14. Discovery of a Leptospirosis Cluster Amidst a Pneumonic Plague Outbreak in a Miners’ Camp in the Democratic Republic of the Congo

    Science.gov (United States)

    Bertherat, Eric; Mueller, Melissa J.; Shako, Jean-Christophe; Picardeau, Mathieu

    2014-01-01

    Conditions in the Democratic Republic of the Congo provide an ideal environment for leptospirosis and plague, both of which can cause severe pulmonary manifestations. In December 2004, an outbreak of lethal pneumonia occurred in a local mining camp, affecting 130 persons and killing 57 of them. Clinical signs, fast disease spread, and initial laboratory investigations suggested pneumonic plague. While leptospirosis had not recently been described in the region, it was considered as a differential diagnosis. Anti-Leptospira antibodies were detected by microscopic agglutination test (MAT). A confirmed case of leptospirosis was defined as having consistent clinical signs and any one of the following: seroconversion or four-fold increase in MAT titre for paired serum samples, or a MAT titre ≥ 1:400 for acute-phase serum samples. Twenty-nine of the 54 patients or convalescents tested for leptospirosis were seropositive. Two cases showed a confirmed infection for both plague and leptospirosis. While evidence supports the plague nature of this outbreak, the results suggest that some of the suspected plague cases might be due to leptospirosis. In any case, this diagnosis will have to be evoked in the future if a similar outbreak occurs in this region of Africa. PMID:24514425

  15. Neurobehavioural Changes and Brain Oxidative Stress Induced by Acute Exposure to GSM900 Mobile Phone Radiations in Zebrafish (Danio rerio)

    Science.gov (United States)

    Nirwane, Abhijit; Sridhar, Vinay; Majumdar, Anuradha

    2016-01-01

    The impact of mobile phone (MP) radiation on the brain is of specific interest to the scientific community and warrants investigations, as MP is held close to the head. Studies on humans and rodents revealed hazards MP radiation associated such as brain tumors, impairment in cognition, hearing etc. Melatonin (MT) is an important modulator of CNS functioning and is a neural antioxidant hormone. Zebrafish has emerged as a popular model organism for CNS studies. Herein, we evaluated the impact of GSM900MP (GSM900MP) radiation exposure daily for 1 hr for 14 days with the SAR of 1.34W/Kg on neurobehavioral and oxidative stress parameters in zebrafish. Our study revealed that, GSM900MP radiation exposure, significantly decreased time spent near social stimulus zone and increased total distance travelled, in social interaction test. In the novel tank dive test, the GSM900MP radiation exposure elicited anxiety as revealed by significantly increased time spent in bottom half; freezing bouts and duration and decreased distance travelled, average velocity, and number of entries to upper half of the tank. Exposed zebrafish spent less time in the novel arm of the Y-Maze, corroborating significant impairment in learning as compared to the control group. Exposure decreased superoxide dismutase (SOD), catalase (CAT) activities whereas, increased levels of reduced glutathione (GSH) and lipid peroxidation (LPO) was encountered showing compromised antioxidant defense. Treatment with MT significantly reversed the above neurobehavioral and oxidative derangements induced by GSM900MP radiation exposure. This study traced GSM900MP radiation exposure induced neurobehavioral aberrations and alterations in brain oxidative status. Furthermore, MT proved to be a promising therapeutic candidate in ameliorating such outcomes in zebrafish. PMID:27123163

  16. ACUTE AND CHRONIC INTAKES OF FALLOUT RADIONUCLIDES BY MARSHALLESE FROM NUCLEAR WEAPONS TESTING AT BIKINI AND ENEWETAK AND RELATED INTERNAL RADIATION DOSES

    Science.gov (United States)

    Simon, Steven L.; Bouville, André; Melo, Dunstana; Beck, Harold L.; Weinstock, Robert M.

    2014-01-01

    Annual internal radiation doses resulting from both acute and chronic intakes of all important dose-contributing radionuclides occurring in fallout from nuclear weapons testing at Bikini and Enewetak from 1946 through 1958 have been estimated for the residents living on all atolls and separate reef islands of the Marshall Islands. Internal radiation absorbed doses to the tissues most at risk to cancer induction (red bone marrow, thyroid, stomach, and colon) have been estimated for representative persons of all population communities for all birth years from 1929 through 1968, and for all years of exposure from 1948 through 1970. The acute intake estimates rely on a model using, as its basis, historical urine bioassay data, for members of the Rongelap Island and Ailinginae communities as well as for Rongerik residents. The model also utilizes fallout times of arrival and radionuclide deposition densities estimated for all tests and all atolls. Acute intakes of 63 radionuclides were estimated for the populations of the 20 inhabited atolls and for the communities that were relocated during the testing years for reasons of safety and decontamination. The model used for chronic intake estimates is based on reported whole-body, urine, and blood counting data for residents of Utrik and Rongelap. Dose conversion coefficients relating intake to organ absorbed dose were developed using internationally accepted models but specifically tailored for intakes of particulate fallout by consideration of literature-based evidence to choose the most appropriate alimentary tract absorption fraction (f1) values. Dose estimates were much higher for the thyroid gland than for red marrow, stomach wall, or colon. The highest thyroid doses to adults were about 7,600 mGy for the people exposed on Rongelap; thyroid doses to adults were much lower, by a factor of 100 or more, for the people exposed on the populated atolls of Kwajalein and Majuro. The estimates of radionuclide intake and

  17. Normal Tissue Complication Probability Analysis of Acute Gastrointestinal Toxicity in Cervical Cancer Patients Undergoing Intensity Modulated Radiation Therapy and Concurrent Cisplatin

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, Daniel R.; Song, William Y. [Center for Advanced Radiotherapy Technologies, Department of Radiation Oncology, University of California San Diego, La Jolla, CA (United States); Moiseenko, Vitali [Department of Medical Physics, Vancouver Cancer Centre, BC (Canada); Rose, Brent S.; Yashar, Catheryn M.; Mundt, Arno J. [Center for Advanced Radiotherapy Technologies, Department of Radiation Oncology, University of California San Diego, La Jolla, CA (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Center for Advanced Radiotherapy Technologies, Department of Radiation Oncology, University of California San Diego, La Jolla, CA (United States)

    2012-05-01

    Purpose: To test the hypothesis that increased bowel radiation dose is associated with acute gastrointestinal (GI) toxicity in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated radiation therapy (IMRT), using a previously derived normal tissue complication probability (NTCP) model. Methods: Fifty patients with Stage I-III cervical cancer undergoing IMRT and concurrent weekly cisplatin were analyzed. Acute GI toxicity was graded using the Radiation Therapy Oncology Group scale, excluding upper GI events. A logistic model was used to test correlations between acute GI toxicity and bowel dosimetric parameters. The primary objective was to test the association between Grade {>=}2 GI toxicity and the volume of bowel receiving {>=}45 Gy (V{sub 45}) using the logistic model. Results: Twenty-three patients (46%) had Grade {>=}2 GI toxicity. The mean (SD) V{sub 45} was 143 mL (99). The mean V{sub 45} values for patients with and without Grade {>=}2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V{sub 45} >150 mL. The proportion of patients with Grade {>=}2 GI toxicity with and without V{sub 45} >150 mL was 65% vs. 33% (p = 0.03). Logistic model parameter estimates V50 and {gamma} were 161 mL (95% confidence interval [CI] 60-399) and 0.31 (95% CI 0.04-0.63), respectively. On multivariable logistic regression, increased V{sub 45} was associated with an increased odds of Grade {>=}2 GI toxicity (odds ratio 2.19 per 100 mL, 95% CI 1.04-4.63, p = 0.04). Conclusions: Our results support the hypothesis that increasing bowel V{sub 45} is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V{sub 45} could reduce the risk of Grade {>=}2 GI toxicity by approximately 50% per 100 mL of bowel spared.

  18. Methotrexate-induced pneumonitis in Crohn's disease. Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    D'Andrea Nadia

    2010-10-01

    Full Text Available Abstract Methotrexate (MTX is a folate-antagonist used in several neoplastic and inflammatory diseases. Reports of pulmonary complications in patients given low-dose MTX therapy are increasing. Pulmonary toxicity from MTX has a variable frequency and can present with different forms. Most often MTX-induced pneumonia in patients affected by rheumatoid arthritis (RA is reported. In this paper we describe a case of MTX-related pneumonitis in a relatively young woman affected by Crohn's disease who presented non-productive cough, fever and dyspnea on exercise. Chest X-ray demonstrated bilateral interstitial infiltrates and at computed tomography (CT ground-glass opacities appeared in both lungs. At spirometry an obstructive defect was demonstrated. A rapid improvement of symptoms and the regression of radiographic and spirometric alterations was achieved through MTX withdrawal and the introduction of corticosteroid therapy.

  19. A case of interstitial pneumonitis in a patient with ulcerative colitis treated with azathioprine

    Institute of Scientific and Technical Information of China (English)

    Ferenc Nagy; Tamas Molnar; Eva Makula; Ildiko Kiss; Peter Milassin; Eva Zollei; Laszlo Tiszlavicz; Janos Lonovics

    2007-01-01

    The early hypersensitivity reaction and late bone marrow depression are well-known side-effects of azathioprine,whereas interstitial pneumonia is a rare complication.A 40-year old male patient had been treated with azathioprine in consequence of extensive ulcerative colitis for 10 years. He then complained of 7 d of fever,cough and catarrhal signs, without symptoms of active colitis. Opportunistic infections were ruled out. The chest X-ray, CT and lung biopsy demonstrated the presence of interstitial inflammation. Azathioprine therapy was discontinued as a potential source of the pulmonary infiltrate. In response to steroid therapy, and intensive care, the pulmonary infiltrate gradually decreased within 4 wk. Three months later, his ulcerative colitis relapsed,and ileo-anal pouch surgery was performed. In cases of atypical pneumonia, without a proven infection,azathioprine-associated interstitial pneumonitis may be present, which heals after withdrawal of the drug.

  20. Circumventing Y. pestis Virulence by Early Recruitment of Neutrophils to the Lungs during Pneumonic Plague.

    Directory of Open Access Journals (Sweden)

    Yaron Vagima

    2015-05-01

    Full Text Available Pneumonic plague is a fatal disease caused by Yersinia pestis that is associated with a delayed immune response in the lungs. Because neutrophils are the first immune cells recruited to sites of infection, we investigated the mechanisms responsible for their delayed homing to the lung. During the first 24 hr after pulmonary infection with a fully virulent Y. pestis strain, no significant changes were observed in the lungs in the levels of neutrophils infiltrate, expression of adhesion molecules, or the expression of the major neutrophil chemoattractants keratinocyte cell-derived chemokine (KC, macrophage inflammatory protein 2 (MIP-2 and granulocyte colony stimulating factor (G-CSF. In contrast, early induction of chemokines, rapid neutrophil infiltration and a reduced bacterial burden were observed in the lungs of mice infected with an avirulent Y. pestis strain. In vitro infection of lung-derived cell-lines with a YopJ mutant revealed the involvement of YopJ in the inhibition of chemoattractants expression. However, the recruitment of neutrophils to the lungs of mice infected with the mutant was still delayed and associated with rapid bacterial propagation and mortality. Interestingly, whereas KC, MIP-2 and G-CSF mRNA levels in the lungs were up-regulated early after infection with the mutant, their protein levels remained constant, suggesting that Y. pestis may employ additional mechanisms to suppress early chemoattractants induction in the lung. It therefore seems that prevention of the early influx of neutrophils to the lungs is of major importance for Y. pestis virulence. Indeed, pulmonary instillation of KC and MIP-2 to G-CSF-treated mice infected with Y. pestis led to rapid homing of neutrophils to the lung followed by a reduction in bacterial counts at 24 hr post-infection and improved survival rates. These observations shed new light on the virulence mechanisms of Y. pestis during pneumonic plague, and have implications for the

  1. Bioinformatics Methods for Learning Radiation-Induced Lung Inflammation from Heterogeneous Retrospective and Prospective Data

    OpenAIRE

    2009-01-01

    Radiotherapy outcomes are determined by complex interactions between physical and biological factors, reflecting both treatment conditions and underlying genetics. Recent advances in radiotherapy and biotechnology provide new opportunities and challenges for predicting radiation-induced toxicities, particularly radiation pneumonitis (RP), in lung cancer patients. In this work, we utilize datamining methods based on machine learning to build a predictive model of lung injury by retrospectiv...

  2. Anthocyanin-rich blueberry diets enhance protection of critical brain regions exposed to acute levels of 56Fe cosmic radiation

    Science.gov (United States)

    The protective effects of anthocyanin-rich blueberries on brain health are well documented and are particularly important under conditions of high oxidative stress which can lead to “accelerated aging”. One such scenario is exposure to space radiation, which consists of high-energy and -charge parti...

  3. Elevated ARG1 expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients.

    Science.gov (United States)

    Jung, Karen; Sabri, Siham; Hanson, John; Xu, Yaoxian; Wang, Ying Wayne; Lai, Raymond; Abdulkarim, Bassam S

    2015-01-01

    Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is associated with acute skin toxicities in at least 40% of treated patients. Monocyte-derived macrophages are polarized into functionally distinct (M1 or M2) activated phenotypes at injury sites by specific systemic cytokines known to play a key role in the transition between damage and repair in irradiated tissues. The role of M1 and M2 macrophages in RT-induced acute skin toxicities remains to be defined. We investigated the potential value of M1 and M2 macrophages as predictive factors of RT-induced skin toxicities in early breast cancer patients treated with adjuvant RT after lumpectomy. Blood samples collected from patients enrolled in a prospective clinical study (n = 49) were analyzed at baseline and after the first delivered 2Gy RT dose. We designed an ex vivo culture system to differentiate patient blood monocytes into macrophages and treated them with M1 or M2-inducing cytokines before quantitative analysis of their "M1/M2" activation markers, iNOS, Arg1, and TGFß1. Statistical analysis was performed to correlate experimental data to clinical assessment of acute skin toxicity using Common Toxicity Criteria (CTC) grade for objective evaluation of skin reactions. Increased ARG1 mRNA significantly correlated with higher grades of erythema, moist desquamation, and CTC grade. Multivariate analysis revealed that increased ARG1 expression in macrophages after a single RT dose was an independent prognostic factor of erythema (p = 0 .032), moist desquamation (p = 0 .027), and CTC grade (p = 0 .056). Interestingly, multivariate analysis of ARG1 mRNA expression in macrophages stimulated with IL-4 also revealed independent prognostic value for predicting acute RT-induced toxicity factors, erythema (p = 0 .069), moist desquamation (p = 0 .037), and CTC grade (p = 0 .046). To conclude, our findings underline for the first time the biological significance of increased ARG1 m

  4. Genetic Variants in CD44 and MAT1A Confer Susceptibility to Acute Skin Reaction in Breast Cancer Patients Undergoing Radiation Therapy.

    Science.gov (United States)

    Mumbrekar, Kamalesh Dattaram; Bola Sadashiva, Satish Rao; Kabekkodu, Shama Prasada; Fernandes, Donald Jerard; Vadhiraja, Bejadi Manjunath; Suga, Tomo; Shoji, Yoshimi; Nakayama, Fumiaki; Imai, Takashi; Satyamoorthy, Kapaettu

    2017-01-01

    Heterogeneity in radiation therapy (RT)-induced normal tissue toxicity is observed in 10% of cancer patients, limiting the therapeutic outcomes. In addition to treatment-related factors, normal tissue adverse reactions also manifest from genetic alterations in distinct pathways majorly involving DNA damage-repair genes, inflammatory cytokine genes, cell cycle regulation, and antioxidant response. Therefore, the common sequence variants in these radioresponsive genes might modify the severity of normal tissue toxicity, and the identification of the same could have clinical relevance as a predictive biomarker. The present study was conducted in a cohort of patients with breast cancer to evaluate the possible associations between genetic variants in radioresponsive genes described previously and the risk of developing RT-induced acute skin adverse reactions. We tested 22 genetic variants reported in 18 genes (ie, NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A, TGFβR3, MAD2L2, MAP3K7, MAT1A, RPS6KB2, ZNF830, SH3GL1, BAX, and XRCC1) using TaqMan assay-based real-time polymerase chain reaction. At the end of RT, the severity of skin damage was scored, and the subjects were dichotomized as nonoverresponders (Radiation Therapy Oncology Group grade skin reactions. Generalized multifactor dimensionality reduction analysis showed significant (P=.0107) gene-gene interactions between MAT1A and CD44. Furthermore, an increase in the total number of risk alleles was associated with increasing occurrence of overresponses (P=.0302). The genetic polymorphisms in radioresponsive genes act as genetic modifiers of acute normal tissue toxicity outcomes after RT by acting individually (rs8193), by gene-gene interactions (MAT1A and CD44), and/or by the additive effects of risk alleles. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Acute exposure to 930 MHz CW electromagnetic radiation in vitro affects reactive oxygen species level in rat lymphocytes treated by iron ions.

    Science.gov (United States)

    Zmyślony, Marek; Politanski, Piotr; Rajkowska, Elzbieta; Szymczak, Wieslaw; Jajte, Jolanta

    2004-07-01

    The aim of this study was to test the hypothesis that the 930 MHz continuous wave (CW) electromagnetic field, which is the carrier of signals emitted by cellular phones, affects the reactive oxygen species (ROS) level in living cells. Rat lymphocytes were used in the experiments. A portion of the lymphocytes was treated with iron ions to induce oxidative processes. Exposures to electromagnetic radiation (power density 5 W/m2, theoretical calculated SAR = 1.5 W/kg) were performed within a GTEM cell. Intracellular ROS were measured by the fluorescent probe dichlorofluorescin diacetate (DCF-DA). The results show that acute (5 and 15 min) exposure does not affect the number of produced ROS. If, however, FeCl2 with final concentration 10 microg/ml was added to the lymphocyte suspensions to stimulate ROS production, after both durations of exposure, the magnitude of fluorescence (ROS level during the experiment) was significantly greater in the exposed lymphocytes. The character of the changes in the number of free radicals observed in our experiments was qualitatively compatible with the theoretical prediction from the model of electromagnetic radiation effect on radical pairs.

  6. Prediction of Acute Radiation Mucositis using an Oral Mucosal Dose Surface Model in Carbon Ion Radiotherapy for Head and Neck Tumors.

    Directory of Open Access Journals (Sweden)

    Atsushi Musha

    Full Text Available To evaluate the dose-response relationship for development of acute radiation mucositis (ARM using an oral mucosal dose surface model (OMDS-model in carbon ion radiotherapy (C-ion RT for head and neck tumors.Thirty-nine patients receiving C-ion RT for head and neck cancer were evaluated for ARM (once per week for 6 weeks according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4.0, and the Radiation Therapy Oncology Group (RTOG scoring systems. The irradiation schedule typically used was 64 Gy [relative biological effectiveness (RBE] in 16 fractions for 4 weeks. Maximum point doses in the palate and tongue were compared with ARM in each patient.The location of the ARM coincided with the high-dose area in the OMDS-model. There was a clear dose-response relationship between maximum point dose and ARM grade assessed using the RTOG criteria but not the CTCAE. The threshold doses for grade 2-3 ARM in the palate and tongue were 43.0 Gy(RBE and 54.3 Gy(RBE, respectively.The OMDS-model was useful for predicting the location and severity of ARM. Maximum point doses in the model correlated well with grade 2-3 ARM.

  7. The Problem of the Mechanism of Action of Pyridoxine (Vitamin B6) in Acute Radiation Injury USSR.

    Science.gov (United States)

    2007-11-02

    eantradietory. Sossa autho?» «ässiday pyridoxin ® th« bait tharapauiie agast ie radiation «ie&nag« (27, 30); othare assert that thi« pffep&rstioa... pyridoxin « an« dlssadrel <ha?iag.th« aoute period of radiation •iQletM«» i»r«**«l th* aurrt val «ta öf tha rat« to 71 .3 par««* (*f tha 80 rate 57...IB the irradiated rabbit« which ha* ba«ss givan pyridoxine or bistamin« for a vaak befer® tha irradiation tha’■ eastajst of Mstasisa*« iß the bleed

  8. DNA Double-Strand Break Analysis by {gamma}-H2AX Foci: A Useful Method for Determining the Overreactors to Radiation-Induced Acute Reactions Among Head-and-Neck Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Goutham, Hassan Venkatesh; Mumbrekar, Kamalesh Dattaram [Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal, Karnataka (India); Vadhiraja, Bejadi Manjunath [Manipal Hospital, Bangalore, Karnataka (India); Fernandes, Donald Jerard; Sharan, Krishna [Department of Radiotherapy and Oncology, Shiridi Sai Baba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka (India); Kanive Parashiva, Guruprasad; Kapaettu, Satyamoorthy [Division of Biotechnology, Manipal Life Sciences Centre, Manipal University, Manipal, Karnataka (India); Bola Sadashiva, Satish Rao, E-mail: satishraomlsc@gmail.com [Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal, Karnataka (India)

    2012-12-01

    Purpose: Interindividual variability in normal tissue toxicity during radiation therapy is a limiting factor for successful treatment. Predicting the risk of developing acute reactions before initiation of radiation therapy may have the benefit of opting for altered radiation therapy regimens to achieve minimal adverse effects with improved tumor cure. Methods and Materials: DNA double-strand break (DSB) induction and its repair kinetics in lymphocytes of head-and-neck cancer patients undergoing chemoradiation therapy was analyzed by counting {gamma}-H2AX foci, neutral comet assay, and a modified version of neutral filter elution assay. Acute normal tissue reactions were assessed by Radiation Therapy Oncology Group criteria. Results: The correlation between residual DSBs and the severity of acute reactions demonstrated that residual {gamma}-H2AX foci in head-and-neck cancer patients increased with the severity of oral mucositis and skin reaction. Conclusions: Our results suggest that {gamma}-H2AX analysis may have predictive implications for identifying the overreactors to mucositis and skin reactions among head-and-neck cancer patients prior to initiation of radiation therapy.

  9. Cytokine profile of conditioned medium from human tumor cell lines after acute and fractionated doses of gamma radiation and its effect on survival of bystander tumor cells.

    Science.gov (United States)

    Desai, Sejal; Kumar, Amit; Laskar, S; Pandey, B N

    2013-01-01

    Cytokines are known to play pivotal roles in cancer initiation, progression and pathogenesis. Accumulating evidences suggest differences in basal and stress-induced cytokine profiles of cancers with diverse origin. However, a comprehensive investigation characterising the cytokine profile of various tumor types after acute and fractionated doses of gamma-irradiation, and its effect on survival of bystander cells is not well known in literature. In the present study, we have evaluated the cytokine secretion profile of human tumor cell lines (HT1080, U373MG, HT29, A549 and MCF-7) either before (basal) or after acute (2, 6 Gy) and fractionated doses (3×2 Gy) of gamma-irradiation in culture medium obtained from these cells by multiplex bead array/ELISA. Moreover, clonogenic assays were performed to evaluate the effect of conditioned medium (CM) on the survival and growth of respective cells. Based on the screening of 28 analytes, our results showed that the basal profiles of these cell lines varied considerably in terms of the number and magnitude of secreted factors, which was minimum in MCF-7. Interestingly, TNF-α, IL-1β, PDGF-AA, TGF-β1, fractalkine, IL-8, VEGF and GCSF were found in CM of all the cell lines. However, secretion of certain cytokines was cell line-specific. Moreover, CM caused increase in clonogenic survival of respective tumor cells (in the order HT1080>U373MG>HT29>A549>MCF-7), which was correlated with the levels of IL-1β, IL-6, IL-8, GMCSF and VEGF in their CM. After irradiation, the levels of most of the cytokines increased markedly in a dose dependent manner. The fold change in cytokine levels was lower in irradiated conditioned medium (ICM) of tumor cells collected after fractionated than respective acute dose, except in MCF-7. Interestingly, amongst these cell lines, the radiation-induced fold increase in cytokine levels was maximum in ICM of A549 cells. Moreover, bystander A549 cells treated with respective ICM showed dose dependent

  10. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates.

    Directory of Open Access Journals (Sweden)

    Vadim I Krivokrysenko

    Full Text Available There are currently no approved medical radiation countermeasures (MRC to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care administered in a mitigative regimen, 1-48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01 absolute survival advantage of 40-60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05 effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters.

  11. Scenario of a dirty bomb in an urban environment and acute management of radiation poisoning and injuries.

    Science.gov (United States)

    Chin, F K C

    2007-10-01

    In the new security environment, there is a clear and present danger of terrorists using non-conventional weapons to inflict maximum psychological and economic damage on their targets. This article examines two scenarios of radiation contamination and injury, one accidental in nature leading to environmental contamination, and another of deliberate intent resulting in injury and death. This article also discusses the management of injury from radiological dispersion devices or dirty bombs, with emphasis on the immediate aftermath as well as strategy recommendations.

  12. Changes in acute response to radiation after implementation of new national guidelines for head and neck cancer

    DEFF Research Database (Denmark)

    Hansen, C. R.; Bertelsen, Anders; Zukauskaite, R.

    2015-01-01

    for simple glottic tumours. Acute skin and mucosal reactions were scored weekly during RT, and 2 and 8 weeks after (0 none, 1 erythema, 2 dry desquamation/patchy mucositis, 3 wet desquamation/confluent mucositis, 4 ulceration). Use of analgesics was recorded equivalently on a 5-point scale. Clinical......Purpose/Objective: New national guidelines (GL) for radiotherapy (RT) of head and neck cancer (HNC) were implemented at the beginning of 2013. One purpose of the new GL was to nationally standardise the expansion from GTV to high risk CTV (CTV1). This standardisation has resulted in change...

  13. Primary case of human pneumonic plague occurring in a Himalayan marmot natural focus area Gansu Province, China

    Directory of Open Access Journals (Sweden)

    Pengfei Ge

    2015-04-01

    Full Text Available A case of primary pneumonic plague (PPP caused by Yersinia pestis is reported. This case occurred in the largest plague area in China. The patient died after contact with a dog that had captured an infected marmot. Three of 151 contacts were shown to be positive for antibody against F1 antigen by indirect hemagglutination assay, but none had clinical symptoms. There was no secondary case.

  14. Primary case of human pneumonic plague occurring in a Himalayan marmot natural focus area Gansu Province, China.

    Science.gov (United States)

    Ge, Pengfei; Xi, Jinxiao; Ding, Jun; Jin, Fachang; Zhang, Hong; Guo, Limin; Zhang, Jie; Li, Junlin; Gan, Zhiqiang; Wu, Bin; Liang, Junrong; Wang, Xin; Wang, Xinhua

    2015-04-01

    A case of primary pneumonic plague (PPP) caused by Yersinia pestis is reported. This case occurred in the largest plague area in China. The patient died after contact with a dog that had captured an infected marmot. Three of 151 contacts were shown to be positive for antibody against F1 antigen by indirect hemagglutination assay, but none had clinical symptoms. There was no secondary case.

  15. Acute and subacute idiopathic interstitial pneumonias.

    Science.gov (United States)

    Taniguchi, Hiroyuki; Kondoh, Yasuhiro

    2016-07-01

    Idiopathic interstitial pneumonias (IIPs) may have an acute or subacute presentation, or acute exacerbation may occur in a previously subclinical or unrecognized chronic IIP. Acute or subacute IIPs include acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), nonspecific interstitial pneumonia (NSIP), acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) and AE-NSIP. Interstitial lung diseases (ILDs) including connective tissue disease (CTD) associated ILD, hypersensitivity pneumonitis, acute eosinophilic pneumonia, drug-induced lung disease and diffuse alveolar haemorrhage need to be differentiated from acute and subacute IIPs. Despite the severe lack of randomized controlled trials for the treatment of acute and subacute IIPs, the mainstream treatment remains corticosteroid therapy. Other potential therapies reported in the literature include corticosteroids and immunosuppression, antibiotics, anticoagulants, neutrophil elastase inhibitor, autoantibody-targeted treatment, antifibrotics and hemoperfusion therapy. With regard to mechanical ventilation, patients in recent studies with acute and subacute IIPs have shown better survival than those in previous studies. Therefore, a careful value-laden decision about the indications for endotracheal intubation should be made for each patient. Noninvasive ventilation may be beneficial to reduce ventilator associated pneumonia.

  16. Acute exacerbations of fibrotic interstitial lung disease.

    Science.gov (United States)

    Churg, Andrew; Wright, Joanne L; Tazelaar, Henry D

    2011-03-01

    An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre-existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non-specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high-dose steroid therapy.

  17. Interstitial pneumonitis in patients with systemic sclerosis. Analysis by chest x-ray high-resolution computed tomography (HRCT)

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kana [Toho Univ., Tokyo (Japan). School of Medicine

    1999-01-01

    Systemic sclerosis (SSc) is a severe systemic collagen vascular disease of unknown cause characterized by marked vascular and connective tissue abnormalities in the skin and other organs. The lungs are frequently involved in patients with SSc, and pulmonary disease continues to be a significant cause of morbidity and mortality. High-resolution computed tomography (HRCT) is a sensitive technique potentially useful in detecting occult interstitial lung disease in patients with SSc. In the present study, chest X-ray HRCT findings were analyzed in 26 SSc patients in order to identify the characteristic morphological changes of interstitial pneumonitis in SSc patients. Interstitial pneumonitis was found in 21 patients (81%) with SSc. Chest X-ray CT findings in SSc patients were quite uniform and were characterized by sharply bordering dense attenuation and the predominance of ring-like lesions. Main lesions were located in the lower and posterior lung fields in a peripheral lobular pattern. There was no correlation between the extent of the interstitial lung disease and the duration from onset of SSc. In conclusion, it was found that, in patients with SSc, interstitial pneumonitis can be identified by characteristic chest X-ray CT findings. Furthermore, analysis of chest X-ray CT findings is useful in assessing the severity, clinical course and prognosis of patients with SSc. (author)

  18. [Three cases of hypersensitivity pneumonitis caused by inhalation of spores of Pholiota nameko and the background of the disease].

    Science.gov (United States)

    Konishi, K; Mouri, T; Kojima, Y; Chida, E; Sugawara, K; Abe, K; Bando, T; Ishii, M; Tamura, M

    1994-07-01

    Here we report a new type of hypersensitivity pneumonitis caused by inhalation of spores of Pholiota nameko. P. nameko is a kind of mushroom which is of Japanese delicacy. Among people who are working in nameko cultivation, we found three patients suffering from hypersensitivity pneumonitis, and identified that it was caused by inhalation of spores of P. nameko. Every patient was engaged in indoor nameko cultivation inside a building equipped with a air and moisture conditioning system for two to ten years. In the indoor environment, it was thought that they were exposed to and inhaled a high density of nameko spores. Among 15 healthy indoor nameko growers, we found 6 who had precipitating antibody against extracts from nameko spores; however, there were no antibody positive people in 17 outdoor nameko growers. As seen in dairy farmers, it was clarified that there is a percentage of precipitin positive nameko growers who are asymptomatic. This is concrete evidence that changes of mushroom cultivation style can induce a new type of hypersensitivity pneumonitis. These findings were considered to be an important experience from the view points of environmental pulmonary diseases and industrial medicine.

  19. Phase 2 study of idelalisib and entospletinib: pneumonitis limits combination therapy in relapsed refractory CLL and NHL.

    Science.gov (United States)

    Barr, Paul M; Saylors, Gene B; Spurgeon, Stephen E; Cheson, Bruce D; Greenwald, Daniel R; O'Brien, Susan M; Liem, Andre K D; Mclntyre, Rosemary E; Joshi, Adarsh; Abella-Dominicis, Esteban; Hawkins, Michael J; Reddy, Anita; Di Paolo, Julie; Lee, Hank; He, Joyce; Hu, Jing; Dreiling, Lyndah K; Friedberg, Jonathan W

    2016-05-19

    Although agents targeting B-cell receptor signaling have provided practice-changing results in relapsed chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), they require prolonged administration and provide incomplete responses. Given synergistic preclinical activity with phosphatidylinositol 3-kinase δ and spleen tyrosine kinase inhibition, this phase 2 study evaluated the safety and efficacy of the combination of idelalisib and entospletinib. Eligible patients with relapsed or refractory CLL or NHL underwent intrapatient dose escalation with each agent. With a median treatment exposure of 10 weeks, 60% and 36% of patients with CLL or follicular lymphoma, respectively, achieved objective responses. However, the study was terminated early because of treatment-emergent pneumonitis in 18% of patients (severe in 11 of 12 cases). Although most patients recovered with supportive measures and systemic steroids, 2 fatalities occurred and were attributed to treatment-emergent pneumonitis. Increases of interferon-γ and interleukins 6, 7, and 8 occurred over time in patients who developed pneumonitis. Future studies of novel combinations should employ conservative designs that incorporate pharmacodynamics/biomarker monitoring. These investigations should also prospectively evaluate plasma cytokine/chemokine levels in an attempt to validate biomarkers predictive of response and toxicity. This trial was registered at www.clinicaltrials.gov as #NCT01796470.

  20. microRNA Alterations Driving Acute and Late Stages of Radiation-Induced Fibrosis in a Murine Skin Model

    Energy Technology Data Exchange (ETDEWEB)

    Simone, Brittany A. [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Ly, David; Savage, Jason E. [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Hewitt, Stephen M. [Department of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Dan, Tu D. [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Ylaya, Kris [Department of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Shankavaram, Uma [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Lim, Meng; Jin, Lianjin [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Camphausen, Kevin [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Mitchell, James B. [Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Simone, Nicole L., E-mail: nicole.simone@jeffersonhospital.org [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States)

    2014-09-01

    Purpose: Although ionizing radiation is critical in treating cancer, radiation-induced fibrosis (RIF) can have a devastating impact on patients' quality of life. The molecular changes leading to radiation-induced fibrosis must be elucidated so that novel treatments can be designed. Methods and Materials: To determine whether microRNAs (miRs) could be responsible for RIF, the fibrotic process was induced in the right hind legs of 9-week old CH3 mice by a single-fraction dose of irradiation to 35 Gy, and the left leg served as an unirradiated control. Fibrosis was quantified by measurements of leg length compared with control leg length. By 120 days after irradiation, the irradiated legs were 20% (P=.013) shorter on average than were the control legs. Results: Tissue analysis was done on muscle, skin, and subcutaneous tissue from irradiated and control legs. Fibrosis was noted on both gross and histologic examination by use of a pentachrome stain. Microarrays were performed at various times after irradiation, including 7 days, 14 days, 50 days, 90 days, and 120 days after irradiation. miR-15a, miR-21, miR-30a, and miR-34a were the miRs with the most significant alteration by array with miR-34a, proving most significant on confirmation by reverse transcriptase polymerase chain reaction, c-Met, a known effector of fibrosis and downstream molecule of miR-34a, was evaluated by use of 2 cell lines: HCT116 and 1522. The cell lines were exposed to various stressors to induce miR changes, specifically ionizing radiation. Additionally, in vitro transfections with pre-miRs and anti-miRs confirmed the relationship of miR-34a and c-Met. Conclusions: Our data demonstrate an inverse relationship with miR-34a and c-Met; the upregulation of miR-34a in RIF causes inhibition of c-Met production. miRs may play a role in RIF; in particular, miR-34a should be investigated as a potential target to prevent or treat this devastating side effect of irradiation.

  1. Profiles and Time Course of Acute Radiation Toxicity Symptoms during Conformal Radiotherapy for Cancer of the Prostate

    Energy Technology Data Exchange (ETDEWEB)

    Hovdenak, Nils; Karlsdottir, Aasa; Soerbye, Halfdan; Dahl, Olav [Univ. of Bergen (Norway). Div. of Gastroenterology

    2003-11-01

    Symptoms of gastrointestinal toxicity are dose-limiting for pelvic radiotherapy (RT). Existing toxicity registrations (RTOG/EORTC) are helpful in defining maximal tolerated doses, but tend to underestimate the total toxicity burden by excluding several minor complaints. We have applied a more detailed and quantitative recording of symptoms and related these scores to RT-induced endoscopic and histopathologic changes. Prevalence and severity of specific toxicity symptoms were recorded before, during (weeks 2 and 6) and 2 and 8 weeks after RT in 96 patients undergoing external beam RT for localized prostate cancer. RTOG/EORTC acute toxicity and ad hoc total toxicity scores (TTS) were recorded. TTS scores were calculated by adding scores based on visual analog scale (VAS) grading of individual symptoms. Fifty of the patients also underwent sequential proctoscopy with mucosal biopsy. Individual symptoms increased, but differed in prevalence and intensity during and after RT. TTS increased during the entire treatment course in spite of normalizing histopathologic and endoscopic changes from week 2 onwards. Twenty-seven patients had no RTOG/EORTC toxicity, four had grade 3 and none had grade 4 toxicity. All patients with grade 0 had increased TTS. Thus, TTS appeared more sensitive than RTOG/EORTC scoring. The study demonstrates that multiple toxicity symptoms contribute to total toxicity in response to pelvic RT. TTS is a feasible and sensitive method for detecting and quantifying acute toxicity and unveils morbidity which remains hidden with the RTOG/EORTC score system. The development and timing of symptoms may give clues to pathogenesis, treatment, and prophylaxis.

  2. Brief note and evaluation of acute-radiation syndrome and treatment of a Tokai-mura criticality accident patient

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, Takeshi; Futami, Satoru; Nishida, Masamichi; Suzuki, Toru; Sakamoto, Tetsuya; Suzuki, Norio; Maekawa, Kazuhiko [Tokyo Univ. (Japan). Graduate School of Medicine

    2001-09-01

    Patient A who was exposed to a critical dose of radiation developed skin lesions throughout the body surface, gastrointestinal disorder with massive diarrhea and prominent bleeding, which caused severe loss in body fluids. Gastrointestinal bleeding due to the deteriorated intestinal mucosa was considered to be one of the major causes of death, although infection did not develop, possibly because of SDD and aseptic intensive care, until terminal stages. Patient A ultimately developed respiratory and renal failure in addition to skin exudate and gastrointestinal bleeding, and died of multiple organ failure on the 83rd day after exposure. The extreme unevenness of the dose distribution and the neutron versus {gamma}-ray component made the clinical manifestation very complicated. Initially, the mean absorbed dose was calculated as 16-20 GyEq for Patient A, mainly based on neutron-activated {sup 24}Na in the blood. However, a very recent calculation showed that the absorbed skin dose was highest at the upper-right abdomen reaching 61.8 Gy (27.0 as neutron plus 34.8 Gy as {gamma}-ray). The dorsal side was calculated to have received one eighth of the value of the abdominal side, and much smaller neutron component. His absorbed-dose distribution throughout the body was very inhomogeneous because of the closeness of the standing point to the mixing tank. Despite prolonged survival because of intensive care with massive fluids and blood transfusion, peripheral blood stem-cell transplantation, cultured skin-cell grafts, and the administration of cytokines for marrow, the patient was not saved. Restoration of the bone marrow function, prevention of skin fibrosis, radiation lung damage, and repair of gastrointestinal mucosa, and final recovery of the patient were elusive. Abundant personnel and resources were also a prerequisite to allow for the comprehensive and collective intensive care. A further understanding of the effects of high-dose radiation as well as the basic and

  3. A familial history of pulmonary fibrosis in patients with chronic hypersensitivity pneumonitis.

    Science.gov (United States)

    Okamoto, Tsukasa; Miyazaki, Yasunari; Tomita, Makoto; Tamaoka, Meiyo; Inase, Naohiko

    2013-01-01

    Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease induced by the inhalation of a variety of antigens. Patients with chronic HP often have a family history of pulmonary fibrosis. This strongly suggests that both genetic and environmental factors play an important role in the pathogenesis of chronic HP. We aimed to investigate the epidemiology and clinical features of chronic HP patients with a family history of pulmonary fibrosis. We retrospectively reviewed the clinical information of 114 cases diagnosed with chronic HP with insidious onset between 1992 and 2009. Twenty cases (17.5%) were identified as having a family history of pulmonary fibrosis. All of these patients had lived apart from their afflicted relatives for at least several decades. The familial cases were younger than the nonfamilial cases at onset (57.5 ± 9.6 vs. 64.0 ± 7.0 years old, p = 0.008). The predicted vital capacity percentage and partial pressure of oxygen in arterial blood gas were significantly higher in the familial cases. There were no differences between the 2 groups in gender, smoking history, bronchoalveolar lavage fluid profile, radiologic findings or other clinical features. We found a familial clustering in patients with chronic HP. Various factors including genetic susceptibility to pulmonary fibrosis and environmental factors may contribute to the development of familial chronic HP. Copyright © 2012 S. Karger AG, Basel.

  4. Chronic hypersensitivity pneumonitis: identification of key prognostic determinants using automated CT analysis.

    Science.gov (United States)

    Jacob, Joseph; Bartholmai, Brian J; Egashira, Ryoko; Brun, Anne Laure; Rajagopalan, Srinivasan; Karwoski, Ronald; Kokosi, Maria; Hansell, David M; Wells, Athol U

    2017-05-04

    Chronic hypersensitivity pneumonitis (CHP) has a variable disease course. Computer analysis of CT features was used to identify a subset of CHP patients with an outcome similar to patients with idiopathic pulmonary fibrosis (IPF). Consecutive patients with a multi-disciplinary team diagnosis of CHP (n = 116) had pulmonary function tests (FEV1, FVC, DLco, Kco, and a composite physiologic index [CPI]) and CT variables predictive of mortality evaluated by analysing visual and computer-based (CALIPER) parenchymal features: total interstitial lung disease (ILD) extent, honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume (PVV), emphysema, and traction bronchiectasis. Mean survival was compared between both CHP and IPF patients (n = 185). In CHP, visual/CALIPER measures of reticular pattern, honeycombing, visual traction bronchiectasis, and CALIPER ILD extent were predictive of mortality (p CHP patients with a PVV threshold >6 · 5% of the lung had a mean survival (35 · 3 ± 6 · 1 months; n = 20/116 [17%]) and rate of disease progression that closely matched IPF patients (38 · 4 ± 2 · 2 months; n = 185). Pulmonary vessel volume can identify CHP patients at risk of aggressive disease and a poor IPF-like prognosis.

  5. The value of family history in the diagnosis of hypersensitivity pneumonitis in children

    Directory of Open Access Journals (Sweden)

    Joana Cardoso

    2014-04-01

    Full Text Available Hypersensitivity pneumonitis (HP, or extrinsic allergic alveolitis, is an immunologically mediated disease resulting from the inhalation of organic substances that trigger an inflammatory response in the alveolar wall, bronchioles, and interstitium in susceptible individuals. Although HP is predominantly an occupational disease, seen in adulthood, cases in children have been described. The diagnosis of HP requires a high degree of suspicion. The treatment consists in avoiding contact with the antigen, and, in some cases, systemic corticosteroids might be necessary in order to prevent its progression to pulmonary fibrosis. We report the clinical cases of three children with a history of contact with birds and a family history of HP. All three patients presented with cough and dyspnea on exertion. The disease was diagnosed on the basis of the clinical history and ancillary diagnostic test results consistent with the diagnosis, including a predominance of lymphocytes (> 60%, CD8+ T lymphocytes in particular in bronchoalveolar lavage fluid and a ground-glass pattern seen on HRCT of the chest. Early diagnosis is crucial in order to prevent HP from progressing to pulmonary fibrosis. Hereditary factors seem to influence the onset of the disease.

  6. CXCR3/CXCL10 interactions in the development of hypersensitivity pneumonitis

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    Zambello Renato

    2005-02-01

    Full Text Available Abstract Background Hypersensitivity pneumonitis (HP is an interstitial lung disease caused by repeated inhalations of finely dispersed organic particles or low molecular weight chemicals. The disease is characterized by an alveolitis sustained by CD8(+ cytotoxic T lymphocytes, granuloma formation, and, whenever antigenic exposition continues, fibrosis. Although it is known that T-cell migration into the lungs is crucial in HP reaction, mechanisms implicated in this process remain undefined. Methods Using flow cytometry, immunohistochemistry, confocal microscopy analysis and chemotaxis assays we evaluated whether CXCL10 and its receptor CXCR3 regulate the trafficking of CD8(+ T cells in HP lung. Results Our data demonstrated that lymphocytes infiltrating lung biopsies are CD8 T cells which strongly stain for CXCR3. However, T cells accumulating in the BAL of HP were CXCR3(+/IFNγ(+ Tc1 cells exhibiting a strong in vitro migratory capability in response to CXCL10. Alveolar macrophages expressed and secreted, in response to IFN-γ, definite levels of CXCL10 capable of inducing chemotaxis of the CXCR3(+ T-cell line. Interestingly, striking levels of CXCR3 ligands could be demonstrated in the fluid component of the BAL in individuals with HP. Conclusion These data indicate that IFN-γ mediates the recruitment of lymphocytes into the lung via production of the chemokine CXCL10, resulting in Tc1-cell alveolitis and granuloma formation.

  7. The isolation of multiple strains of Mycoplasma ovipneumoniae from individual pneumonic sheep lungs.

    Science.gov (United States)

    Ionas, G; Clarke, J K; Marshall, R B

    1991-11-01

    The heterogeneity of Mycoplasma ovipneumoniae isolates from the lungs of sheep with chronic non-progressive pneumonia (CNP) from the same flock raised the possibility that multiple isolates derived from one lung were not all identical. To test this hypothesis, thirty isolates were obtained from each of six pneumonic sheep lungs at slaughter. Four lungs had relatively severe lesions and from each of these, three or four strains of M. ovipneumonia, distinguishable by REA and in most cases by SDS-PAGE, were detected. From the lungs of each of two sheep with mild lesions, two strains of M. ovipneumoniae were detected. Four isolates from one lung were further examined by restriction endonuclease analysis (REA) using many restriction endonucleases. Those which differed with EcoRI also differed when other restriction endonucleases were used. However, partial digests occurred mainly with those restriction endonucleases which recognise cytosine-rich sequences. The presence of multiple strains of one species of microorganism in individual lesions is an unusual concept which may not be limited to one disease or to one host.

  8. Chest radiographic features of lymphocytic interstitial pneumonitis in HIV-infected children

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    Pitcher, R.D., E-mail: pitcher@iafrica.co [Division of Paediatric Radiology, Red Cross War Memorial Children' s Hospital, Department of Radiation Medicine, University of Cape Town (South Africa); Beningfield, S.J. [Division of Radiology, New Groote Schuur Hospital and University of Cape Town (South Africa); Zar, H.J. [Department of Paediatric Pulmonology, Red Cross War Memorial Children' s Hospital, School of Child and Adolescent Health, University of Cape Town (South Africa)

    2010-02-15

    Aim: To review the radiological features of biopsy-proven lymphocytic interstitial pneumonitis (LIP) in human immunodeficiency virus (HIV)-infected children and establish whether these are based on systematic radiological analysis, and to investigate whether more specific radiological diagnostic criteria can be developed. Materials and methods: A Medline search of English-language articles on the radiological features of biopsy-proven LIP in HIV-infected children was conducted for the period 1982 to 2007 inclusive. Radiological findings were compared with the Centers for Disease Control and Prevention (CDC) criteria for a presumptive diagnosis of LIP. Results: Pulmonary pathology was recorded as 'diffuse' and 'bilateral' in 125 (97.6%) of 128 reported cases of LIP. Twenty-five different terms were used to describe the pulmonary parenchyma. In 96 (75%), the terminology was consistent with CDC diagnostic criteria. Radiological evolution was documented in 43 (33.5%). Persistent focal opacification superimposed on diffuse pulmonary nodularity was demonstrated in 10 (7.8%). The method of radiological evaluation was described in six (4.6%). In no instance was the terminology defined. Conclusion: The radiological features of LIP have not been systematically analysed. However, CDC criteria remain reliable, allowing diagnosis of at least 75% of cases. The sensitivity of these criteria may be increased by including cases with persistent focal pulmonary opacification superimposed on diffuse nodularity. Longitudinal studies utilizing standardized radiographic analysis are needed to elucidate the natural history of LIP.

  9. Treatment of acute radiodermatitis with an oil-in-water emulsion following radiation therapy for breast cancer. A controlled, randomized trial

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    Jensen, Jens-Michael; Gau, Tanja; Foelster-Holst, Regina; Proksch, Ehrhardt [Kiel Univ. (Germany). Dept. of Dermatology; Schultze, Juergen [Kiel Univ. (Germany). Dept. of Therapeutic Radiology; Lemmnitz, Gunter; Abels, Christoph [Dr. August Wolff GmbH und Co. KG Arzneimittel, Bielefeld (Germany); May, Theodor [Gesellschaft fuer Biometrie und Psychometrie GbR, Bielefeld (Germany)

    2011-06-15

    A side effect of radiotherapy for breast cancer is acute radiodermatitis. It is a common practice to keep irradiated skin dry on account of data from the 1950s that suggested this regimen limits dermatitis. However, severe dryness of the skin induced by irradiation results in itching and discomfort. Dry skin is characterized by scaliness, epidermal barrier dysfunction, and reduced stratum corneum hydration, and these signs and symptoms are reduced by treatment with an emulsion. We performed a randomized, controlled, open-label study with 66 patients (ITT population), treating the irradiated skin in one group (n = 34) with an oil-in-water emulsion (WO1932), while leaving the other group untreated (n = 32). Clinical scoring (ONS radiation skin reaction scoring, pruritus) and biophysical measurements (stratum corneum hydration and transepidermal water loss (TEWL), as a marker of skin barrier function) were determined at day 1 (directly after termination of the radiation therapy), day 8, and day 47 ({+-} 7). Irradiation increased the ONS score and pruritus, whereas skin hydration and TEWL were reduced. The primary hypothesis that the increase in skin hydration was significantly greater in the emulsion-treated compared to the untreated group as early as after 8 days of treatment could not be confirmed. At the end of the study (day 47 {+-} 7), however, normalization of stratum corneum hydration was more advanced in the treatment group compared to the untreated group and nearly reached the values of the contralateral healthy breast skin. ONS score and pruritus also revealed an advantage for the emulsion-treated group. TEWL did not show significant changes during emulsion treatment. No adverse events were caused by the treatment regimens. Treatment of radiodermatitis with an oil-in-water emulsion was well tolerated, enhanced stratum corneum hydration, improved clinical indicators, and provided relief from itching. (orig.)

  10. Modeling the Risk of Radiation-Induced Acute Esophagitis for Combined Washington University and RTOG Trial 93-11 Lung Cancer Patients

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    Huang, Ellen X.; Bradley, Jeffrey D.; El Naqa, Issam [Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO (United States); Hope, Andrew J.; Lindsay, Patricia E. [Princess Margaret Hospital, Toronto, ON (Canada); Bosch, Walter R.; Matthews, John W. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO (United States); Sause, William T. [Department of Radiation Oncology, LDS Hospital, Salt Lake City, UT (United States); Graham, Mary V. [Department of Radiation Oncology, Phelps County Regional Hospital, Rolla, MO (United States); Deasy, Joseph O., E-mail: deasyj@mskcc.org [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-04-01

    Purpose: To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non-small-cell lung cancer. Methods and Materials: The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemotherapy, fraction size). A wide range of dose-volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUD (generalized equivalent uniform dose) values. Results: The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior-inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 Asterisk-Operator MED+1.50 Asterisk-Operator ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001). Conclusions: Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts

  11. Effect of a prostaglandin - given rectally for prevention of radiation-induced acute proctitis - on late rectal toxicity. Results of phase III randomized, placebo-controlled, double-blind study

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    Kertesz, Tereza; Herrmann, Markus K.A.; Christiansen, Hans; Hermann, Robert M.; Hess, Clemens F.; Hille, Andrea [Dept. of Radiotherapy and Radiooncology, Univ. of Goettingen (Germany); Zapf, Antonia [Dept. of Medical Statistics, Univ. of Goettingen (Germany); Pradier, Olivier [Dept. of Radiotherapy and Radiooncology, Univ. of Brest (France); Schmidberger, Heinz [Dept. of Radiotherapy and Radiooncology, Univ. of Mainz (Germany)

    2009-09-15

    Background and purpose: to assess the late effect of a prostaglandin, given rectally during irradiation, on late rectal toxicity. In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol, however, significantly more rectal bleeding had been reported. Patients and methods: a total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale. Results: the median follow-up was 50 months. 20 patients suffered from grade 1, four patients from grade 2 as well, and three patients only from grade 2 toxicity. Frequency, bleeding and urgency were the most commonly reported symptoms. In keeping with other studies and clinical experience, the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity (p = 0.03). Any acute rectal bleeding was significant correlated with any late rectal bleeding (p = 0.017). Conclusion: misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no negative impact on the incidence and severity of late rectal bleeding, in contrast to acute rectal bleeding. The routine clinical use of misoprostol suppositories cannot be recommended. (orig.)

  12. Altered distribution of Pneumocystis carinii pneumonia during radiation therapy

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    Kim, H.H.; Park, S.H. [Department of Diagnostic Radiology, Kangnam St. Mary`s Hospital, College of Medicine, Seoul (Korea, Republic of); Kim, S.C. [Department of Internal Medicine, Kangnam St. Mary`s Hospital, College of Medicine, Catholic University of Korea, Seoul (Korea, Republic of); Kim, Y.S. [Department of Therapeutic Radiology, Kangnam St. Mary`s Hospital, College of Medicine, Catholic University of Korea, Seoul (Korea, Republic of)

    1999-10-01

    The radiographic findings of Pneumocystis carinii pneumonia (PCP) are various. The typical findings are diffuse, bilateral, symmetric, finely granular, or reticular infiltrates. In patients taking aerosol pentamidine, atypical findings may be the first manifestation. One interesting radiologic finding of PCP is that the pneumonia may spare the irradiated lung. We report PCP developed in a patient undergoing irradiation for lung cancer. High-resolution CT revealed diffuse, bilateral, and symmetric ground-glass opacities with septal thickening in both lungs; however, the radiation port was spared and appeared as the ``photographic negative of post-radiation pneumonia.`` The distribution of the pneumonic infiltrates was altered by radiotherapy. (orig.) With 1 fig., 6 refs.

  13. HemaMax™, a recombinant human interleukin-12, is a potent mitigator of acute radiation injury in mice and non-human primates.

    Directory of Open Access Journals (Sweden)

    Lena A Basile

    Full Text Available HemaMax, a recombinant human interleukin-12 (IL-12, is under development to address an unmet medical need for effective treatments against acute radiation syndrome due to radiological terrorism or accident when administered at least 24 hours after radiation exposure. This study investigated pharmacokinetics, pharmacodynamics, and efficacy of m-HemaMax (recombinant murine IL-12, and HemaMax to increase survival after total body irradiation (TBI in mice and rhesus monkeys, respectively, with no supportive care. In mice, m-HemaMax at an optimal 20 ng/mouse dose significantly increased percent survival and survival time when administered 24 hours after TBI between 8-9 Gy (p<0.05 Pearson's chi-square test. This survival benefit was accompanied by increases in plasma interferon-γ (IFN-γ and erythropoietin levels, recovery of femoral bone hematopoiesis characterized with the presence of IL-12 receptor β2 subunit-expressing myeloid progenitors, megakaryocytes, and osteoblasts. Mitigation of jejunal radiation damage was also examined. At allometrically equivalent doses, HemaMax showed similar pharmacokinetics in rhesus monkeys compared to m-HemaMax in mice, but more robustly increased plasma IFN-γ levels. HemaMax also increased plasma erythropoietin, IL-15, IL-18, and neopterin levels. At non-human primate doses pharmacologically equivalent to murine doses, HemaMax (100 ng/Kg and 250 ng/Kg administered at 24 hours after TBI (6.7 Gy/LD(50/30 significantly increased percent survival of HemaMax groups compared to vehicle (p<0.05 Pearson's chi-square test. This survival benefit was accompanied by a significantly higher leukocyte (neutrophils and lymphocytes, thrombocyte, and reticulocyte counts during nadir (days 12-14 and significantly less weight loss at day 12 compared to vehicle. These findings indicate successful interspecies dose conversion and provide proof of concept that HemaMax increases survival in irradiated rhesus monkeys by promoting

  14. Apoptotic resistance to ionizing radiation in pediatric B-precursor acute lymphoblastic leukemia frequently involves increased NF-kappaB survival pathway signaling.

    Science.gov (United States)

    Weston, Victoria J; Austen, Belinda; Wei, Wenbin; Marston, Eliot; Alvi, Azra; Lawson, Sarah; Darbyshire, Philip J; Griffiths, Mike; Hill, Frank; Mann, Jill R; Moss, Paul A H; Taylor, A Malcolm R; Stankovic, Tatjana

    2004-09-01

    To investigate possible causes of the variable response to treatment in pediatric B-precursor acute lymphoblastic leukemia (ALL) and to establish potential novel therapeutic targets, we used ionizing radiation (IR) exposure as a model of DNA damage formation to identify tumors with resistance to p53-dependent apoptosis. Twenty-one of 40 ALL tumors responded normally to IR, exhibiting accumulation of p53 and p21 proteins and cleavage of caspases 3, 7, and 9 and of PARP1. Nineteen tumors exhibited apoptotic resistance and lacked PARP1 and caspase cleavage; although 15 of these tumors had normal accumulation of p53 and p21 proteins, examples exhibited abnormal expression of TRAF5, TRAF6, and cIAP1 after IR, suggesting increased NF-kappaB prosurvival signaling as the mechanism of apoptotic resistance. The presence of a hyperactive PARP1 mutation in one tumor was consistent with such increased NF-kappaB activity. PARP1 inhibition restored p53-dependent apoptosis after IR in these leukemias by reducing NF-kappaB DNA binding and transcriptional activity. In the remaining 4 ALL tumors, apoptotic resistance was associated with a TP53 mutation or with defective activation of p53. We conclude that increased NF-kappaB prosurvival signaling is a frequent mechanism by which B-precursor ALL tumors develop apoptotic resistance to IR and that PARP1 inhibition may improve the DNA damage response of these leukemias.

  15. The influence of the combined effects of acute gamma-radiation, sodium bromate and sodium nitrate on lettuce (Lactuca sativa) seedling root growth

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    Pryakhin, E.; Osipov, D. [Urals Research Center for Radiation Medicine - URCRM (Russian Federation)

    2014-07-01

    Among special industrial reservoirs used for the storage of liquid radioactive waste of Mayak PA, Russia, one of the most radioactively contaminated is the R-17 reservoir, so-called 'Staroye Boloto' (the total β-activity of water ranged in the observation period from 0.4 MBq/l to 4.5 MBq/l, the total a-activity ranged from 43 to 420 Bq/l). Also this reservoir is characterized by high level of chemical contamination, in particular, the concentration of nitrates in water is 2.5-4,4 g/l, sodium bromate - up to 35 mg/l. One of the interesting questions is interaction of radiation and chemical contamination in their effect on living organisms in this reservoir. In laboratory experiments seeds of Lactuca sativa were used; the effect of the studied factor on the length of the sprout's root was estimated. To assess the effect of chemical toxicants the solutions of each salt in 7 different concentrations were used, distilled water was used as a control. For evaluation of acute effects of external gamma irradiation the seeds after exposure for 24 hours in distilled water, were irradiated at 7 different doses using gamma-unit on the basis of Cs-137 with the dose rate of 0.62 Gy/min. To assess the combined effects of acute external gamma irradiation, of nitrates and bromates, seeds after 24 hour exposure at each test concentration of the salts solutions were irradiated using gamma-unit. To calculate the effective concentrations or doses was used drc package for R software. To calculate the dose rate to aquatic organisms in the R-17 was used ERICA Assessment Tool 2012. It was found out that the EC50 of sodium nitrate for lettuce was 2.69 g/l, which is comparable to the concentration of nitrates in the 'Staroye Boloto'. This indicates that nitrate can have significant toxic effect on aquatic higher plants of the reservoir. The EC50 of sodium bromate was 14.6 mg/l. This is less than the maximum concentration of the substance in the R-17, which suggests

  16. Heart and radiation

    Directory of Open Access Journals (Sweden)

    Lauro Martins Júnior

    2011-12-01

    Full Text Available ABSTRATC The heart exposition to ionizing radiation may produce lesions in cardiac structures, acute (in most of cases benign and reversible, or months and even years later. There is a direct relationship of severity of lesions with radiation doses. The clinical picture receives a new denomination: radiation induced cardiopathy. The more frequent use of radiation in diagnosis and therapeutics increases the importance of their knowledge and especially their prevention.

  17. Development and testing of a rapid diagnostic test for bubonic and pneumonic plague.

    Science.gov (United States)

    Chanteau, Suzanne; Rahalison, Lila; Ralafiarisoa, Lalao; Foulon, Jeanine; Ratsitorahina, Mahery; Ratsifasoamanana, Lala; Carniel, Elisabeth; Nato, Farida

    2003-01-18

    Plague is often fatal without prompt and appropriate treatment. It affects mainly poor and remote populations. Late diagnosis is one of the major causes of human death and spread of the disease, since it limits the effectiveness of control measures. We aimed to develop and assess a rapid diagnostic test (RDT) for plague. We developed a test that used monoclonal antibodies to the F1 antigen of Yersinia pestis. Sensitivity and specificity were assessed with a range of bacterial cultures and clinical samples, and compared with findings from available ELISA and bacteriological tests for plague. Samples from patients thought to have plague were tested with the RDT in the laboratory and by health workers in 26 pilot sites in Madagascar. The RDT detected concentrations of F1 antigen as low as 0.5 ng/mL in up to 15 min, and had a shelf life of 21 days at 60 degrees C. Its sensitivity and specificity were both 100%. RDT detected 41.6% and 31% more positive clinical specimens than did bacteriological methods and ELISA, respectively. The agreement rate between tests done at remote centres and in the laboratory was 89.8%. With the combination of bacteriological methods and F1 ELISA as reference standard, the positive and negative predictive values of the RDT were 90.6% and 86.7%, respectively. Our RDT is a specific, sensitive, and reliable test that can easily be done by health workers at the patient's bedside, for the rapid diagnosis of pneumonic and bubonic plague. This test will be of key importance for the control of plague in endemic countries.

  18. Immunoglobulin free light chains are increased in hypersensitivity pneumonitis and idiopathic pulmonary fibrosis.

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    Tom Groot Kormelink

    Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis (IPF, a devastating lung disorder of unknown aetiology, and chronic hypersensitivity pneumonitis (HP, a disease provoked by an immunopathologic reaction to inhaled antigens, are two common interstitial lung diseases with uncertain pathogenic mechanisms. Previously, we have shown in other upper and lower airway diseases that immunoglobulin free light chains (FLCs are increased and may be involved in initiating a local inflammation. In this study we explored if such a mechanism may also apply to HP and IPF. METHODS: In this study we examined the presence of FLC in serum and BAL fluid from 21 IPF and 22 HP patients and controls. IgG, IgE and tryptase concentrations were measured in BAL fluid only. The presence of FLCs, plasma cells, B cells and mast cells in lung tissue of 3 HP and 3 IPF patients and 1 control was analyzed using immunohistochemistry. RESULTS: FLC concentrations in serum and BAL fluid were increased in IPF and HP patients as compared to control subjects. IgG concentrations were only increased in HP patients, whereas IgE concentrations were comparable to controls in both patient groups. FLC-positive cells, B cells, plasma cells, and large numbers of activated mast cells were all detected in the lungs of HP and IPF patients, not in control lung. CONCLUSION: These results show that FLC concentrations are increased in serum and BAL fluid of IPF and HP patients and that FLCs are present within affected lung tissue. This suggests that FLCs may be involved in mediating pathology in both diseases.

  19. Temporal Progression of Pneumonic Plague in Blood of Nonhuman Primate: A Transcriptomic Analysis.

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    Rasha Hammamieh

    Full Text Available Early identification of impending illness during widespread exposure to a pathogenic agent offers a potential means to initiate treatment during a timeframe when it would be most likely to be effective and has the potential to identify novel therapeutic strategies. The latter could be critical, especially as antibiotic resistance is becoming widespread. In order to examine pre-symptomatic illness, African green monkeys were challenged intranasally with aerosolized Yersinia pestis strain CO92 and blood samples were collected in short intervals from 45 m till 42 h post-exposure. Presenting one of the first genomic investigations of a NHP model challenged by pneumonic plague, whole genome analysis was annotated in silico and validated by qPCR assay. Transcriptomic profiles of blood showed early perturbation with the number of differentially expressed genes increasing until 24 h. By then, Y. pestis had paralyzed the host defense, as suggested by the functional analyses. Early activation of the apoptotic networks possibly facilitated the pathogen to overwhelm the defense mechanisms, despite the activation of the pro-inflammatory mechanism, toll-like receptors and microtubules at the port-of-entry. The overexpressed transcripts encoding an early pro-inflammatory response particularly manifested in active lymphocytes and ubiquitin networks were a potential deviation from the rodent models, which needs further verification. In summary, the present study recognized a pattern of Y. pestis pathogenesis potentially more applicable to the human system. Independent validation using the complementary omics approach with comprehensive evaluation of the organs, such as lungs which showed early bacterial infection, is essential.

  20. Thin-Section CT Characteristics and Longitudinal CT Follow-up of Chemotherapy Induced Interstitial Pneumonitis: A Retrospective Cohort Study.

    Science.gov (United States)

    Lee, Han Na; Kim, Mi Young; Koo, Hyun Jung; Kim, Sung-Soo; Yoon, Dok Hyun; Lee, Jae Cheol; Song, Jin Woo

    2016-01-01

    To describe the computed tomography (CT) features of chemotherapy-induced interstitial pneumonitis (CIIP) with longitudinal follow-up.The study was approved by the local ethics committee. One hundred consecutive patients with CIIP between May 2005 and March 2015 were retrospectively enrolled. The initial CT was reviewed by 2 independent chest radiologists and categorized into 1 of 4 CT patterns in accordance with the 2013 guidelines for idiopathic interstitial pneumonia: nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), hypersensitivity pneumonitis (HP) mimicking desquamative interstitial pneumonitis, and diffuse alveolar damage (DAD). We assessed semiquantitative analysis on a 5% scale to assess the extent of parenchymal abnormalities (emphysema, reticulation, ground-glass opacity, consolidation, honeycombing cyst) and their distribution on initial (n = 100), subsequent (n = 87), and second follow-up CT (n = 48). Interval changes in extent on follow-up CT were compared using paired t test. The clinic-radiologic factors were compared between Group 1 (NSIP and OP patterns) and Group 2 (HP and DAD patterns) using χ and independent t tests.The most common pattern of CIIP on the initial CT was HP (51%), followed by NSIP (23%), OP (20%), and DAD (6%). Diffuse ground-glass opacity was the most common pulmonary abnormality. The predominant distribution was bilateral (99%) and symmetric (82%), with no craniocaudal (60%) or axial (79%) dominance. Subsequent and second follow-up CTs showed decreased extent of total pulmonary abnormalities (P CIIP, Group 2 CIIP was more likely to be caused by molecularly targeted drugs (P = 0.030), appeared earlier (P = 0.034), and underwent more complete resolution (P CIIP is appropriate and practical in interpreting radiological findings.

  1. Radiation nephritis causing nephrotic syndrome

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    Jennette, J.C.; Ordonez, N.G.

    1983-12-01

    Clinical symptoms of acute radiation nephritis with nephrotic syndrome developed in a fifty-six-year-old woman after abdominal radiation therapy for an astrocytoma of the spinal cord. The diagnosis of radiation nephritis was confirmed by renal biopsy. To our knowledge, this is the first documented case of radiation nephritis associated with nephrotic syndrome.

  2. Absence of toxicity with hypofractionated 3-dimensional radiation therapy for inoperable, early stage non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Vuong Te

    2006-11-01

    Full Text Available Abstract Purpose Hypofractionated radiotherapy may overcome repopulation in rapidly proliferating tumors such as lung cancer. It is more convenient for the patients and reduces health care costs. This study reports our results on patients with medically inoperable, early stage, non-small cell lung cancer (NSCLC treated with hypofractionation. Materials and methods Stage T1-2N0 NSCLC patients were treated with hypofractionation alone, 52.5 Gy/15 fractions, in 3 weeks, with 3-dimensional conformal planning. T1-2N1 patients with the hilar lymphnode close to the primary tumor were also eligible for this treatment. We did not use any approach to reduce respiratory motion, but it was monitored in all patients. Elective nodal radiotherapy was not performed. Routine follow up included assessment for acute and late toxicity and radiological tumor response. Median follow up time was 29 months for the surviving patients. Results Thirty-two patients with a median age of 76 years, T1 = 15 and T2 = 17, were treated. Median planning target volume (PTV volume was 150cc and median V16 of both lungs was 13%. The most important finding of this study is that toxicity was minimal. Two patients had grade ≤ 2 acute pneumonitis and 3 had mild (grade 1 acute esophagitis. There was no late toxicity. Actuarial 1 and 2-year overall survival rates are 78% and 56%, cancer specific survival rates (CSS are 90% and 74%, and local relapse free survival rates are 93% and 76% respectively. Conclusion 3-D planning, involved field hypofractionation at a dose of 52.5 Gy in 15 daily fractions is safe, well tolerated and easy radiation treatment for medically inoperable lung cancer patients. It shortens by half the traditional treatment. Results compare favorably with previously published studies. Further studies are needed to compare similar technique with other treatments such as surgery and stereotactic radiotherapy.

  3. Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy

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    Bazan, Jose G.; Luxton, Gary; Kozak, Margaret M.; Anderson, Eric M.; Hancock, Steven L.; Kapp, Daniel S.; Kidd, Elizabeth A.; Koong, Albert C.; Chang, Daniel T., E-mail: dtchang@stanford.edu

    2013-12-01

    Purpose: To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. Methods and Materials: We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (