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Sample records for acute chemical pneumonitis

  1. [Acute and subacute chemical pneumonitis].

    PubMed

    Andujar, P; Nemery, B

    2009-10-01

    Acute or subacute chemical-induced lung injury is rarely compound specific and is most often caused by an accidental occupational, domestic or environmental exposure to an inhaled chemical agent. The industrial disaster that happened in Bhopal in 1984, accidental poisoning with chlorine and petroleum hydrocarbons and also vesicant gases used during conflicts, are specific examples. Rarely, a chemical agent can cause lung damage by being ingested and reaching the lung through the systemic circulation (for example accidental or deliberate paraquat ingestion). Household accidents should not be underestimated. An important cause of household accidents is chlorine inhalation resulting from mixing bleach with acids such as the scale removers used to clean toilets. Chemical agents can provoke direct and/or indirect damage to the respiratory tract. The acute or subacute clinical manifestations resulting from inhalation of chemical agents are very varied and include inhalation fevers, acute non-cardiogenic pulmonary oedema, adult respiratory distress syndrome, reactive airways dysfunction syndrome and acute or subacute pneumonitis. The site and the severity of chemical-induced respiratory damage caused by inhaled chemical agents depend mainly on the nature and the amount of the agent inhaled. The immediate and long-term prognosis and possible sequelae are also variable. This review excludes infectious or immunologically induced acute respiratory diseases. PMID:19953031

  2. Chemical pneumonitis

    MedlinePlus

    ... Do not siphon gas or kerosene. Images Lungs Respiratory system References Blanc PD. Acute pulmonary responses to toxic exposures. In: Mason RJ, Broaddus CV, Martin TR, et al, eds. Murray & Nadel's Textbook of Respiratory Medicine . 5th ed. Philadelphia, PA: Saunders Elsevier; 2010: ...

  3. Phenytoin-induced acute hypersensitivity pneumonitis.

    PubMed

    Periwal, Pallavi; Joshi, Sharad; Gothi, Rajesh; Talwar, Deepak

    2015-01-01

    Lungs are target organs for toxic effects of various drugs due to many reasons. Diphenylhydantoin (DPH) is reported to have many extrapulmonary side effects. We are presenting a case of acute hypersensitivity pneumonitis (HP) secondary to DPH, presenting with respiratory failure. Acute HP with respiratory failure is an uncommon drug side effect of the DPH therapy and is a diagnosis of exclusion. It requires detailed workup and exclusion of other causes along with evidence of improvement in the patient's condition after withholding DPH. PMID:26664176

  4. Phenytoin-induced acute hypersensitivity pneumonitis

    PubMed Central

    Periwal, Pallavi; Joshi, Sharad; Gothi, Rajesh; Talwar, Deepak

    2015-01-01

    Lungs are target organs for toxic effects of various drugs due to many reasons. Diphenylhydantoin (DPH) is reported to have many extrapulmonary side effects. We are presenting a case of acute hypersensitivity pneumonitis (HP) secondary to DPH, presenting with respiratory failure. Acute HP with respiratory failure is an uncommon drug side effect of the DPH therapy and is a diagnosis of exclusion. It requires detailed workup and exclusion of other causes along with evidence of improvement in the patient's condition after withholding DPH. PMID:26664176

  5. Severe acute measles pneumonitis: virus isolation in bronchoalveolar lavage fluid.

    PubMed

    Suter, Cosima; Buergi, Urs; Eigenmann, Katja; Franzen, Daniel

    2015-01-01

    In the past few years, several endemic outbreaks of measles have been recognised, not only in children but also in adults, with severe and, occasionally, even fatal complications, possibly due to delayed diagnosis of the disease in adult medicine and decreasing vaccination rates. Furthermore, the treatment consists of supportive measures only. We present a case of severe measles pneumonitis in a 42-year-old man, a travel returnee, proven by direct virus isolation with PCR from bronchoalveolar lavage fluid. CT findings and pulmonary function testing revealed features of obstructive bronchiolitis; the patient was successfully treated with corticosteroids. He fully recovered, and lung function measurement returned to normal values. We conclude that acute measles can present as obstructive bronchiolitis and may be successfully treated with corticosteroids. PMID:26508116

  6. Life-threatening acute pneumonitis in mixed connective tissue disease: a case report and literature review.

    PubMed

    Rath, Eva; Zandieh, Shahin; Löckinger, Alexander; Hirschl, Mirko; Klaushofer, Klaus; Zwerina, Jochen

    2015-10-01

    Mixed connective tissue disease (MCTD) is a rare connective tissue disease frequently involving the lungs. The main characteristic is a systemic sclerosis-like picture of slowly progressing interstitial lung disease consistent with lung fibrosis, while pulmonary arterial hypertension is rare. Herein, we present a case of a newly diagnosed MCTD patient developing life-threatening acute pneumonitis similar to lupus pneumonitis. Previous literature on this exceptionally rare complication of MCTD is reviewed and differential diagnosis and management discussed. PMID:26142172

  7. Hypersensitivity pneumonitis

    MedlinePlus

    Hypersensitivity pneumonitis usually occurs in people who work in places where there are high levels of organic dusts, fungus, or molds. Long-term exposure can lead to lung inflammation and acute lung disease . ...

  8. Systemic lupus erythematosus presenting as acute lupus pneumonitis in a young female

    PubMed Central

    Chattopadhyay, B; Chatterjee, A; Maiti, A; Debnath, NB

    2015-01-01

    Acute lupus pneumonitis is a rare initial presentation of systemic lupus erythematosus (SLE). We report a 19-year-old female presenting with fever and recurrent hemoptysis with radiological evidence of parenchymal lung involvement with mild pleural effusion. Subsequent development of malar and discoid rash with anti-nuclear antibodies (ANA) and anti-dsDNA positivity clinched the diagnosis. Her clinical signs and symptoms resolved with a course of intravenous pulse methyl-prednisolone along with radiological resolution. PMID:25766350

  9. The diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis

    PubMed Central

    Elmoslemany, Ahmed M.

    2016-01-01

    The goal of this study was to assess the diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis. Blood samples were collected from 56 sheep (36 naturally infected with Pasteurella multocida and 20 healthy controls) belonging to one farm in Eastern region, Saudi Arabia. Serum samples were evaluated for acute phase proteins (Haptoglobin (Hp), serum amyloid A (SAA) and fibrinogen (Fb)), and the proinflammatory cytokines (interleukins (IL-1α, IL-1β, and IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-ϒ)). Additionally, nasopharyngeal swabs and bronchoalveolar lavages were collected from all animals for bacteriological examinations. Receiver operating characteristic curve was used to assess the diagnostic performance of each parameter. All parameters showed moderate to high degree of positive correlation with case-control status. There was no significant difference in the area under the curve (AUC) among acute phase proteins; however, both Hp and SAA showed better sensitivity and specificity than Fb. The proinflammatory cytokines (IL1-α, IL1-β, and IL6) showed similar and highly accurate diagnostic performance (AUC > 0.9), whereas IFN-ϒ was moderately accurate (AUC = 0.79). In conclusion, this study confirms the value of acute phase proteins and cytokines as diagnostic biomarkers of naturally occuring pneumonic pasteurellosis in sheep. PMID:27547520

  10. The diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis.

    PubMed

    El-Deeb, Wael M; Elmoslemany, Ahmed M

    2016-01-01

    The goal of this study was to assess the diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis. Blood samples were collected from 56 sheep (36 naturally infected with Pasteurella multocida and 20 healthy controls) belonging to one farm in Eastern region, Saudi Arabia. Serum samples were evaluated for acute phase proteins (Haptoglobin (Hp), serum amyloid A (SAA) and fibrinogen (Fb)), and the proinflammatory cytokines (interleukins (IL-1α, IL-1β, and IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-ϒ)). Additionally, nasopharyngeal swabs and bronchoalveolar lavages were collected from all animals for bacteriological examinations. Receiver operating characteristic curve was used to assess the diagnostic performance of each parameter. All parameters showed moderate to high degree of positive correlation with case-control status. There was no significant difference in the area under the curve (AUC) among acute phase proteins; however, both Hp and SAA showed better sensitivity and specificity than Fb. The proinflammatory cytokines (IL1-α, IL1-β, and IL6) showed similar and highly accurate diagnostic performance (AUC > 0.9), whereas IFN-ϒ was moderately accurate (AUC = 0.79). In conclusion, this study confirms the value of acute phase proteins and cytokines as diagnostic biomarkers of naturally occuring pneumonic pasteurellosis in sheep. PMID:27547520

  11. Impact of Preexisting Interstitial Lung Disease on Acute, Extensive Radiation Pneumonitis: Retrospective Analysis of Patients with Lung Cancer

    PubMed Central

    Ozawa, Yuichi; Abe, Takefumi; Omae, Minako; Matsui, Takashi; Kato, Masato; Hasegawa, Hirotsugu; Enomoto, Yasunori; Ishihara, Takeaki; Inui, Naoki; Yamada, Kazunari; Yokomura, Koshi; Suda, Takafumi

    2015-01-01

    Introduction This study investigated the clinical characteristics and predictive factors for developing acute extended radiation pneumonitis with a focus on the presence and radiological characteristics of preexisting interstitial lung disease. Methods Of 1429 irradiations for lung cancer from May 2006 to August 2013, we reviewed 651 irradiations involving the lung field. The presence, compatibility with usual interstitial pneumonia, and occupying area of preexisting interstitial lung disease were retrospectively evaluated by pretreatment computed tomography. Cases of non-infectious, non-cardiogenic, acute respiratory failure with an extended bilateral shadow developing within 30 days after the last irradiation were defined as acute extended radiation pneumonitis. Results Nine (1.4%) patients developed acute extended radiation pneumonitis a mean of 6.7 days after the last irradiation. Although preexisting interstitial lung disease was found in 13% of patients (84 patients), 78% of patients (7 patients) with acute extended radiation pneumonitis cases had preexisting interstitial lung disease, which resulted in incidences of acute extended radiation pneumonitis of 0.35 and 8.3% in patients without and with preexisting interstitial lung disease, respectively. Multivariate logistic analysis indicated that the presence of preexisting interstitial lung disease (odds ratio = 22.6; 95% confidence interval = 5.29–155; p < 0.001) and performance status (≥2; odds ratio = 4.22; 95% confidence interval = 1.06–20.8; p = 0.049) were significant predictive factors. Further analysis of the 84 patients with preexisting interstitial lung disease revealed that involvement of more than 10% of the lung field was the only independent predictive factor associated with the risk of acute extended radiation pneumonitis (odds ratio = 6.14; 95% confidence interval = 1.0–37.4); p = 0.038). Conclusions Pretreatment computed tomography evaluations of the presence of and area size occupied

  12. Hypersensitivity Pneumonitis.

    PubMed

    Wysong, Kristi; Phillips, Jennan A; Hammond, Stephanie

    2016-06-01

    Chronic exposure to a broad array of antigens after workers inhale aerosolized organic dust particles from mold, animal dander, bird droppings, and chemicals, especially pesticides or herbicides, increases risk for hypersensitivity pneumonitis. Several demographic characteristics of immigrant workers in farming, poultry processing, construction, and landscaping increase this worker population's risk. PMID:27067273

  13. Chemical pneumonitis

    MedlinePlus

    ... of the most common dangerous, inhaled substances include: Chlorine gas (which are breathed in from cleaning materials such as chlorine bleach, during industrial accidents, or near swimming pools) ...

  14. Acute lupus pneumonitis followed by intestinal pseudo-obstruction in systemic lupus erythematosus: A case report

    PubMed Central

    JI, CAIHONG; YU, XING; WANG, YONG; SHI, LUFENG

    2016-01-01

    Intestinal pseudo-obstruction (IpsO) and acute lupus pneumonitis (ALP) are uncommon severe complications of systemic lupus erythematosus (SLE). The present study reports the case of a 26-year-old female who presented with abdominal pain, nausea and vomiting as initial symptoms. Computed tomography (CT) scanning revealed the jejunal wall was thickened and streaky, mimicking the presentation of intestinal obstruction. Following emergency surgery, the patient's general condition was aggravated, with evident limb erythematous rashes. A series of laboratory examinations revealed SLE, and combined with patient's medical history IpsO was diagnosed, with a disease Activity Index score of 10. During the therapeutic period, high fever, dyspnea and oxygen saturation (SaO2) reductions were detected, and CT scans indicated lung infiltration, excluding other causes through a comprehensive infectious work-up and a bronchoalveolar lavage examination. ALP was confirmed and treated with high-dose methylprednisolone and gamma globulin supplement. The patient responded well and was discharged in 2 weeks. In the one-year tapering period and after stopping corticosteroids, the patient recovered well with no relapse detected. In conclusion, the manifestation of IpsO in SLE is rare and represents a challenge for the surgeon to establish the correct diagnosis and avoid inappropriate surgical intervention. ALP may be the consequence of emergency surgery, and immediate high-dose glucocorticoid therapy is recommended. PMID:27347044

  15. Predictive factors for acute radiation pneumonitis in postoperative intensity modulated radiation therapy and volumetric modulated arc therapy of esophageal cancer

    PubMed Central

    Zhao, Yaqin; Chen, Lu; Zhang, Shu; Wu, Qiang; Jiang, Xiaoqin; Zhu, Hong; Wang, Jin; Li, Zhiping; Xu, Yong; Zhang, Ying Jie; Bai, Sen; Xu, Feng

    2015-01-01

    Background Radiation pneumonitis (RP) is a common side reaction in radiotherapy for esophageal cancer. There are few reports about RP in esophageal cancer patients receiving postoperative intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). This study aims to analyze clinical or dosimetric factors associated with RP, and provides data for radiotherapy planning. Methods We reviewed 68 postoperative esophageal cancer patients who were treated with radiotherapy at the West China Hospital from October 2010 to November 2012 to identify any correlation between the clinical or dosimetric parameters and acute radiation pneumonitis (ARP) or severe acute radiation pneumonitis (SARP) by t-test, chi-square test, and logistic regression analysis. Results Of the 68 patients, 33 patients (48.5%) developed ARP, 13 of which (19.1%) developed SARP. Of these 33 patients, 8 (11.8%), 12 (17.6%), 11 (16.2%), and 2 (2.9%) patients were grade 1, 2, 3, and 4 ARP, respectively. Univariate analysis showed that lung infection during radiotherapy, use of VMAT, mean lung dose (MLD), and dosimetric parameters (e.g. V20, V30) are significantly correlated with RP. Multivariate analysis found that lung infection during radiotherapy, MLD ≥ 12 Gy, and V30 ≥ 13% are significantly correlated with an increased risk of RP. Conclusion Lung infection during radiotherapy and low radiation dose volume distribution were predictive factors associated with RP and should be accounted for during radiation planning. PMID:26273335

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

    PubMed Central

    Barrios, M. N.; Martín, T.; Sánchez, M. L.; Buitrago, J. M. González; Jiménez, A.

    1995-01-01

    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. PMID:18475615

  17. Hypersensitivity Pneumonitis

    MedlinePlus

    ... Hypersensitivity Pneumonitis Also known as extrinsic allergic alveolitis, bird fancier’s lung, farmer’s lung, hot tub lung, and ... May 27, 2016 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA OIG CONTACT US National ...

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

    PubMed Central

    Chung, Min Jae; Lee, Jae Hee

    2015-01-01

    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. PMID:26770905

  19. Pulmonary complications of chemical pneumonía: a case report.

    PubMed

    Bahceci Erdem, Semiha; Nacaroglu, Hikmet T; Isgüder, Rana; Unsal Karkiner, Canan S; Alper, Hüdaver; Can, Demet

    2016-08-01

    Hydrocarbon aspiration (HA) can cause significant lung disease by inducing an inflammatory response, hemorrhagic exudative alveolitis, and loss of surfactant function. The most serious side effect of HA is aspiration pneumonia. Pneumothorax, pneumatocele, acute respiratory distress syndrome (ARDS), pulmonary abscess, bronchopleural fistula, bilateral hemorrhagic pleural effusion and pyopneumothorax were previously reported. Hereby we report a patient hospitalized due to aspiration pneumonia who developed pleurisy and pneumothorax after drinking paint thinner. It is presented as it was seldom reported in children to cause distinct pulmonary complications. Patients with complaints associated withhydrocarbon poisoning must be fully evaluated. They must not be discharged from the hospital early and must be followed for at least 48 hours even if they don't have respiratory symptoms. It should be kept in mind that severe pulmonary complications can develop in patients with chemical pneumonia. PMID:27399025

  20. Excessive Neutrophils and Neutrophil Extracellular Traps Contribute to Acute Lung Injury of Influenza Pneumonitis

    PubMed Central

    Narasaraju, Teluguakula; Yang, Edwin; Samy, Ramar Perumal; Ng, Huey Hian; Poh, Wee Peng; Liew, Audrey-Ann; Phoon, Meng Chee; van Rooijen, Nico; Chow, Vincent T.

    2011-01-01

    Complications of acute respiratory distress syndrome (ARDS) are common among critically ill patients infected with highly pathogenic influenza viruses. Macrophages and neutrophils constitute the majority of cells recruited into infected lungs, and are associated with immunopathology in influenza pneumonia. We examined pathological manifestations in models of macrophage- or neutrophil-depleted mice challenged with sublethal doses of influenza A virus H1N1 strain PR8. Infected mice depleted of macrophages displayed excessive neutrophilic infiltration, alveolar damage, and increased viral load, later progressing into ARDS-like pathological signs with diffuse alveolar damage, pulmonary edema, hemorrhage, and hypoxemia. In contrast, neutrophil-depleted animals showed mild pathology in lungs. The brochoalveolar lavage fluid of infected macrophage-depleted mice exhibited elevated protein content, T1-α, thrombomodulin, matrix metalloproteinase-9, and myeloperoxidase activities indicating augmented alveolar-capillary damage, compared to neutrophil-depleted animals. We provide evidence for the formation of neutrophil extracellular traps (NETs), entangled with alveoli in areas of tissue injury, suggesting their potential link with lung damage. When co-incubated with infected alveolar epithelial cells in vitro, neutrophils from infected lungs strongly induced NETs generation, and augmented endothelial damage. NETs induction was abrogated by anti-myeloperoxidase antibody and an inhibitor of superoxide dismutase, thus implying that NETs generation is induced by redox enzymes in influenza pneumonia. These findings support the pathogenic effects of excessive neutrophils in acute lung injury of influenza pneumonia by instigating alveolar-capillary damage. PMID:21703402

  1. 017. Exogenous acute lipoid pneumonitis from animal fat aspiration (part of intestine)

    PubMed Central

    Gkika, Dimitra; Manos, Emmanouil; Kolovos, Dimitrios; Batsouli, Vassiliki; Pathiaki, Eirini; Mavromati, Evagelia; Divani, Smaroula; Vardouli, Anna; Panagopoulos, Angelos; Karkanis, Konstantinos; Angel, Jacob

    2015-01-01

    Objective In the aspiration of animal fats, bronchoscopy is promptly necessary, not only for removing the foreign body but also for its therapeutic importance in order to avoid severe lipoid pneumonia, because fat acids are very toxic for the bronchial mucosa. Methods Patient 84 years old, nonsmoker, with a medical history of heart disease under acenocoumarol, referred accidental aspiration of cooked animal intestine, 12 hours ago, with rough cough and dyspnea that started instantly. To be noted, the patient presented with wheezing in both lungs. Thoracic CT scan images reveal a suspicion of aspiration, confirmed by indirectly evidence (right middle lobe atelectasis and also mediastinum transposition to the left and consolidation with atelectasis in the left lower lobe, as evidence of previous infections-possible aspirations, emerged from his case story). Therefore, urgent bronchoscopy was performed and the foreign body, that was movable with the cough, was removed. Bronchial lavage was performed due to acute infection in whole bronchial tree. A reactive granuloma tissue was noted in the entrance of the middle lobe, but because of the anticoagulant intake biopsy wasn’t performed. During his hospitalization the patient was under antibiotics, bronchodilators and corticosteroids. Results At the time of revaluation, two weeks after, the patient was non symptomatic while the new CT scan showed evidence of residual infection in the left lung and atelectasis of the right middle lobe on the left. Bronchoscopy was reperformed and biopsy was taken in the entrance of the right middle lobe because of the noted reactive granuloma tissue, seen at the first bronchoscopy. No signs of bronchial inflammation were found (impressive improvement due to immediate intervention). Conclusions Animal fat aspiration causes acute bronchial inflammation and therefore, lipoid pneumonia within a few hours, due to rapid hydrolysis of releasing fatty acids. Removing the animal fat with the

  2. Fatal measles pneumonitis during Hodgkin's lymphoma.

    PubMed

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

    2013-01-01

    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. PMID:24105383

  3. Fatal measles pneumonitis during Hodgkin's lymphoma

    PubMed Central

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

    2013-01-01

    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. PMID:24105383

  4. Successful treatment of gefitinib-induced acute interstitial pneumonitis with corticosteroid and non-invasive BIPAP-ventilation.

    PubMed

    Zhang, Yalei; Yang, Haihong; Zhao, Meiling; He, Jianxing

    2012-06-01

    This is the case of a 63 year-old male who was diagnosed adenocarcinoma in the left upper lung with ipsilateral malignant pleural effusion. At diagnosis it had already spread to left pulmonary HLN (hilar lymph node) and left supraclavicular lymph node and mediastinal lymph nodes. The patient received combined chemotherapy with bevacizumab and GP (gemcitabine and carboplatin) for 6 courses. Disease progression on chest CT scan was recognized, daily treatment with oral gefitinib (250 mg/day) was commenced. One week later, he was admitted under the impression of gefitinib-related interstitial pneumonitis, gefitinib was discontinued immediately and methylprednisolone with BIPAP assisted ventilation were used. The patient was followed up for 2 months after the start of treatment with corticosteroids and BIPAP assisted ventilation and remained well. PMID:22754672

  5. Successful treatment of gefitinib-induced acute interstitial pneumonitis with corticosteroid and non-invasive BIPAP-ventilation

    PubMed Central

    Zhang, Yalei; Yang, Haihong; Zhao, Meiling

    2012-01-01

    This is the case of a 63 year-old male who was diagnosed adenocarcinoma in the left upper lung with ipsilateral malignant pleural effusion. At diagnosis it had already spread to left pulmonary HLN (hilar lymph node) and left supraclavicular lymph node and mediastinal lymph nodes. The patient received combined chemotherapy with bevacizumab and GP (gemcitabine and carboplatin) for 6 courses. Disease progression on chest CT scan was recognized, daily treatment with oral gefitinib (250 mg/day) was commenced. One week later, he was admitted under the impression of gefitinib-related interstitial pneumonitis, gefitinib was discontinued immediately and methylprednisolone with BIPAP assisted ventilation were used. The patient was followed up for 2 months after the start of treatment with corticosteroids and BIPAP assisted ventilation and remained well. PMID:22754672

  6. Hydrocodone snorting leading to hypersensitivity pneumonitis

    PubMed Central

    Vijayaraghavan, Vimala

    2016-01-01

    We present a case of hypersensitivity pneumonitis caused by intranasal abuse of the prescription narcotic hydrocodone. The patient's clinical course was complicated by acute respiratory failure. A chest radiograph showed diffuse bilateral opacities. The patient was treated with noninvasive ventilation, a high dose of intravenous steroids, and bronchodilators, resulting in improvement of symptoms and radiographic appearance. PMID:27365873

  7. Treatment-Related Pneumonitis and Acute Esophagitis in Non-Small-Cell Lung Cancer Patients Treated With Chemotherapy and Helical Tomotherapy

    SciTech Connect

    Song, Chang Hoon; Pyo, Hongryull; Moon, Sung Ho; Kim, Tae Hyun; Kim, Dae Woong; Cho, Kwan Ho

    2010-11-01

    Purpose: To assess clinical outcomes and complications in patients with non-small-cell lung cancer (NSCLC) treated with helical tomotherapy (HT) with or without chemotherapy. Methods and Materials: Data from 37 NSCLC patients treated between January 2007 and August 2008 were analyzed retrospectively. Twenty-eight patients had Stage III disease. Concurrent and neoadjuvant chemotherapy was given to 24 and 14 patients, respectively. Radiotherapy was delivered to a total dose of 60-70.4 Gy at 2.0-2.4 Gy per fraction to the gross tumor volume and 50-64 Gy at 1.8-2.0 Gy per fraction to the planning target volume. Results: With a median follow-up of 18 months (range, 6-27 months), 2-year local control and overall survival rates were 63% and 56% for all 37 patients, respectively, and were 78% and 75% for the patients with Stage III disease who received concurrent chemoradiotherapy alone. Acute esophagitis and treatment-related pneumonitis (TRP) {>=}Grade 3 occurred in 5 and 7 patients, respectively. Four patients died of treatment-related death (TRD) after HT. In univariate analysis, poor performance status, total lung V{sub 5}, contralateral lung (CL) V{sub 5}, and V{sub 10} were associated with TRD. Only CL V{sub 5} remained significant in the multivariate analysis (p = 0.029). Conclusions: HT with chemotherapy has shown promising clinical outcomes, esophagitis, and TRPs. However, HT has produced a somewhat high rate of fatal pulmonary complications. Our data suggest that CL V{sub 5} should be considered and kept as low as possible (<60%) in addition to the conventional dosimetric factors.

  8. An atypical case of fulminant interstitial pneumonitis induced by carbamazepine.

    PubMed

    Narita, Hideyuki; Ozawa, Takuro; Nishiyama, Takahisa; Matsumoto, Shohei; Watanabe, Seigo; Isshiki, Atsushi

    2009-01-01

    Carbamazepine is a therapeutic anticonvulsant, used to manage pain. We often use it to treat trigeminal and post-herpes zoster neuralgias. Interstitial pneumonitis (IP) is a known adverse consequence of using carbamazepine, with bronchiolitis obliterans and organizing pneumonitis. (BOOP) drug-induced IP as typical examples. Here we described a patient with post-herpes zoster neuralgia, who suffered from drug-induced acute IP that differed from cases typically induced by carbamazepine. PMID:19149523

  9. Perindopril-associated pneumonitis.

    PubMed

    Benard, A; Melloni, B; Gosselin, B; Bonnaud, F; Wallaert, B

    1996-06-01

    We report two cases of perindopril-associated pneumonitis with typical drug-induced clinical features. In the first case, biopsies showed granulomatous sarcoid-like lesions; in the second, bronchial wall eosinophil infiltratf2p4was reported with increased blood eosinophil count. In these two cases, improvement was obtained by withdrawal of the drug and was completed with steroids. All other causes were ruled out. Angiotensin-converting enzyme inhibitor (ACEI)-induced pneumonitis is still rare but has to be recognized as a real side-effect. PMID:8804953

  10. Management of hypersensivity pneumonitis

    PubMed Central

    2013-01-01

    Hypersensitivity pneumonitis (HP) is an interstitial lung disease due to a combined type III and IV reaction with a granulomatous inflammation, caused by cytotoxic delayed hypersensitivity lymphocytes, in a Th1/Th17 milieu, chaperoned by a deficient suppressor function of T regulatory cells. Skewing toward a Th2 phenotype is reported for chronic HP. Phenotypic expression and severity depends on environmental and/or host genetic and immune co-factors. The wide spectrum of causative antigens is continuously up-dated with new sources of airborne organic particles and drug-induced HP. The diagnosis requires a detailed history, measurement of environmental exposure, pulmonary function tests, imaging, detection of serum specific antibodies, broncho-alveolar lavage, antigen-induced lymphocyte proliferation, environmental or laboratory-controlled inhalation challenge and lung biopsy. Complete antigen avoidance is the best therapeutic measure, although very difficult to achieve in some cases. Systemic steroids are of value for subacute and chronic forms of HP, but do not influence long term outcome. Manipulation of the immune response in HP holds future promise. PMID:23374544

  11. Influenza SIRS with Minimal Pneumonitis

    PubMed Central

    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.

  12. Occupational hypersensitivity pneumonitis: an EAACI position paper.

    PubMed

    Quirce, S; Vandenplas, O; Campo, P; Cruz, M J; de Blay, F; Koschel, D; Moscato, G; Pala, G; Raulf, M; Sastre, J; Siracusa, A; Tarlo, S M; Walusiak-Skorupa, J; Cormier, Y

    2016-06-01

    The aim of this document was to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the diagnosis and management of this condition. Occupational hypersensitivity pneumonitis (OHP) is an immunologic lung disease resulting from lymphocytic and frequently granulomatous inflammation of the peripheral airways, alveoli, and surrounding interstitial tissue which develops as the result of a non-IgE-mediated allergic reaction to a variety of organic materials or low molecular weight agents that are present in the workplace. The offending agents can be classified into six broad categories that include bacteria, fungi, animal proteins, plant proteins, low molecular weight chemicals, and metals. The diagnosis of OHP requires a multidisciplinary approach and relies on a combination of diagnostic tests to ascertain the work relatedness of the disease. Both the clinical and the occupational history are keys to the diagnosis and often will lead to the initial suspicion. Diagnostic criteria adapted to OHP are proposed. The cornerstone of treatment is early removal from exposure to the eliciting antigen, although the disease may show an adverse outcome even after avoidance of exposure to the causal agent. PMID:26913451

  13. Acute oral toxicities of wildland fire control chemicals to birds

    USGS Publications Warehouse

    Vyas, N.B.; Spann, J.W.; Hill, E.F.

    2009-01-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24 h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R?) and two Class A fire suppressant foams (Silv-Ex? and Phos-Chek WD881?) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881? and Silv-Ex? were above the predetermined 2000 mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R? because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

  14. Acute oral toxicities of wildland fire control chemicals to birds.

    PubMed

    Vyas, Nimish B; Spann, James W; Hill, Elwood F

    2009-03-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R) and two Class A fire suppressant foams (Silv-Ex and Phos-Chek WD881) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881 and Silv-Ex were above the predetermined 2000mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested. PMID:19038451

  15. Paediatric feather duvet hypersensitivity pneumonitis.

    PubMed

    Jordan, Louise E; Guy, Emma

    2015-01-01

    A previously well 12-year-old boy was admitted with a second insidious episode of dyspnoea, dry cough, anorexia, weight loss and chest pain. At admission, he had an oxygen requirement, significantly impaired lung function and reduced exercise tolerance. Initial forced expiratory volume in 1 s was 26%; a 3 min exercise test stopped at 1 min 50 when saturations dropped to 85%. CT scan showed ground-glass nodularity with lymphadenopathy. Bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia and viruses were negative, and microbiology results for the BAL were reported in the absence of histology. This is because at the time the BAL samples were collected, a lung biopsy was performed. The biopsy was consistent with hypersensitivity pneumonitis. Echo was normal and CT pulmonary angiography negative. After taking a thorough history, exposure to feather duvets prior to each episode was elicited. IgG of avian precipitants was raised at 10.6 mgA/L (normal <10 mgA/L). Clinical improvement began with avoidance of exposure, while the boy was an inpatient. Antigen avoidance continued on discharge. He continues to improve since discharge. The condition was diagnosed as hypersensitivity pneumonitis secondary to exposure to antigens from feather duvets. PMID:26113584

  16. Identifying and designing chemicals with minimal acute aquatic toxicity

    PubMed Central

    Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T.; Zimmerman, Julie Beth

    2015-01-01

    Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure–activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical–chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard. PMID:24639521

  17. Radiation pneumonitis following large single dose irradiation: a re-evaluation based on absolute dose to lung

    SciTech Connect

    Van Dyk, J.; Keane, T.J.; Kan, S.; Rider, W.D.; Fryer, C.J.H.

    1981-04-01

    The acute radiation pneumonitis syndrome is a major complication for patients receiving total thoracic irradiation in a large single dose. Previous studies have evaluated the onset of radiation pneumonitis on the basis of radiation doses calculated assuming unit density tissues. In this report, the incidence of radiation pneumonitis is determined as a function of absolute dose to lung. A simple algorithm relating dose correction factor to anterior-posterior patient diameter has been derived using a CT-aided treatment planning system. This algorithm was used to determine, retrospectively, the dose to lung for a group of 303 patients who had been treated with large field irradiation techniques. Of this group, 150 patients had no previous lung disease and had virtually no additional lung irradiation prior or subsequent to their large field treatment. The actuarial incidence of radiation pneumonitis versus dose to lung was evaluated using a simplified probit analysis. The resultant best fit sigmoidal complication curve demonstrates the onset of radiation pneumonitis to occur at about 750 rad with the 5% actuarial incidence occurring at approximately 820 rad. The errors associated with the dose determination procedure as well as the actuarial incidence calculations are considered. The time of onset of radiation pneumonitis occurs between 1 to 7 months after irradiation for 90% of the patients who developed pneumonitis with the peak incidence occurring at 2 at 3 months. No correlation was found between time of onset and the dose to lung over a dose range of 650 to 1250 rad.

  18. Systemic lupus erythematosus presenting as fulminant lupus pneumonitis: a rare case report.

    PubMed

    Aggarwal, H K; Jain, D; Mittal, A; Rao, A; Yadav, R K; Jain, P

    2016-01-01

    We report a case of 19 year-old female patient diagnosed as systemic lupus erythematosus (SLE) presented with fever and diffuse cutaneous lesions. During the hospital stay she had acute pneumonia, pleural effusion and respiratory failure, which required intensive care unit (ICU) care and mechanical ventilator support. A fulminant course of the disease, decreased values of complement levels and positive antinuclear antibodies (ANA) in pleural fluid and repeated negative sputum for acid-fast bacillus, blood cultures enabled diagnosis of fulminant lupus pneumonitis. Fulminant lupus pneumonitis is a rare but potentially life threatening complication of SLE. Management requires involvement of multiple specialties and rigorous efforts in reviving the patient. PMID:27339374

  19. Radiation pneumonitis and fibrosis: Mechanisms underlying its pathogenesis and implications for future research

    SciTech Connect

    Tsoutsou, Pelagia G.; Koukourakis, Michael I. . E-mail: targ@her.forthnet.gr

    2006-12-01

    Radiation pneumonitis and subsequent radiation pulmonary fibrosis are the two main dose-limiting factors when irradiating the thorax that can have severe implications for patients' quality of life. In this article, the current concepts about the pathogenetic mechanisms underlying radiation pneumonitis and fibrosis are presented. The clinical course of fibrosis, a postulated acute inflammatory stage, and a late fibrotic and irreversible stage are discussed. The interplay of cells and the wide variety of molecules orchestrating the immunologic response to radiation, their interactions with specific receptors, and the cascade of events they trigger are elucidated. Finally, the implications of this knowledge with respect to the therapeutic interventions are critically presented.

  20. Severe pneumonitis after fire eating.

    PubMed

    Franzen, Daniel; Kohler, Malcolm

    2012-01-01

    A 38-year-old, previously healthy fire eater presented with severe pneumonitis after incidental aspiration of an unquantifiable amount of petroleum. The chest CT revealed extensive pulmonary consolidations, and the laboratory results showed massively elevated inflammatory markers. An intravenous antibiotic treatment was started and, after improvement of symptoms and inflammatory markers, continued orally for a total of 3 weeks, despite negative results of blood cultures and urinary pneumococcal and legionella antigen tests. The patient's symptoms subsided completely, and a CT scan 10 weeks after the accident showed complete resolution of the lung consolidations. Aspiration of petroleum is associated with a severe inflammatory response of the lung, but if bacterial superinfection can be prevented with early antibiotic treatment, even a severe presentation of a fire eater's lung usually follows a benign course with complete recovery. PMID:22948995

  1. [Prevention of Perioperative Aspiration Pneumonitis].

    PubMed

    Fukuda, Kazuhiko

    2016-01-01

    To prevent perioperative aspiration pneumonitis, it is necessary to reduce the volume and acidity of gastric content. The guideline for preoperative fasting published by Japanese Society of Anesthesiologists recommends fasting from intake of clear fluids, breast milk and nonhuman milk at least 2h, 4h and 6h, respectively, before elective procedures requiring general anesthesia, regional anesthesia or sedation/analgesia. Gastrointestinal stimulants, histamine-2 receptor antagonists, proton pump inhibitors, antacids, antiemetics, anticholinergics are effective for reduction of the volume or acidity of gastric content. However, the routine preoperative use of these drugs to reduce the risk of pulmonary aspiration in patients who have no apparent increased risk for pulmonary aspiration is not recommended. PMID:27004383

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

    PubMed Central

    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

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

    PubMed

    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

  4. Public Health Consequences on Vulnerable Populations from Acute Chemical Releases

    PubMed Central

    Ruckart, Perri Zeitz; Orr, Maureen F.

    2008-01-01

    Data from a large, multi-state surveillance system on acute chemical releases were analyzed to describe the type of events that are potentially affecting vulnerable populations (children, elderly and hospitalized patients) in order to better prevent and plan for these types of incidents in the future. During 2003–2005, there were 231 events where vulnerable populations were within ¼ mile of the event and the area of impact was greater than 200 feet from the facility/point of release. Most events occurred on a weekday during times when day care centers or schools were likely to be in session. Equipment failure and human error caused a majority of the releases. Agencies involved in preparing for and responding to chemical emergencies should work with hospitals, nursing homes, day care centers, and schools to develop policies and procedures for initiating appropriate protective measures and managing the medical needs of patients. Chemical emergency response drills should involve the entire community to protect those that may be more susceptible to harm. PMID:21572842

  5. Cockatiel-induced hypersensitivity pneumonitis.

    PubMed Central

    McCluskey, James D; Haight, Robert R; Brooks, Stuart M

    2002-01-01

    Diagnosing an environmental or occupationally related pulmonary disorder often involves a process of elimination. Unlike commonly diagnosed conditions in other specialties, a cause-and-effect relationship may be implied, yet other factors such as temporality and biologic plausibility are lacking. Our patient was referred with a suspected work-related pulmonary disorder. For several years, she had suffered with dyspnea on exertion and repeated flulike illnesses. She worked at an automobile repair garage that performed a large number of emission tests, and there was concern that her workplace exposures were the cause of her symptoms. After a careful review of her history, physical examination, and laboratory testing, we came to the conclusion that she had hypersensitivity pneumonitis related to pet cockatiels in her home. Clinical points of emphasis include the importance of a complete environmental history and careful auscultation of the chest when performing the physical examination. In addition, we encountered an interesting physical diagnostic clue, a respiratory sound that assisted with the eventual diagnosis. PMID:12117652

  6. Update on lymphoid interstitial pneumonitis.

    PubMed

    Fishback, N; Koss, M

    1996-09-01

    Lymphoid interstitial pneumonitis (LIP) involves a clinicopathologic pattern of pulmonary disease characterized by diffuse interstitial reactive lymphoid infiltrates. In adults, it occurs most commonly in autoimmune diseases, such as Sjögren's syndrome (0.9% of these patients) and primary biliary cirrhosis, whereas in children it is usually seen in HIV infection. Dysproteinemias (hyper- and hypogammaglobulinemia) are found in more than 60% of patients. Children can show CD8-lymphocytosis in bronchoalveolar lavage fluid, lung tissue, peripheral blood, and salivary gland, associated with HLA-DR5 haplotype. Radiographically, most patients with LIP have reticulonodular infiltrates, with or without patchy areas of consolidation. CT scans can show both small nodular and ground glass patterns, patterns that are diagnostically nonspecific. Reduced lung volumes and diffusing capacities are consistent and sensitive indicators of disease in LIP. In an experimental model, diffusing capacity was the single most sensitive functional index of disease progression. Microscopically, LIP is part of a spectrum of pulmonary lymphoid proliferations, ranging from follicular bronchitis-bronchiolitis and pulmonary lymphoid hyperplasia (the latter in AIDS patients), proliferations largely limited to airways, to low-grade malignant lymphoma. These patterns may be difficult to differentiate from each other. It appears that LIP sometimes evolves to lymphoma; the frequency of this evolution is probably low but is difficult to assess because low-grade lymphomas may mimic LIP. A relatively high frequency of LIP patients have Epstein-Barr virus DNA in their lungs but not all patients with LIP show this finding, suggesting other possible etiologies. PMID:9363179

  7. Hypersensitivity pneumonitis from ordinary residential exposures.

    PubMed Central

    Apostolakos, M J; Rossmoore, H; Beckett, W S

    2001-01-01

    A previously healthy woman developed hypersensitivity pneumonitis of such severity that she required chronic systemic corticosteroid therapy for symptom control. Detailed investigation of her workplace and home environments revealed fungi in her typical suburban home, to which she had specific serum precipitating antibodies. Efforts to remove mold from the home were unsuccessful in relieving symptoms, and moving to another residence was the only intervention that allowed her to be withdrawn from corticosteroid therapy. Hypersensitivity pneumonitis is commonly associated with occupational or avocational exposures, such as moldy hay in farmers or bird antigen in bird breeders. We propose that hypersensitivity pneumonitis may occur in North America, as it does in Japan, from domestic exposures alone. PMID:11673130

  8. Radiation Recall Pneumonitis During Systemic Treatment With Everolimus.

    PubMed

    Clark, Douglas; Gauchan, Dron; Ramaekers, Ryan; Norvell, Max; Copur, Mehmet Sitki

    2014-01-01

    Radiation recall syndrome is an acute inflammatory reaction developing at anatomical sites of previously irradiated tissue, weeks to months after the completion of radiation therapy. The distribution pattern of inflammation typically involves, and remains limited to, the boundaries of prior radiation treatment fields. Several classical chemotherapy drugs have been reported to have the potential for causing radiation recall syndrome. With the increasing availability and expanding use of novel biologic and targeted therapy anticancer drugs, isolated reports of radiation recall syndrome secondary to this class of agents are starting to appear in the literature. We describe a case of everolimus-induced radiation recall pneumonitis in a patient with metastatic renal cell cancer. PMID:26629944

  9. Pneumocystis jiroveci pneumonitis complicating ruxolitinib therapy

    PubMed Central

    Lee, Samantha C; Feenstra, John; Georghiou, Paul R

    2014-01-01

    Ruxolitinib is a novel inhibitor of the Janus kinase (JAK) pathway that has become available for the treatment of myelofibrosis. There are increasing reports of opportunistic infections associated with ruxolitinib therapy. We present a case of Pneumocystis jiroveci pneumonitis complicating ruxolitinib therapy. Clinicians should consider the use of pneumocystis prophylaxis when using ruxolitinib. PMID:24891492

  10. Interstitial Pneumonitis from Treatment with Gemcitabine

    PubMed Central

    Poole, Brolin B.; Brockman, Megan M.; Byrd, Debbie C.

    2014-01-01

    Introduction: The use of gemcitabine may lead to numerous adverse effects ranging from mild to very severe, such as interstitial pneumonitis. The diagnosis of this complication is based on multiple laboratory findings, radiographic evidence, and high clinical suspicion. Presented is a case report of a patient who met these criteria and had onset consistent with drug-induced interstitial pneumonitis. Case Presentation: A 76-year-old White female was treated with gemcitabine for pancreatic cancer. Two months after the initiation of therapy, she was admitted to the hospital for worsening dyspnea and cough. High clinical suspicion, bilateral interstitial opacities on chest x-ray, worsening pulmonary status, and onset 2 months after initiation of therapy led to the diagnosis of gemcitabine-induced interstitial pneumonitis. Steroid therapy with prednisone was initiated, and the patient’s clinical symptoms and radiographic findings improved. Discussion: Gemcitabine-induced interstitial pneumonitis is well described in the literature. It is a rare but serious complication associated with gemcitabine therapy in which patients present with worsening dyspnea. Most patients only require supportive care and discontinuation of the drug for treatment, but in severe cases supplemental oxygen and steroid therapy must be used before resolution of symptoms. It is important to obtain an accurate medication history to evaluate for other potentially pulmonary toxic medications. Radiographic findings such as bilateral infiltrates should be completely resolved after therapy. Conclusion: Radiographic findings, clinical symptoms, and clinical suspicion can lead to early recognition of interstitial pneumonitis from gemcitabine. Physician awareness of this adverse effect and early recognition are keys to providing prompt treatment in resolving symptoms and decreasing mortality. PMID:25477616

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

    NASA Astrophysics Data System (ADS)

    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.

  12. Acute oral toxicity test of chemical compounds in silkworms.

    PubMed

    Usui, Kimihito; Nishida, Satoshi; Sugita, Takuya; Ueki, Takuro; Matsumoto, Yasuhiko; Okumura, Hidenobu; Sekimizu, Kazuhisa

    2016-02-01

    This study performed an acute oral toxicity test of 59 compounds in silkworms. These compounds are listed in OECD guidelines as standard substances for a cytotoxicity test, and median lethal dose (LD(50)) werecalculated for each compound. Acute oral LD(50) values in mammals are listed in OECD guidelines and acute oral LD(50) values in silkworms were determined in this study. R(2) for the correlation between LD(50) values in mammals and LD(50) values in silkworms was 0.66. In addition, the acute oral toxicity test in silkworms was performed by two different facilities, and test results from the facilities were highly reproducible. These findings suggest that an acute oral toxicity test in silkworms is a useful way to evaluate the toxicity of compounds in mammals. PMID:26971557

  13. Effect of Hypersensitivity Pneumonitis on the Pulmonary Defense Mechanisms of Guinea Pig Lungs

    PubMed Central

    Jakab, George J.; Green, Gareth M.

    1973-01-01

    Many edemagenic and consolidating inflammatory diseases, such as virus pneumonias, of the lung are complicated by bacterial infection. Previous literature has stressed that edema and consolidation may promote bacterial proliferation by interfering with phagocytosis. To test that hypothesis, lung defense mechanisms were studied in guinea pigs with tuberculin-induced hypersensitivity pneumonitis, a noninfectious edemagenic, and consolidating inflammatory disease. Pulmonary bactericidal activity and particle clearance were measured with a mixed aerosol of 32P-labeled Staphylococcus aureus and35S-labeled Proteus mirabilis. Hypersensitivity pneumonitis enhanced the bactericidal activity of the lung but had no effect on particle clearance despite the presence of consolidation and edema. These data indicate that altered host resistance to bacterial infection in acute inflammatory lung diseases can not be attributed to edema, inflammation, consolidation, changes in lung weight, etc., per se and that causes must be sought in functional changes in the bactericidal system of the lung rather than in specific histopathological changes. Images PMID:4632134

  14. Simultaneous interstitial pneumonitis and cardiomyopathy induced by venlafaxine* **

    PubMed Central

    Ferreira, Pedro Gonçalo; Costa, Susana; Dias, Nuno; Ferreira, António Jorge; Franco, Fátima

    2014-01-01

    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. PMID:25029655

  15. Unilateral radiation pneumonitis in sheep: Physiological changes and bronchoalveolar lavage

    SciTech Connect

    Tillman, B.F.; Loyd, J.E.; Malcolm, A.W.; Holm, B.A.; Brigham, K.L. )

    1989-03-01

    Radiation pneumonitis is a life-threatening result of therapeutic thoracic irradiation, yet its mechanisms are poorly understood. We studied the effects of unilateral lung irradiation (3,000 rad) in sheep from the immediate response to the later development of radiation pneumonitis. We defined radiation pneumonitis by its diagnostic clinical feature, radiographic infiltration of the irradiated zone with a straight margin corresponding to the radiation port. The immediate response in the few hours after irradiation was characterized by cough, labored respiration, hypoxemia (arterial PO{sub 2} decreased 19 Torr), mild pulmonary hypertension (pulmonary arterial pressure increased 20%), and lymphopenia. Hemodynamics and gas exchange returned to normal by day 2 but became abnormal again before or during radiation pneumonitis at 32 +/- 2 days. Respiratory distress, hypoxemia, and pulmonary hypertension recurred during radiation pneumonitis. Bronchoalveolar lavage during radiation pneumonitis contained increased neutrophils (19 +/- 4%, control = 7%), increased protein (0.27 +/- 0.1 g/dl, control = 0.12 +/- 0.03), and severely impaired ability to lower surface tension. Alveolar macrophages from both lungs during unilateral radiation pneumonitis exhibited impaired generation of superoxide after phorbol myristate (only a 30% increase). Normal control alveolar macrophages increased superoxide production after stimulation greater than 400%. We conclude that unilateral lung irradiation in sheep causes a mild immediate response followed by radiation pneumonitis at 1 mo. Unilateral radiation pneumonitis in this model is associated with ipsilateral neutrophilic alveolitis, increased bronchoalveolar lavage protein, and impaired surfactant function, as well as bilateral functional abnormalities of alveolar macrophages.

  16. Genetic Control of Weight Loss During Pneumonic Burkholderia pseudomallei Infection

    PubMed Central

    Emery, Felicia D.; Parvathareddy, Jyothi; Pandey, Ashutosh K.; Cui, Yan; Williams, Robert W.; Miller, Mark A.

    2014-01-01

    Burkholderia pseudomallei (Bp) is the causal agent of a high morbidity/mortality disease syndrome known as melioidosis. This syndrome can range from acute fulminate disease to chronic, local, and disseminated infections that are often difficult to treat because Bp exhibits resistance to many antibiotics. Bp is a prime candidate for use in biological warfare/terrorism and is classified as a Tier-1 Select Agent by HHS and APHIS. It is known that inbred mouse strains display a range of susceptibility to Bp and that the murine infection model is ideal for studying acute melioidosis. Here we exploit a powerful mouse genetics resource that consists of a large family of BXD type recombinant inbred strains, to perform genome-wide linkage analysis of the weight loss phenotype following pneumonic infection with Bp. We infected parental mice and 32 BXD strains with 50-100 CFU of Bp (strain 1026b) and monitored weight retention each day over an eleven-day time course. Using the computational tools in GeneNetwork, we performed genome-wide linkage analysis to identify an interval on chromosome 12 that appears to control the weight retention trait. We then analysed and ranked positional candidate genes in this interval, several of which have intriguing connections with innate immunity, calcium homeostasis, lipid transport, host cell growth and development, and autophagy. PMID:24687986

  17. Acetazolamide attenuates chemical-stimulated but not thermal-stimulated acute pain in mice

    PubMed Central

    Sun, Ya-jie; Chen, Ying; Pang, Chong; Wu, Ning; Li, Jin

    2014-01-01

    Aim: Acetazolamide (AZA), a carbonic anhydrase (CA) inhibitor, has been found to alleviate inflammatory and neuropathic pain in rats. In the present study, we investigated the effects of AZA on thermal- and chemical-stimulated acute pain in mice and the possible mechanisms underlying the effects. Methods: Five acute pain models based on thermal and chemical stimuli were established to investigate the effects of AZA on different types of nociception in mice. The antinociceptive effects of methazolamide (another CA inhibitor) and diazepam (a positive allosteric modulator of GABAA receptor) were also examined. The drugs were administered either intraperitoneally (ip) or intrathecally. Results: AZA (50–200 mg/kg, ip) did not produce analgesia in two thermal-stimulated acute pain models, ie, mouse tail-flick and hot-plate tests. In contrast, AZA (50–200 mg/kg, ip) dose-dependently reduced paw licking time in both capsaicin and formalin tests in mice. A similar result was observed in a mouse acetic acid-induced writhing test. However, AZA (10 nmol/mouse, intrathecally) did not produce significant analgesia in the 3 chemical-stimulated acute pain models. In addition, methazolamide (50–200 mg/kg, ip) and diazepam (0.25–1.0 mg/kg, ip) did not produce significant analgesia in either thermal- or chemical-stimulated acute pain. Conclusion: AZA produces analgesia in chemical-stimulated, but not thermal-stimulated acute pain in mice. The attenuation of chemical-stimulated acute pain by AZA may not be due to enhancement of GABAA receptor-mediated inhibition via inhibiting CA activity but rather a peripheral ion channel-related mechanism. PMID:24335844

  18. Yacht-maker's lung: A case of hypersensitivity pneumonitis in yacht manufacturing.

    PubMed

    Volkman, Kristen K; Merrick, James G; Zacharisen, Michael C

    2006-10-01

    We present a case of hypersensitivity pneumonitis in a 46-year-old female working at a yacht manufacturing company. She reported a 2-month history of progressive dyspnea, chest tightness, and daytime, nocturnal, and exertional cough in temporal relationship to work where she was exposed to chemicals involved in the manufacture of yachts. Treatment with systemic antibiotic therapy, inhaled bronchodilators, and inhaled corticosteroids provided minimal relief of symptoms. Spirometry revealed a restrictive defect and a chest x-ray demonstrated a diffuse interstitial pattern. She improved on oral corticosteroids and with avoidance of her work environment had resolution of her symptoms and normalization of her spirometry. Among the various chemicals the patient was exposed to, the most likely causative agents for her symptoms were dimethyl phthalate and styrene. Although the specific chemical or antigen could not be determined, the history and objective findings are consistent with occupational hypersensitivity pneumonitis. This represents a case of hypersensitivity pneumonitis related to the manufacture of yachts. PMID:17163087

  19. [Acute pneumonia caused by aspiration of hydrocarbons in a fire-eater].

    PubMed

    Vimercati, L; Lorusso, A; Bruno, S; Carrus, A; Cappello, S; Belfiore, A; Portincasa, P; Palasciano, G; Assennato, G

    2006-01-01

    Accidental aspiration of fuel in fire eaters can cause an acute chemical pneumonitis known as 'fire-eater's pneumonia". We report a case in a 29 year-old fire-eater. Six hours after aspiration of kerosene, he developed fever up to 39,5 degrees C, dyspnea, cough and chest pain. Chest radiograph showed infiltrates in the middle and lower parts of the lungs and left pleural effusion. He was treated with an antibiotic and antipiretic therapy and then with corticosteroids. The acute stage lasted four weeks and the patient recovered without sequelae within 3 months. Hazard related to main fuels used for fire eating is discussed. PMID:16805480

  20. Mouse models of acute, chemical itch and pain in humans

    PubMed Central

    LaMotte, Robert H.; Shimada, Steven G.; Sikand, Parul

    2011-01-01

    In psychophysical experiments, humans use different verbal responses to pruritic and algesic chemical stimuli to indicate the different qualities of sensation they feel. A major challenge for behavioral models in the mouse of chemical itch and pain in humans is to devise experimental protocols that provide the opportunity for the animal to exhibit a multiplicity of responses as well. One basic criterion is that chemicals that evoke primarily itch or pain in humans should elicit different types of responses when applied in the same way to the mouse. Meeting this criterion is complicated by the fact that the type of behavioral responses exhibited by the mouse depends in part on the site of chemical application such as the nape of the neck which evokes only scratching with the hind paw vs. the hind limb which elicits licking and biting. Here, we review to what extent mice behaviorally differentiate chemicals that elicit itch vs. pain in humans. PMID:21929688

  1. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure...

  2. Percutaneous needle lung aspiration for diagnosing pneumonitis in the patient with acquired immunodeficiency syndrome (AIDS).

    PubMed

    Wallace, J M; Batra, P; Gong, H; Ovenfors, C O

    1985-03-01

    Fourteen patients with acquired immunodeficiency syndrome (AIDS) or suspected AIDS underwent percutaneous needle lung aspiration (PNLA) for evaluation of 16 occurrences of acute pneumonitis. A 22-gauge spinal needle was passed 2 to 3 times in the area of greatest radiographic involvement under fluoroscopic guidance. The specimen was immediately placed on microscope slides for Gomori's methenamine silver and Papanicolaou staining. The needle was then flushed with sterile water for bacterial, Legionella, viral, mycobacterial, and fungal cultures, and for Legionella immunofluorescent staining. Diagnostic information was provided by 14 of the 16 procedures. Of 11 patients ultimately found to have P. carinii pneumonitis, PNLA specimens were diagnostic in 10 (91%). Infectious agents other than P. carinii also were identified by PNLA, including cytomegalovirus (4 cases), M. avium-intracellulare (1 case), and pyogenic bacteria (3 cases). Complications of PNLA were: pneumothorax in 7 cases (44%), 3 (19%) of which required chest tube evacuation; and minor hemoptysis (less than 50 ml) in 2. The PNLA can be a useful diagnostic procedure in the patient with AIDS and pneumonitis. It has the advantages of being less costly and time-consuming than fiberoptic bronchoscopy. It is, however, frequently complicated by pneumothorax, making it an inappropriate approach for patients with significant respiratory compromise. PMID:3872089

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

    PubMed

    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. PMID:26698952

  4. Acute toxicity of fire-control chemicals, nitrogenous chemicals, and surfactants to rainbow trout

    USGS Publications Warehouse

    Buhl, K.J.; Hamilton, S.J.

    2000-01-01

    Laboratory studies were conducted to determine the acute toxicity of three ammonia-based fire retardants (Fire-Trol LCA-F, Fire-Trol LCM-R, and Phos-Chek 259F), five surfactant-based fire-suppressant foams (FireFoam 103B, FireFoam 104, Fire Quench, ForExpan S, and Pyrocap B-136), three nitrogenous chemicals (ammonia, nitrate, and nitrite), and two anionic surfactants (linear alkylbenzene sulfonate [LAS] and sodium dodecyl sulfate [SDS]) to juvenile rainbow trout Oncorhynchus mykiss in soft water. The descending rank order of toxicity (96-h concentration lethal to 50% of test organisms [96-h LC50]) for the fire retardants was as follows: Phos-Chek 259F (168 mg/L) > Fire-Trol LCA-F (942 mg/L) = Fire-Trol LCM-R (1,141 mg/L). The descending rank order of toxicity for the foams was as follows: FireFoam 103B (12.2 mg/L) = FireFoam 104 (13.0 mg/L) > ForExpan S (21.8 mg/L) > Fire Quench (39.0 mg/L) > Pyrocap B-136 [156 mg/L). Except for Pyrocap B-136, the foams were more toxic than the fire retardants. Un-ionized ammonia (NH3; 0.125 mg/L as N) was about six times more toxic than nitrite (0.79 mg/L NO2-N) and about 13,300 times more toxic than nitrate (1,658 mg/L NO3-N). Linear alkylbenzene sulfonate (5.0 mg/L) was about five times more toxic than SDS (24.9 mg/L). Estimated total ammonia and NH3 concentrations at the 96-h LC50s of the fire retardants indicated that ammonia was the primary toxic component in these formulations. Based on estimated anionic surfactant concentrations at the 96-h LC50s of the foams and reference surfactants, LAS was intermediate in toxicity and SDS was less toxic to rainbow trout when compared with the foams. Comparisons of recommended application concentrations to the test results indicate that accidental inputs of these chemicals into streams require substantial dilutions (100-1,750-fold to reach concentrations nonlethal to rainbow trout.

  5. Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma

    SciTech Connect

    Allen, Aaron M. . E-mail: aallen@lroc.harvard.edu; Czerminska, Maria; Jaenne, Pasi A.; Sugarbaker, David J.; Bueno, Raphael; Harris, Jay R.; Court, Laurence; Baldini, Elizabeth H.

    2006-07-01

    Purpose: To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Women's Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy. Methods and Materials: The medical records of patients treated with IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily fractions. Treatment was delivered with a dynamic multileaf collimator using a sliding window technique. Eleven of 13 patients received heated intraoperative cisplatin chemotherapy (225 mg/m{sup 2}). Two patients received neoadjuvant intravenous cisplatin/pemetrexed, and 10 patients received adjuvant cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All patients received at least 2 cycles of intravenous chemotherapy. The contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more) of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy to 60 Gy. Statistical comparisons were done using two-sided t test. Results: Thirteen patients were treated with IMRT from December 2004 to September 2005. Six patients developed fatal pneumonitis after treatment. The median time from completion of IMRT to the onset of radiation pneumonitis was 30 days (range 5-57 days). Thirty percent of patients (4 of 13) developed acute Grade 3 nausea and vomiting. One patient developed acute Grade 3 thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or more) for the patients who developed pneumonitis was 17.6% (range, 15.3-22.3%), 15.2 Gy (range, 13.3-17 Gy), and 98.6% (range, 81-100%), respectively, as compared with 10.9% (range, 5.5-24.7%) (p = 0.08), 12.9 Gy (range, 8.7-16.9 Gy) (p = 0.07), and 90% (range

  6. Use of fish embryo toxicity tests for the prediction of acute fish toxicity to chemicals.

    PubMed

    Belanger, Scott E; Rawlings, Jane M; Carr, Gregory J

    2013-08-01

    The fish embryo test (FET) is a potential animal alternative for the acute fish toxicity (AFT) test. A comprehensive validation program assessed 20 different chemicals to understand intra- and interlaboratory variability for the FET. The FET had sufficient reproducibility across a range of potencies and modes of action. In the present study, the suitability of the FET as an alternative model is reviewed by relating FET and AFT. In total, 985 FET studies and 1531 AFT studies were summarized. The authors performed FET-AFT regressions to understand potential relationships based on physical-chemical properties, species choices, duration of exposure, chemical classes, chemical functional uses, and modes of action. The FET-AFT relationships are very robust (slopes near 1.0, intercepts near 0) across 9 orders of magnitude in potency. A recommendation for the predictive regression relationship is based on 96-h FET and AFT data: log FET median lethal concentration (LC50) = (0.989 × log fish LC50) - 0.195; n = 72 chemicals, r = 0.95, p < 0.001, LC50 in mg/L. A similar, not statistically different regression was developed for the entire data set (n = 144 chemicals, unreliable studies deleted). The FET-AFT regressions were robust for major chemical classes with suitably large data sets. Furthermore, regressions were similar to those for large groups of functional chemical categories such as pesticides, surfactants, and industrial organics. Pharmaceutical regressions (n = 8 studies only) were directionally correct. The FET-AFT relationships were not quantitatively different from acute fish-acute fish toxicity relationships with the following species: fathead minnow, rainbow trout, bluegill sunfish, Japanese medaka, and zebrafish. The FET is scientifically supportable as a rational animal alternative model for ecotoxicological testing of acute toxicity of chemicals to fish. PMID:23606235

  7. Acute toxicity testing of chemicals-Opportunities to avoid redundant testing and use alternative approaches.

    PubMed

    Creton, Stuart; Dewhurst, Ian C; Earl, Lesley K; Gehen, Sean C; Guest, Robert L; Hotchkiss, Jon A; Indans, Ian; Woolhiser, Michael R; Billington, Richard

    2010-01-01

    Assessment of the acute systemic oral, dermal, and inhalation toxicities, skin and eye irritancy, and skin sensitisation potential of chemicals is required under regulatory schemes worldwide. In vivo studies conducted to assess these endpoints can sometimes be associated with substantial adverse effects in the test animals, and their use should always be scientifically justified. It has been argued that while information obtained from such acute tests provides data needed to meet classification and labelling regulations, it is of limited value for hazard and risk assessments. Inconsistent application of in vitro replacements, protocol requirements across regions, and bridging principles also contribute to unnecessary and redundant animal testing. Assessment of data from acute oral and dermal toxicity testing demonstrates that acute dermal testing rarely provides value for hazard assessment purposes when an acute oral study has been conducted. Options to waive requirements for acute oral and inhalation toxicity testing should be employed to avoid unnecessary in vivo studies. In vitro irritation models should receive wider adoption and be used to meet regulatory needs. Global requirements for sensitisation testing need continued harmonisation for both substance and mixture assessments. This paper highlights where alternative approaches or elimination of tests can reduce and refine animal use for acute toxicity requirements. PMID:20144136

  8. COMPARATIVE ACUTE SENSITIVITY OF LARVAL TOPSMELT, , ATHERINOPS AFFINIS, AND INLAND SILVERSIDES, MENIDIA BERYLLINA, TO ELEVEN CHEMICALS

    EPA Science Inventory

    Larval topsmelt (Atherinops affinis) and inland Silversides (Menidia eryllina) were exposed in 96-hr static acute toxicity tests to eleven chemicals to determine the relative sensitivity of the two atherinid species. igh to low LC50 ratios for endosulfan, methoxychlor, carbopheno...

  9. A Case of Occupational Hypersensitivity Pneumonitis Associated with Trichloroethylene

    PubMed Central

    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 who was employed as a lead welder at a computer repair center. He was installing the capacitors on computer chip boards and had been wiped down with TCE. He was admitted to our hospital with complaints of dry coughs, night sweats, and weight losses for the past two months. HP due to TCE exposure was being suspected due to his occupational history, and the results of a video-associated thoracoscopic biopsy confirmed the suspicions. Symptoms have resolved after the steroid pulse therapy and his occupational change. TCE should be taken into consideration as a potential trigger of HP. Early recognition and avoidance of the TCE exposure in the future is important for the treatment of TCE induced HP. PMID:24624216

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

    PubMed Central

    Ishizuka, Masahiro; Miyazaki, Yasunari; Masuo, Masahiro; Suhara, Kozo; Tateishi, Tomoya; Yasui, Makito; Inase, Naohiko

    2015-01-01

    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. PMID:26367130

  11. Hypersensitivity pneumonitis in a high school teacher.

    PubMed

    Moniodis, A; Hamilton, T; Racila, E; Cockrill, B; McCunney, R

    2015-10-01

    Hypersensitivity pneumonitis (HP) is an inflammatory lung disease mediated by an immunological response to an inhaled antigen. Outbreaks of HP have been reported in industrial settings where manufacturing workers are exposed to water-based metalworking fluids (MWFs). Water-based MWFs promote growth of microorganisms and can be easily aerosolized and are thus potential aetiological agents of HP. We present a case of HP caused by exposure to water-based MWF in a vocational high school teacher. Culture of MWF used at his school grew Pseudomonas pseudoalcaligenes. This is the first known report of MWF-induced HP outside an industrial setting. The growth of Pseudomonas spp in this case recalls the earliest reports of the microbiology of MWF-induced HP and suggests that routine bacterial culture may be useful in the diagnosis of HP in workplaces without standard cleaning and biocide regulations. PMID:26136595

  12. Pneumonic Plague Outbreak, Northern Madagascar, 2011

    PubMed Central

    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

  13. [Hypersensitivity pneumonitis: Diagnostic criteria, treatment, prognosis and prevention].

    PubMed

    Jędrych, Małgorzata E; Szturmowicz, Monika; Bestry, Iwona; Kuś, Jan

    2016-01-01

    Hypersensitivity pneumonitis (HP) is caused by inhalation of environmental antigens. Farmers and bird keepers are most frequently affected by this desease. The HP diagnosis is based on clinical symptoms (cough, dyspnea) in a person exposed to environmental antigens, and the presence of characteristic changes in high resolution chest computed tomography (HRCT) (bilateral, mosaic, ground glass opacities in the middle and lower lung zones, ill-defined centrilobular nodules and the sign of air-trapping on expiration). This type of HRCT pattern is most frequently found in the patients with subacute HP. Bronchioloalveolar lavage fluid (BALF) examination is helpful in establishing the HP diagnosis, when the increased total number of cells, with the predominance of T lymphocytes (> 50%), and the increased number of neutrophils (> 3%) and mastocytes (> 1%) are found. The presence of specific serum precipitins increases the likelihood of HP. In case of atypical clinical presentation, lung biopsy is recommended. The diagnostic criterion of HP is the presence of ill-defined non-necrotising granulomas, after excluding other granulomatous lung diseases. The prevention and treatment of HP is based on the elimination of the antigen from the environment. Corticosteroids may contribute to the improvement in the acute and sub-acute form of the disease but their long term effectiveness is uncertain. The prognosis of HP patients is generally perceived as good, especially in those patients in whom antigen avoidance is possible. Nevertheless, in some patients progressive pulmonary fibrosis and development of severe respiratory insufficiency is observed. Med Pr 2016;67(4):517-527. PMID:27623832

  14. Cognitive influences on health symptoms from acute chemical exposure.

    PubMed

    Dalton, P

    1999-11-01

    Symptom reports, perceived adverse health effects, and public health concerns are increasingly precipitated by the perception of chemical odors. This study examined the interaction between health cognitions, odor perception, and symptom reports. A group of 180 healthy men and women were exposed to 1 of 3 ambient odors, normatively rated as healthful (methyl salicylate, or wintergreen), harmful (butanol or alcohol), and ambiguous (isobomyl acetate, or balsam), after receiving 1 of 3 odorant characterizations (harmful, healthful, and neutral). Individuals given a harmful bias reported significantly more health symptoms following exposure and more intense odor and irritation during exposure than did those given a neutral or healthful bias. The overall pattern of results suggests that many of the health-related effects of exposure to odorants are mediated not by a direct agency of odors but by cognitive variables, such as mental models of the relationship between environmental odors and health. PMID:10619531

  15. Clinical course of acute chemical lung injury caused by 3-chloropentafluoropene.

    PubMed

    Morita, Satomu; Takimoto, Takayuki; Kawahara, Kunimitsu; Nishi, Katsuji; lino, Morio

    2013-01-01

    Perfluoroallyl chloride (PFAC), a fluorine-containing compound, has very severe toxicity, but this toxicity is not well characterised. We report a fatal case of acute chemical lung injury caused by the inhalation of PFAC. A 39-year-old man, working at a chemical factory, inhaled PFAC gas and died 16 days later of acute lung injury with severe pneumothorax. We present his clinical course together with thoracic CT findings, autopsy and analysis of PFAC in blood and urine samples with gas chromatograph-mass spectrometry. Previously, a fatal case of PFAC was reported in 1981 but PFAC was not identified in any of the patient's samples. In our patient, we identified PFAC in both blood and urine samples. Our toxicological analysis may be used as a reference to detect PFAC toxicity in the future. Our study should be helpful for diagnosing lung injury induced by a highly toxic gas, such as PFAC. PMID:24311414

  16. Clinical course of acute chemical lung injury caused by 3-chloropentafluoropene

    PubMed Central

    Morita, Satomu; Takimoto, Takayuki; Kawahara, Kunimitsu; Nishi, Katsuji

    2013-01-01

    Perfluoroallyl chloride (PFAC), a fluorine-containing compound, has very severe toxicity, but this toxicity is not well characterised. We report a fatal case of acute chemical lung injury caused by the inhalation of PFAC. A 39-year-old man, working at a chemical factory, inhaled PFAC gas and died 16 days later of acute lung injury with severe pneumothorax. We present his clinical course together with thoracic CT findings, autopsy and analysis of PFAC in blood and urine samples with gas chromatograph–mass spectrometry. Previously, a fatal case of PFAC was reported in 1981 but PFAC was not identified in any of the patient's samples. In our patient, we identified PFAC in both blood and urine samples. Our toxicological analysis may be used as a reference to detect PFAC toxicity in the future. Our study should be helpful for diagnosing lung injury induced by a highly toxic gas, such as PFAC. PMID:24311414

  17. Primary chemical and physical characterization of acute toxic components in wastewaters

    SciTech Connect

    Svenson, A.; Linlin, Z.; Kaj, L. )

    1992-10-01

    A chemical and physical primary characterization work sheet was developed based on the Microtox test, a bacterial bioluminescence system used as a rapid estimate of acute aquatic toxic effects. Measurements of the variation in light reduction upon different pretreatments provided information about the chemical and physical properties of the main toxic component(s) in test wastewater samples. This primary characterization of a wastewater sample was performed within 1 day. Tests of pure toxic chemical compounds and wastewaters with known and unknown primary toxicants are presented. Outlines to the chemical analysis and identification of toxic components may be deduced from the primary characterization. The provisional characterization may also provide information on wastewater treatment techniques.

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

    SciTech Connect

    Kharofa, Jordan; Cohen, Eric P.; Tomic, Rade; Xiang Qun; Gore, Elizabeth

    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. Acute and developmental behavioral effects of flame retardants and related chemicals in zebrafish

    PubMed Central

    Jarema, Kimberly A.; Hunter, Deborah L.; Shaffer, Rachel M.; Behl, Mamta; Padilla, Stephanie

    2016-01-01

    As polybrominated diphenyl ethers are phased out, numerous compounds are emerging as potential replacement flame retardants for use in consumer and electronic products. Little is known, however, about the neurobehavioral toxicity of these replacements. This study evaluated the neurobehavioral effects of acute or developmental exposure to t-butylphenyl diphenyl phosphate (BPDP), 2-ethylhexyl diphenyl phosphate (EHDP), isodecyl diphenyl phosphate (IDDP), isopropylated phenyl phosphate (IPP), tricresyl phosphate (TMPP; also abbreviated TCP), triphenyl phosphate (TPHP; also abbreviated TPP), tetrabromobisphenol A (TBBPA), tris (2-chloroethyl) phosphate (TCEP), tris (1,3-dichloroisopropyl) phosphate (TDCIPP; also abbreviated TDCPP), tri-o-cresyl phosphate (TOCP), and 2,2-,4,4′-tetrabromodiphenyl ether (BDE-47) in zebrafish (Danio rerio) larvae. Larvae (n ≈ 24 per dose per compound) were exposed to test compounds (0.4–120 µM) at sub-teratogenic concentrations either developmentally or acutely, and locomotor activity was assessed at 6 days post fertilization. When given developmentally, all chemicals except BPDP, IDDP and TBBPA produced behavioral effects. When given acutely, all chemicals produced behavioral effects, with TPHP, TBBPA, EHDP, IPP, and BPDP eliciting the most effects at the most concentrations. The results indicate that these replacement flame retardants may have developmental or pharmacological effects on the vertebrate nervous system. PMID:26348672

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

    SciTech Connect

    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.

  1. [Environmental causes of the distal airways disease. Hypersensitivity pneumonitis and rare causes].

    PubMed

    Dalphin, J-C; Didier, A

    2013-10-01

    Hypersensitivity pneumonitis is one of the most frequent causes of distal airways disease. It is associated with inflammation of the bronchioles, predominantly by lymphocytic infiltrates, and with granuloma formation causing bronchial obstruction. This inflammation explains the clinical manifestations and the airways obstruction seen on pulmonary function tests, most often in the distal airways but proximal in almost 20%. CT scan abnormalities reflect the lymphocytic infiltrates and air trapping and, in some cases, the presence of emphysema. Bronchiolitis induced by chronic inhalation of mineral particles or acute inhalation of toxic gases (such as NO2) are other examples of small airways damage due to environmental exposure. The pathophysiological mechanisms are different and bronchiolar damage is either exclusive or predominant. Bronchiolitis induced by tobacco smoke exposure, usually classified as interstitial pneumonitis, is easily diagnosed thanks to broncho-alveolar lavage. Its prognosis is linked to the other consequences of tobacco smoke exposure including respiratory insufficiency. Finally, the complex lung exposure observed in some rare cases (such as the World Trade Center fire or during wars) may lead to a less characteristic pattern of small airways disease. PMID:24182653

  2. Efficacy of lasalocid against murine Pneumocystis carinii pneumonitis.

    PubMed Central

    OZ, H S; Hughes, W T; Rehg, J E

    1997-01-01

    The efficacy of the ionophore lasalocid against Pneumocystis carinii pneumonitis in corticosteroid-immunosuppressed Sprague-Dawley rats was investigated. Lasalocid was effective in the prevention of the pneumonitis in a dose-dependent manner. At dosages of 0, 5, 10, and 20 mg/kg/day, P. carinii infection rates were 92, 60, 20, and 0%, respectively, during dexamethasone immunosuppression. Also, lasalocid compared favorably with other drugs known to have anti-P. carinii activity, including trimethoprim-sulfamethoxazole, atovaquone, and dapsone-trimethoprim. PMID:8980779

  3. Development of a QSAR for worst case estimates of acute toxicity of chemically reactive compounds.

    PubMed

    Freidig, A P; Dekkers, S; Verwei, M; Zvinavashe, E; Bessems, J G M; van de Sandt, J J M

    2007-05-15

    Future EU legislations enforce a fast hazard and risk assessment of thousands of existing chemicals. If conducted by means of present data requirements, this assessment will use a huge number of test animals and will be neither cost nor time effective. The purpose of the current research was to develop methods to increase the acceptability of in vitro data for classification and labelling regarding acute toxicity. For this purpose, a large existing database containing in vitro and in vivo data was analysed. For more than 300 compounds in the database, relations between in vitro cytotoxicity and rat or mouse intravenous and oral in vivo LD50 values were re-evaluated and the possibilities for definition of mechanism based chemical subclasses were investigated. A high in vitro-in vivo correlation was found for chemicals classified as irritants. This can be explained by a shared unspecific cytotoxicity of these compounds which will act as the predominant mode of action for both endpoints, irritation and acute toxicity. For this subclass, which covered almost 40% of all compounds in the database, the LD50 values after intravenous dosing could be predicted with high accuracy. A somewhat lower accuracy was found for the prediction of oral LD50 values based on in vitro cytotoxicity data. Based on this successful correlation, a classification and labelling scheme was developed, that includes a hazard based definition of the applicability domain (irritants) and a prediction of the labelling of compounds for their acute iv and oral toxicity. The scheme was tested by an external validation. PMID:17462838

  4. Assessing contaminant sensitivity of endangered and threatened aquatic species: Part I. Acute toxicity of five chemicals

    USGS Publications Warehouse

    Dwyer, F.J.; Mayer, F.L.; Sappington, L.C.; Buckler, D.R.; Bridges, C.M.; Greer, I.E.; Hardesty, D.K.; Henke, C.E.; Ingersoll, C.G.; Kunz, J.L.; Whites, D.W.; Augspurger, T.; Mount, D.R.; Hattala, K.; Neuderfer, G.N.

    2005-01-01

    Assessment of contaminant impacts to federally identified endangered, threatened and candidate, and state-identified endangered species (collectively referred to as "listed" species) requires understanding of a species' sensitivities to particular chemicals. The most direct approach would be to determine the sensitivity of a listed species to a particular contaminant or perturbation. An indirect approach for aquatic species would be application of toxicity data obtained from standard test procedures and species commonly used in laboratory toxicity tests. Common test species (fathead minnow, Pimephales promelas; sheepshead minnow, Cyprinodon variegatus; and rainbow trout, Oncorhynchus mykiss) and 17 listed or closely related species were tested in acute 96-hour water exposures with five chemicals (carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin) representing a broad range of toxic modes of action. No single species was the most sensitive to all chemicals. For the three standard test species evaluated, the rainbow trout was more sensitive than either the fathead minnow or sheepshead minnow and was equal to or more sensitive than listed and related species 81% of the time. To estimate an LC50 for a listed species, a factor of 0.63 can be applied to the geometric mean LC50 of rainbow trout toxicity data, and more conservative factors can be determined using variance estimates (0.46 based on 1 SD of the mean and 0.33 based on 2 SD of the mean). Additionally, a low- or no-acute effect concentration can be estimated by multiplying the respective LC50 by a factor of approximately 0.56, which supports the United States Environmental Protection Agency approach of multiplying the final acute value by 0.5 (division by 2). When captive or locally abundant populations of listed fish are available, consideration should be given to direct testing. When direct toxicity testing cannot be performed, approaches for developing protective measures using common test

  5. Chemical identification and acute biotoxicity assessment of gaseous chlorobenzene photodegradation products.

    PubMed

    Wang, Can; Xi, Jin-ying; Hu, Hong-ying

    2008-11-01

    In order to evaluate the ecological safety and feasibility of UV photodegradation processes for the treatment of halogenated aromatic hydrocarbons, the chemical composition and acute biotoxicity of gaseous chlorobenzene photodegradation products were investigated. Results showed that the main products of chlorobenzene photodegradation included hydrochloric acid, acetic acid, formic acid, phenol and chlorophenol. Roughly 64% of the removed chlorobenzene was converted into phenol, making it the most significant product formed. The types of byproducts suggested that two distinct reaction pathways might compete during the photodegradation process. Interestingly, it appeared that one of these pathways did not involve the direct photocatalytic oxidation of chlorobenzene. An acute biotoxicity assay measuring the inhibition of bioluminescence indicated that gaseous exhaust with overall higher toxicity was emitted after UV irradiation. The acute toxicity of the UV reactor exhaust gas was as high as EC(50)=13.5mg-Zn(2+)m(-3-)-gas. The increased toxicity mainly resulted from the conversion of chlorobenzene to more soluble toxic products and ozone production during the photodegradation process. PMID:18774585

  6. Predicting acute aquatic toxicity of structurally diverse chemicals in fish using artificial intelligence approaches.

    PubMed

    Singh, Kunwar P; Gupta, Shikha; Rai, Premanjali

    2013-09-01

    The research aims to develop global modeling tools capable of categorizing structurally diverse chemicals in various toxicity classes according to the EEC and European Community directives, and to predict their acute toxicity in fathead minnow using set of selected molecular descriptors. Accordingly, artificial intelligence approach based classification and regression models, such as probabilistic neural networks (PNN), generalized regression neural networks (GRNN), multilayer perceptron neural network (MLPN), radial basis function neural network (RBFN), support vector machines (SVM), gene expression programming (GEP), and decision tree (DT) were constructed using the experimental toxicity data. Diversity and non-linearity in the chemicals' data were tested using the Tanimoto similarity index and Brock-Dechert-Scheinkman statistics. Predictive and generalization abilities of various models constructed here were compared using several statistical parameters. PNN and GRNN models performed relatively better than MLPN, RBFN, SVM, GEP, and DT. Both in two and four category classifications, PNN yielded a considerably high accuracy of classification in training (95.85 percent and 90.07 percent) and validation data (91.30 percent and 86.96 percent), respectively. GRNN rendered a high correlation between the measured and model predicted -log LC50 values both for the training (0.929) and validation (0.910) data and low prediction errors (RMSE) of 0.52 and 0.49 for two sets. Efficiency of the selected PNN and GRNN models in predicting acute toxicity of new chemicals was adequately validated using external datasets of different fish species (fathead minnow, bluegill, trout, and guppy). The PNN and GRNN models showed good predictive and generalization abilities and can be used as tools for predicting toxicities of structurally diverse chemical compounds. PMID:23764236

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

    PubMed

    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. PMID:24658888

  8. Parasitic infestation of lung: An unusual cause of interstitial pneumonitis

    PubMed Central

    Shah, Parth; Kate, Arvind H; Nester, Nora; Patole, Kamlakar; Leuppi, Joerg D; Chhajed, Prashant N

    2016-01-01

    Parasite infections are increasing worldwide due to increasing migration and traveling. Parasitic infections can affect lungs and present as a focal or diffuse lung diseases. High index of suspicion and detailed history are most important. We present a case of interstitial pneumonitis caused by parasite infestation, which was diagnosed on transbronchial lung biopsy. PMID:27051117

  9. Fatal Pneumonitis Induced by Oxaliplatin: Description of Three Cases

    PubMed Central

    Pontes, L.B.; Armentano, D.P.D.; Soares, A.; Gansl, R.C.

    2012-01-01

    We describe 3 fatal cases of interstitial pneumonitis rapidly evolving to pulmonary fibrosis and death after the administration of oxaliplatin as part of the FOLFOX regimen. Due to the widespread use of oxaliplatin in oncology, clinicians should be aware of the risk and severity of oxalipatin-induced interstitial pneumonia. PMID:22539922

  10. Quantile regression model for a diverse set of chemicals: application to acute toxicity for green algae.

    PubMed

    Villain, Jonathan; Lozano, Sylvain; Halm-Lemeille, Marie-Pierre; Durrieu, Gilles; Bureau, Ronan

    2014-12-01

    The potential of quantile regression (QR) and quantile support vector machine regression (QSVMR) was analyzed for the definitions of quantitative structure-activity relationship (QSAR) models associated with a diverse set of chemicals toward a particular endpoint. This study focused on a specific sensitive endpoint (acute toxicity to algae) for which even a narcosis QSAR model is not actually clear. An initial dataset including more than 401 ecotoxicological data for one species of algae (Selenastrum capricornutum) was defined. This set corresponds to a large sample of chemicals ranging from classical organic chemicals to pesticides. From this original data set, the selection of the different subsets was made in terms of the notion of toxic ratio (TR), a parameter based on the ratio between predicted and experimental values. The robustness of QR and QSVMR to outliers was clearly observed, thus demonstrating that this approach represents a major interest for QSAR associated with a diverse set of chemicals. We focused particularly on descriptors related to molecular surface properties. PMID:25431186

  11. Elevation in Exhaled Nitric Oxide Predicts for Radiation Pneumonitis

    SciTech Connect

    Guerrero, Thomas; Martinez, Josue; McCurdy, Matthew R.; Wolski, Michael; McAleer, Mary Francis

    2012-02-01

    Purpose: Radiation pneumonitis is a major toxicity after thoracic radiotherapy (RT), with no method available to accurately predict the individual risk. This was a prospective study to evaluate exhaled nitric oxide as a predictive biomarker for radiation pneumonitis in esophageal cancer patients. Patients and Methods: A total of 34 patients prescribed neoadjuvant chemoradiotherapy for esophageal cancer were enrolled in the present trial. Each patient underwent respiratory surveys and exhaled nitric oxide (NO) measurements before, at the end of, and 1 to 2 months after completing RT. Pneumonitis toxicity was scored using the Common Terminology Criteria for Adverse Events, version 4.0. The demographics, dosimetric factors, and exhaled NO levels were evaluated for correlation with symptomatic patients (scores {>=}2). Results: Of the 34 patients, 28 were evaluable. All had received 50.4 Gy RT with concurrent chemotherapy. The pneumonitis toxicity score was Grade 3 for 1, Grade 2 for 3, Grade 1 for 7, and Grade 0 for 17. The dosimetric factors were not predictive of symptoms. The mean exhaled NO level measured before, at completion, and at restaging was 17.3 {+-} 8.5 (range, 5.5-36.7), 16.0 {+-} 14.2 (range, 5.8-67.7), and 14.7 {+-} 6.2 (range, 5.5-28.0) parts per billion, respectively. The ratio of exhaled NO at the end of RT vs. before treatment was 3.4 (range, 1.7-6.7) for the symptomatic and 0.8 (range, 0.3-1.3) for the asymptomatic (p = .0017) patients. The elevation in exhaled NO preceded the peak symptoms by 33 days (range, 21-50). The interval to peak symptoms was inversely related to the exhaled NO elevation. Conclusions: Elevations in exhaled NO at the end of RT was found to predict for radiation pneumonitis symptoms.

  12. Radiological and Clinical Pneumonitis After Stereotactic Lung Radiotherapy: A Matched Analysis of Three-Dimensional Conformal and Volumetric-modulated Arc Therapy Techniques

    SciTech Connect

    Palma, David A.; Senan, Suresh; Haasbeek, Cornelis J.A.; Verbakel, Wilko F.A.R.; Vincent, Andrew; Lagerwaard, Frank

    2011-06-01

    Purpose: Lung fibrosis is common after stereotactic body radiotherapy (SBRT) for lung tumors, but the influence of treatment technique on rates of clinical and radiological pneumonitis is not well described. After implementing volumetric modulated arc therapy (RapidArc [RA]; Varian Medical Systems, Palo Alto, CA) for SBRT, we scored the early pulmonary changes seen with arc and conventional three-dimensional SBRT (3D-CRT). Methods and Materials: Twenty-five SBRT patients treated with RA were matched 1:2 with 50 SBRT patients treated with 3D-CRT. Dose fractionations were based on a risk-adapted strategy. Clinical pneumonitis was scored using Common Terminology Criteria for Adverse Events version 3.0. Acute radiological changes 3 months posttreatment were scored by three blinded observers. Relationships among treatment type, baseline factors, and outcomes were assessed using Spearman's correlation, Cochran-Mantel-Haenszel tests, and logistic regression. Results: The RA and 3D-CRT groups were well matched. Forty-three patients (57%) had radiological pneumonitis 3 months after treatment. Twenty-eight patients (37%) had computed tomography (CT) findings of patchy or diffuse consolidation, and 15 patients (20%) had ground-glass opacities only. Clinical pneumonitis was uncommon, and no differences were seen between 3D-CRT vs. RA patients in rates of grade 2/3 clinical pneumonitis (6% vs. 4%, respectively; p = 0.99), moderate/severe radiological changes (24% vs. 36%, respectively, p = 0.28), or patterns of CT changes (p = 0.47). Radiological severity scores were associated with larger planning target volumes (p = 0.09) and extended fractionation (p = 0.03). Conclusions: Radiological changes after lung SBRT are common with both approaches, but no differences in early clinical or radiological findings were observed after RA. Longer follow-up will be required to exclude late changes.

  13. The difference between temperate and tropical saltwater species' acute sensitivity to chemicals is relatively small.

    PubMed

    Wang, Zhen; Kwok, Kevin W H; Lui, Gilbert C S; Zhou, Guang-Jie; Lee, Jae-Seong; Lam, Michael H W; Leung, Kenneth M Y

    2014-06-01

    Due to a lack of saltwater toxicity data in tropical regions, toxicity data generated from temperate or cold water species endemic to North America and Europe are often adopted to derive water quality guidelines (WQG) for protecting tropical saltwater species. If chemical toxicity to most saltwater organisms increases with water temperature, the use of temperate species data and associated WQG may result in under-protection to tropical species. Given the differences in species composition and environmental attributes between tropical and temperate saltwater ecosystems, there are conceivable uncertainties in such 'temperate-to-tropic' extrapolations. This study aims to compare temperate and tropical saltwater species' acute sensitivity to 11 chemicals through a comprehensive meta-analysis, by comparing species sensitivity distributions (SSDs) between the two groups. A 10 percentile hazardous concentration (HC10) is derived from each SSD, and then a temperate-to-tropic HC10 ratio is computed for each chemical. Our results demonstrate that temperate and tropical saltwater species display significantly different sensitivity towards all test chemicals except cadmium, although such differences are small with the HC10 ratios ranging from 0.094 (un-ionised ammonia) to 2.190 (pentachlorophenol) only. Temperate species are more sensitive to un-ionised ammonia, chromium, lead, nickel and tributyltin, whereas tropical species are more sensitive to copper, mercury, zinc, phenol and pentachlorophenol. Through comparison of a limited number of taxon-specific SSDs, we observe that there is a general decline in chemical sensitivity from algae to crustaceans, molluscs and then fishes. Following a statistical analysis of the results, we recommend an extrapolation factor of two for deriving tropical WQG from temperate information. PMID:24289976

  14. Acute toxicity of eight oil spill response chemicals to temperate, boreal, and Arctic species.

    PubMed

    Hansen, Bjørn Henrik; Altin, Dag; Bonaunet, Kristin; Overjordet, Ida Beathe

    2014-01-01

    The objectives of this study were to (1) determine the acute toxicity of selected shoreline washing agents (SWA) and dispersants, and (2) assess interspecies differences in sensitivity to the products. Eight shoreline washing agents (Hela saneringsvæske, Bios, Bioversal, Absorrep K212, and Corexit 9580) and chemical dispersants (Corexit 9500, Dasic NS, and Gamlen OD4000) were tested on five marine species, algae Skeletonema costatum, planktonic copepod species Acartia tonsa (temperate species), Calanus finmarchicus (boreal species) and Calanus glacialis (Arctic species), and benthic amphipod Corophium volutator. For most products, A. tonsa was the most sensitive species, whereas C. volutator was the least sensitive; however, these species were exposed through different media (water/sediment). In general, all copepod species displayed a relatively similar sensitivity to all products. However, A. tonsa was somewhat more sensitive than other copepods to most of the tested products. Thus, A. tonsa appears to be a candidate species for boreal and Arctic copepods for acute toxicity testing, and data generated on this species may be used as to provide conservative estimates. The benthic species (C. volutator) had a different sensitivity pattern relative to pelagic species, displaying higher sensitivity to solvent-based SWA than to water-based SWA. Comparing product toxicity, the dispersants were in general most toxic while the solvent-based SWA were least toxic to pelagic species. PMID:24754387

  15. Chemical composition, protoscolicidal effects and acute toxicity of Pistacia atlantica Desf. fruit extract.

    PubMed

    Mahmoudvand, Hossein; Kheirandish, Farnaz; Ghasemi Kia, Mehdi; Tavakoli Kareshk, Amir; Yarahmadi, Mohammad

    2016-05-01

    The present study was designed to evaluate the chemical composition and scolicidal effects of Pistacia atlantica Desf. extract against protoscoleces of hydatid cysts and its acute toxicity in mice model. Various concentrations of the methanolic extract (5-50 mg/mL) were used for 10-60 min. Viability of protoscoleces was confirmed using eosin exclusion test (0.1%). Acute toxicity was also determined in mice model. The main components were β-myrcene (41.4%), α-pinene (32.48%) and limonene (4.66%). Findings demonstrated that P. atlantica extract at the concentrations of 25 and 50 mg/mL after 20 and 10 min of exposure killed 100% protoscoleces. The LD50 of the intraperitoneal injection of the P. atlantica methanolic extract was 2.43 g/kg and the maximum non-fatal dose was 1.66 g/kg. Obtained results showed the potential of P. atlantica extract as a natural source with no significant toxicity for the production of new scolicidal agent to use in hydatid cyst surgery. PMID:26252652

  16. Challenges in defining radiation pneumonitis in patients with lung cancer

    SciTech Connect

    Kocak, Zafer; Evans, Elizabeth S.; Zhou Sumin; Miller, Keith L.; Folz, Rodney J.; Shafman, Timothy D.; Marks, Lawrence B. . E-mail: marks@radonc.duke.edu

    2005-07-01

    Purpose: To assess the difficulty of assigning a definitive clinical diagnosis of radiation (RT)-induced lung injury in patients irradiated for lung cancer. Methods: Between 1991 and 2003, 318 patients were enrolled in a prospective study to evaluate RT-induced lung injury. Only patients with lung cancer who had a longer than 6-month follow-up (251 patients) were considered in the current analysis. Of these, 47 of 251 patients had Grade {>=}2 (treated with steroids) increasing shortness of breath after RT, thought possibly consistent with pneumonitis/fibrosis. The treating physician, and one to three additional reviewing physicians, evaluated the patients or their medical records, or both. The presence or absence of confounding clinical factors that made the diagnosis of RT-induced uncertain lung injury were recorded. Results: Thirty-one of 47 patients (66%) with shortness of breath had 'classic' pneumonitis, i.e., they responded to steroids and had a definitive diagnosis of pneumonitis. In 13 of 47 patients (28%), the diagnosis of RT-induced toxicity was confounded by possible infection; exacerbation of preexisting lung disease (chronic obstructive pulmonary disease); tumor regrowth/progression; and cardiac disease in 6, 8, 5, and 1 patients, respectively (some of the patients had multiple confounding factors and were counted more than once). An additional 3 patients (6%) had progressive shortness of breath and an overall clinical course more consistent with fibrosis. All 3 had evidence of bronchial stenosis by bronchoscopy. Conclusions: Scoring of radiation pneumonitis was challenging in 28% of patients treated for lung cancer owing to confounding medical conditions. Recognition of this uncertainty is needed and may limit our ability to understand RT-induced lung injury.

  17. Occupational hypersensitivity pneumonitis in a smelter exposed to zinc fumes

    SciTech Connect

    Ameille, J.; Brechot, J.M.; Brochard, P.; Capron, F.; Dore, M.F. )

    1992-03-01

    A smelter exposed to zinc fumes reported severe recurrent episodes of cough, dyspnea and fever. Bronchoalveolar lavage showed a marked increase in lymphocytes count with predominance of CD8 T-lymphocytes. Presence of zinc in alveolar macrophages was assessed by analytic transmission electron microscopy. This is the first case of recurrent bronchoalveolitis related to zinc exposure in which the clinical picture and BAL results indicate a probable hypersensitivity pneumonitis.

  18. Acute and long-term biological effects of mechanically and chemically dispersed oil on lumpsucker (Cyclopterus lumpus).

    PubMed

    Frantzen, Marianne; Hansen, Bjørn Henrik; Geraudie, Perrine; Palerud, Jocelyn; Falk-Petersen, Inger-Britt; Olsen, Gro H; Camus, Lionel

    2015-04-01

    Concentration dependent differences in acute and long-term effects of a 48 h exposure to mechanically or chemically dispersed crude oil were assessed on juvenile lumpsucker (Cyclopterus lumpus). Acute or post-exposure mortality was only observed at oil concentrations representing higher concentrations than reported after real oil spills. Acute mortality was more apparent in chemically than mechanically dispersed oil treatments whereas comparable EC50s were observed for narcosis. There was a positive correlation between EROD activity and muscle PAH concentration for the lower oil concentrations whereas higher concentrations inhibited the enzyme activity. The incidence of gill tissue lesions was low with no difference between dispersion methods or oil concentrations. A concentration dependent decrease in swimming- and feeding behavior and in SGR was observed at the start of the post-exposure period, but with no differences between corresponding oil treatments. Three weeks post-exposure, fish from all treatments showed as high SGR as the control fish. PMID:25637877

  19. Interstitial pneumonitis after bone marrow transplantation. Assessment of risk factors

    SciTech Connect

    Weiner, R.S.; Bortin, M.M.; Gale, R.P.; Gluckman, E.; Kay, H.E.; Kolb, H.J.; Hartz, A.J.; Rimm, A.A.

    1986-02-01

    Data from 932 patients with leukemia who received bone marrow transplants were analyzed to determine factors associated with an increased risk of developing interstitial pneumonitis. Interstitial pneumonitis developed in 268 patients for a 2-year actuarial incidence of 35 +/- 4% (SD) and with a mortality rate of 24%. Six factors were associated with an increased risk: use of methotrexate rather than cyclosporine after transplantation (relative risk, 2.3; p less than 0.0002); older age (relative risk, 2.1; p less than 0.0001); presence of severe graft-versus-host disease (relative risk, 1.9; p less than 0.003); long interval from diagnosis to transplantation (relative risk, 1.6; p less than 0.002); performance ratings before transplantation of less than 100% (relative risk, 2.1; p less than 0.0001); and high dose-rates of irradiation in patients given methotrexate after transplantation (relative risk, 3.2; p less than 0.03). The risk of developing interstitial pneumonitis ranged from 8% in patients with none of these adverse risk factors to 94% in patients with all six. These findings may help to identify patients at high risk for this complication.

  20. Where Asthma and Hypersensitivity Pneumonitis Meet and Differ

    PubMed Central

    Bogaert, Pieter; Tournoy, Kurt G.; Naessens, Thomas; Grooten, Johan

    2009-01-01

    Asthma is a type-I allergic airway disease characterized by Th2 cells and IgE. Episodes of bronchial inflammation, eosinophilic in nature and promoting bronchoconstriction, may become chronic and lead to persistent respiratory symptoms and irreversible structural airway changes. Representative mostly of mild to moderate asthma, this clinical definition fails to account for the atypical and often more severe phenotype found in a considerable proportion of asthmatics who have increased neutrophil cell counts in the airways as a distinguishing trait. Neutrophilic inflammation is a hallmark of another type of allergic airway pathology, hypersensitivity pneumonitis. Considered as an immune counterpart of asthma, hypersensitivity pneumonitis is a prototypical type-III allergic inflammatory reaction involving the alveoli and lung interstitium, steered by Th1 cells and IgG and, in its chronic form, accompanied by fibrosis. Although pathologically very different and commonly approached as separate disorders, as discussed in this review, clinical studies as well as data from animal models reveal undeniable parallels between both airway diseases. Danger signaling elicited by the allergenic agent or by accompanying microbial patterns emerges as critical in enabling immune sensitization and in determining the type of sensitization and ensuing allergic disease. On this basis, we propose that asthma allergens cause severe noneosinophilic asthma because of sensitization in the presence of hypersensitivity pneumonitis-promoting danger signaling. PMID:19074616

  1. The effects of fasting on the acute oral toxicity of nine chemicals in the rat.

    PubMed

    Dashiell, O L; Kennedy, G L

    1984-12-01

    Nine chemicals, with a range from extremely to slightly toxic, were used to measure the oral LD50 in both fasted (24-h) and non-fasted rats. Each chemical was tested as a solution or suspension in corn oil, responses within 14 days post-treatment were evaluated, and LD50S were calculated. Hexachlorophene was more toxic in non-fasted rats. The LD50 values for tetraethyl lead, methomyl and hexamethylenediamine were essentially the same in both fasted and non-fasted rats. Adiponitrile, bromobenzene, caffeine, carbon tetrachloride and N-butyl-1,6-hexamediamine yielded lower LD50 values in fasted rats. The use of non-fasted rats in acute oral toxicity determinations allows both the establishment of relative potency and the estimation of dosage levels for further repeated dose oral studies. The LD50 values obtained were generally (7 of 9) higher in non-fasted rats, but the magnitude of the differences was not great enough to suggest routine use of both fasted and non-fasted rats in oral toxicity studies. PMID:6520321

  2. Interstitial pneumonitis following bone marrow transplantation after low dose rate total body irradiation

    SciTech Connect

    Barrett, A.; Depledge, M.H.; Powles, R.L.

    1983-07-01

    Idiopathic and infective interstitial pneumonitis (IPn) is a common complication after bone marrow transplantation (BMT) in many centers and carries a high mortality. We report here a series of 107 patients with acute leukemia grafted at the Royal Marsden Hospital in which only 11 (10.3%) developed IPn and only 5 died (5%). Only one case of idiopathic IPn was seen. Factors which may account for this low incidence are discussed. Sixty of 107 patients were transplanted in first remission of acute myeloid leukemia (AML) and were therefore in good general condition. Lung radiation doses were carefully monitored and doses of 10.5 Gy were not exceeded except in a group of 16 patients in whom a study of escalating doses of TBI (up to 13 Gy) was undertaken. The dose rate used for total body irradiation (TBI) was lower than that used in other centers and as demonstrated elsewhere by ourselves and others, reduction of dose rate to <0.05 Gy/min may be expected to lead to substantial reduction in lung damage. Threshold doses of approximately 8 Gy for IPn have been reported, but within the dose range of 8 to 10.5 Gy we suggest that dose rate may significantly affect the incidence. Data so far available suggest a true improvement in therapeutic ratio for low dose rate single fraction TBI compared with high dose rate.

  3. Interstitial Pneumonitis and the Risk of Chronic Allograft Rejection in Lung Transplant Recipients

    PubMed Central

    Mihalek, Andrew D.; Rosas, Ivan O.; Padera, Robert F.; Fuhlbrigge, Anne L.; Hunninghake, Gary M.; DeMeo, Dawn L.; Camp, Phillip C.

    2013-01-01

    Background: The presence of interstitial pneumonitis (IP) on surveillance lung biopsy specimens in lung transplant recipients is poorly described, and its impact on posttransplant outcomes is not established. The following study assessed the association of posttransplant IP with the development of bronchiolitis obliterans syndrome (BOS). Methods: We examined all recipients of primary cadaveric lung transplants at our institution between January 1, 2000, and December 31, 2007 (N = 145). Patients had bronchoscopies with BAL, and transbronchial biopsies performed for surveillance during posttransplant months 1, 3, 6, and 12 as well as when clinically indicated. Patients were given a diagnosis of IP if, in the absence of active infection and organizing pneumonia, they showed evidence of interstitial inflammation and fibrosis on two or more biopsy specimens. Results: IP was a significant predictor of BOS (OR, 7.84; 95% CI, 2.84-21.67; P < .0001) and was significantly associated with time to development of BOS (hazard ratio, 3.8; 95% CI, 1.93-7.39; P = .0001) within the first 6 years posttransplant. The presence of IP did not correlate with a significantly higher risk of mortality or time to death. There was no association between the presence of IP and the development of or time to acute rejection. Conclusions: The presence of IP on lung transplant biopsy specimens suggests an increased risk for BOS, which is independent of the presence of acute cellular rejection. PMID:23715594

  4. Acute toxicity of firefighting chemical formulations to four life stages of fathead minnow

    USGS Publications Warehouse

    Gaikowski, Mark P.; Hamilton, Steve J.; Buhl, Kevin J.; McDonald, Susan F.; Summers, Cliff H.

    1996-01-01

    Laboratory studies were conducted with four early life stages of fathead minnow,Pimephales promelas,to determine the acute toxicity of five firefighting chemical formulations in standardized soft and hard water. Egg, fry, 30-day posthatch, and 60-day posthatch life stages were tested with three fire retardants (Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F) and two fire-suppressant foams (Phos-Chek WD-881 and Ansul Silv-Ex). Fry were generally the most sensitive life stage tested, whereas the eggs were the least sensitive life stage. Formulation toxicity was greater in hard water than in soft water for all life stages tested. Fire-suppressant foams were more toxic than the fire retardants. The 96-hr LC50s derived for fathead minnows were rank ordered from the most toxic to the least toxic formulation as follows: Phos-Chek WD-881 (13a??32 mg/liter) > Silv-Ex (19a??32 mg/liter) > Fire-Trol GTS-R (135a??787 mg/liter) > Phos-Chek D75-F (168a??2250 mg/liter) > Fire-Trol LCG-R (519a??6705 mg/liter) (ranges are the lowest and highest 96-hr LC50for each formulation). (C) 1996 Academic Press, Inc.

  5. In vitro cytotoxicity testing of 30 reference chemicals to predict acute human and animal toxicity

    SciTech Connect

    Barile, F.A.; Arjun, S.; Borges, L. )

    1991-03-11

    This study was conducted in cooperation with the Scandinavian Society of Cell Toxicology, as part of the Multicenter Evaluation for In Vitro Cytotoxicity (MEIC), and was designed to develop an in vitro model for predicting acute human and animal toxicity. The technique relies on the ability of cultured transformed rat lung epithelial cells (L2) to incorporate radiolabled amino acids into newly synthesized proteins in the absence or presence of increasing doses of the test chemical, during a 24-hr incubation. IC50 values were extrapolated from the dose-response curves after linear regression analysis. Human toxic blood concentrations estimated from rodent LD50 values suggest that our experimental IC50's are in close correlation with the former. Validation of the data by the MEIC committee shows that our IC50 values predicted human lethal dosage as efficient as rodent LD50's. It is anticipated that this and related procedures may supplement or replace currently used animal protocols for predicting human toxicity.

  6. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 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...

  7. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 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...

  8. Gallium scanning in lymphoid interstitial pneumonitis of children with AIDS

    SciTech Connect

    Schiff, R.G.; Kabat, L.; Kamani, N.

    1987-12-01

    Lymphoid interstitial pneumonitis (LIP) is a frequent pulmonary complication in the child with the acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection. We report the gallium scan findings in two children with AIDS and LIP. Gallium scintigraphy in both children demonstrated increased radionuclide concentration throughout the lungs, a pattern indistinguishable scintigraphically from that of Pneumocystis carinii pneumonia (PCP). This should alert nuclear medicine practitioners and referring physicians to another cause of diffusely increased gallium uptake in the lungs of patients with AIDS.

  9. In silico assessment of the acute toxicity of chemicals: recent advances and new model for multitasking prediction of toxic effect.

    PubMed

    Kleandrova, Valeria V; Luan, Feng; Speck-Planche, Alejandro; Cordeiro, M Natália D S

    2015-01-01

    The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. In this sense, computational approaches involving models based on quantitative-structure activity/toxicity relationships (QSAR/QSTR) can help to rationalize time and financial costs. Here, we discuss the most significant advances in the last 6 years focused on the use of QSAR/QSTR models to predict acute toxicity of drugs/chemicals in laboratory animals, employing large and heterogeneous datasets. The advantages and drawbacks of the different QSAR/QSTR models are analyzed. As a contribution to the field, we introduce the first multitasking (mtk) QSTR model for simultaneous prediction of acute toxicity of compounds by considering different routes of administration, diverse breeds of laboratory animals, and the reliability of the experimental conditions. The mtk-QSTR model was based on artificial neural networks (ANN), allowing the classification of compounds as toxic or non-toxic. This model correctly classified more than 94% of the 1646 cases present in the whole dataset, and its applicability was demonstrated by performing predictions of different chemicals such as drugs, dietary supplements, and molecules which could serve as nanocarriers for drug delivery. The predictions given by the mtk-QSTR model are in very good agreement with the experimental results. PMID:25694074

  10. Acute lethal toxicity of some reference chemicals to freshwater fishes of Scandinavia

    SciTech Connect

    Oikari, A.O.J.

    1987-07-01

    Relevance of the choice of a test organism intended to be representative for a given environment seems to be under continual debate in aquatic ecotoxicology. For instance, it is commonly argue that acute toxicity tests with rainbow trout, the species most often recommended as a standard cold water teleost, were not representative for Nordic countries because the species is an alien in local faunas. A comparative study with several freshwater species was therefore initiated to clarify the validity of this assumption. As a first approximation, standard LC 50 assays were conducted. The species used were chosen only on the basis of their local availability, i.e, they randomly represented the fish fauna of Nordic inland waters. Furthermore, inter-species variation of toxicity response was compared with certain other, quantitatively more important, intra-species sources of variability affecting the toxicity of chemicals. Use of reference toxicants has been recommended as a means of standardizing bioassays. Compounds, characteristic of effluents from the pulp and paper industry, were selected for the present study. The toxicity of organic acids such a phenols and resin acids, as well as that of pupmill effluents, strongly depends on water pH. Because of the possibility that species differences could exist in this respect, effects of water acidity on toxicity of these types of substances to a randomly selected local species was investigated. Finally, as an example of the biological source of assay variability, the effect of yolk absorption was studied with a subsequent crisis period due to moderate starvation under laboratory conditions.

  11. Pneumonitis and pneumatoceles following accidental hydrocarbon aspiration in children.

    PubMed

    Thalhammer, Gabriela H; Eber, Ernst; Zach, Maximilian S

    2005-02-01

    Accidental ingestion and aspiration of hydrocarbons in children are common. Among the various clinical and pathological manifestations of hydrocarbon (HC) poisoning, pneumonitis is the most significant and occurs in up to 40% of children, whereas formation of pneumatoceles is believed to be a rare event. We report two children with HC pneumonitis and pneumatoceles as a reversible complication after ingestion and aspiration of lamp oil with very low viscosity. Patient 1, a 21-month-old boy, started to cough and developed tachypnea, sternal retractions and mild cyanosis immediately after aspiration. Patient 2, a 24-month-old girl, was asymptomatic during the first days after the accident; subsequently, she started to cough and developed fever, dyspnea and chest pain. Chest x-ray and computed tomography revealed multiple patchy infiltrates in both cases; after several days, these confluent infiltrates developed into pneumatoceles. Both children were treated with antibiotics and steroids. They recovered within three and four weeks, respectively, with complete remission of the radiologic abnormalities and had an uneventful follow-up after discharge. PMID:15847196

  12. Occupational hypersensitivity pneumonitis in a baker: a new cause.

    PubMed

    Gerfaud-Valentin, Mathieu; Reboux, Gabriel; Traclet, Julie; Thivolet-Béjui, Françoise; Cordier, Jean-François; Cottin, Vincent

    2014-04-01

    Bakers are exposed daily to flour and may be susceptible to immunologic occupational diseases. A 30-year-old, nonsmoking, female baker was referred for progressive dyspnea on exertion, basal crackles on auscultation, restrictive lung function, decreased diffusing capacity of the lung for carbon monoxide, ground glass hyperdensities with a mosaic pattern on high-resolution CT scan, 25% lymphocytosis by BAL, and cellular chronic bronchiolitis with peribronchiolar interstitial inflammation by lung biopsy specimen. Cultures from flours isolated nine species, including Aspergillus fumigatus. Twenty-six antigens were tested. Serum-specific precipitins were found against A fumigatus, the flour mite Acarus siro, and total extracts from maize and oat. Outcome was favorable with cessation of occupational exposure to flours and transient therapy with prednisone and immunosuppressive agents. To our knowledge, this report is the first of a well-documented case of hypersensitivity pneumonitis due to sensitization to fungi- and mite-contaminated flours. Hypersensitivity pneumonitis--and not only asthma and allergic rhinitis--should be suspected in bakers with respiratory symptoms. PMID:24687706

  13. Acute toxicity of fire-retardant and foam-suppressant chemicals to early life stages of chinook salmon (Oncorhynchus tshawytscha)

    USGS Publications Warehouse

    Buhl, K.J.; Hamilton, S.J.

    1998-01-01

    Laboratory studies were conducted to determine the acute toxicity of three fire retardants (Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75- F), and two fire-suppressant foams (Phos-Chek WD-881 and Ansul Silv-Ex) to early life stages of chinook salmon, Oncorhynchus tshawytscha, in hard and soft water. Regardless of water type, swim-up fry and juveniles (60 and 90 d posthatch) exhibited similar sensitivities to each chemical and these life stages were more sensitive than eyed eggs. Foam suppressants were more toxic to each life stage than the fire retardants in both water types. The descending rank order of toxicity for these chemicals tested with swim-up fry and juveniles (range of 96-h median lethal concentrations [LC50s]) was Phos- Chek WD-881 (7-13 mg/L) > Ansul Silv-Ex (11-22 mg/L) > Phos-Chek D75-F (218- 305 mg/L) > Fire-Trol GTS-R (218-412 mg/L) > Fire-Trol LCG-R (685-1,195 mg/L). Water type had a minor effect on the toxicity of these chemicals. Comparison of acute toxicity values with recommended application concentrations indicates that accidental inputs of these chemicals into stream environments would require substantial dilution (237- to 1,429-fold) to reach concentrations equivalent to their 96-h LC50s.

  14. Nonspecific interstitial pneumonitis: a common cause of pulmonary disease in the acquired immunodeficiency syndrome

    SciTech Connect

    Suffredini, A.F.; Ognibene, F.P.; Lack, E.E.; Simmons, J.T.; Brenner, M.; Gill, V.J.; Lane, H.C.; Fauci, A.S.; Parrillo, J.E.; Masur, H.

    1987-07-01

    During a 4.4-year period, nonspecific interstitial pneumonitis was seen in 41 of 110 (38%) patients with the acquired immunodeficiency syndrome and accounted for 32% (48/152) of all episodes of clinical pneumonitis. Diffuse alveolar damage was typically a feature of nonspecific interstitial pneumonitis, but neither lung biopsy nor bronchoalveolar lavage detected a pathogen. Of these 41 patients, 13 had no associated pulmonary tumor and had not been exposed to pulmonary toxins, whereas 28 patients had either concurrent pulmonary Kaposi sarcoma, previous experimental therapies, or a history of pneumocystis pneumonia or drug abuse. Of these 41, 23 had normal chest radiographs. The clinical features of patients with nonspecific interstitial pneumonitis were similar to those of patients with pneumocystis pneumonia, although histologic findings showed less severe alveolar damage in patients with nonspecific interstitial pneumonitis (p less than 0.001). Pathologic evaluation and clinical follow-up suggest that many clinical episodes of pneumonitis in patients with the acquired immunodeficiency syndrome are due to nonspecific interstitial pneumonitis of unknown cause.

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

    PubMed

    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. PMID:24952091

  16. Incidence and Correlates of Radiation Pneumonitis in Pediatric Patients With Partial Lung Irradiation

    SciTech Connect

    Hua Chiaho; Hoth, Kelly A.; Wu Shengjie; Kun, Larry E.; Metzger, Monika L.; Spunt, Sheri L.; Xiong Xiaoping; Krasin, Mathew J.

    2010-09-01

    Purpose: To provide a radiation pneumonitis risk estimate and investigate the correlation of clinical and dosimetric factors in pediatric patients receiving chest irradiation. Methods and Materials: A total of 122 patients diagnosed with sarcoma or Hodgkin lymphoma who received radiotherapy to the chest were evaluated for symptomatic radiation pneumonitis (Common Toxicity Criteria Grade 1 with respiratory symptom or higher grade). Pneumonitis data were collected from either prospective toxicity screenings as part of a clinical trial or through chart review. Dosimetric parameters including V{sub 10}-V{sub 25}, mean lung dose, binned lung dose, and tissue complication probability models were used, as well as clinical features to correlate with the development of pneumonitis. Results: The 1- and 2-year cumulative incidence of symptomatic radiation pneumonitis for all patients was 8.2% and 9.1%, respectively. Nine patients experienced symptomatic Grade 1 toxicity, and 2 experienced Grade 2. From univariate analysis, chemotherapy containing bleomycin ({chi}{sup 2} test, p = 0.027) and V{sub 24} (logistic regression, p = 0.019) were the clinical and dosimetric factors that resulted in statistically significant differences in the occurrence of pneumonitis. The probability of pneumonitis increased more dramatically with increasing V{sub 24} in patients receiving bleomycin than in those who did not. Adult tissue complication models did not differentiate pediatric patients with radiation pneumonitis from those without. Conclusions: The incidence of symptomatic radiation pneumonitis in pediatric patients is low and its severity mild. Parameters frequently used in adult radiation oncology provide some guidance as to risk, but pediatric patients warrant their own specific models for risk assessment, incorporating dosimetry and clinical factors.

  17. Assessing Contaminant Sensitivity of Endangered and Threatened Aquatic Species: Part I. Acute Toxicity of Five Chemicals

    EPA Science Inventory

    This paper reports on the results of acute toxicity tests conducted with common surrogate species, and several species of threatened and endangered species for which there were excess artificially propagated stock to allow direct testing.

  18. Acute environmental toxicity and persistence of DEM, a chemical agent simulant: Diethyl malonate. [Diethyl malonate

    SciTech Connect

    Cataldo, D.A.; Ligotke, M.W.; Harvey, S.D.; Fellows, R.J.; Li, Shu-mei W.; Van Voris, P.; Wentsel, R.S.

    1990-05-01

    The purpose of the following chemical simulant studies is to assess the potential acute environmental effects and persistence of diethyl malonate (DEM). Deposition velocities for DEM to soil surfaces ranged from 0.04 to 0.2 cm/sec. For foliar surfaces, deposition velocities ranged from 0.0002 cm/sec at low air concentrations to 0.05 cm/sec for high dose levels. The residence times or half-lives of DEM deposited to soils was 2 h for the fast component and 5 to 16 h for the residual material. DEM deposited to foliar surfaces also exhibited biphasic depuration. The half-life of the short residence time component ranged from 1 to 3 h, while the longer time component had half-times of 16 to 242 h. Volatilization and other depuration mechanisms reduce surface contaminant levels in both soils and foliage to less than 1% of initial dose within 96 h. DEM is not phytotoxic at foliar mass loading levels of less than 10 {mu}m/cm{sup 2}. However, severe damage is evident at mass loading levels in excess of 17 {mu}g/cm{sup 2}. Tall fescue and sagebrush were more affected than was short-needle pine, however, mass loading levels were markedly different. Regrowth of tall fescue indicated that the effects of DEM are residual, and growth rates are affected only at higher mass loadings through the second harvest. Results from in vitro testing of DEM indicated concentrations below 500 {mu}g/g dry soil generally did not negatively impact soil microbial activity. Short-term effects of DEM were more profound on soil dehydrogenase activity than on soil phosphatase activity. No enzyme inhibition or enhancement was observed after 28 days in incubation. Results of the earthworm bioassay indicate survival to be 86 and 66% at soil doses of 107 and 204 {mu}g DEM/cm{sup 2}, respectively. At higher dose level, activity or mobility was judged to be affected in over 50% of the individuals. 21 refs., 10 figs., 15 tabs.

  19. A U.S. Partnership with India and Poland to Track Acute Chemical Releases to Serve Public Health

    PubMed Central

    Ruckart, Perri Zeitz; Orr, Maureen; Pałaszewska-Tkacz, Anna; Dewan, Aruna; Kapil, Vikas

    2009-01-01

    We describe a collaborative effort between the U.S., India, and Poland to track acute chemical releases during 2005–2007. In all three countries, fixed facility events were more common than transportation-related events; manufacturing and transportation/warehousing were the most frequently involved industries; and equipment failure and human error were the primary contributing factors. The most commonly released nonpetroleum substances were ammonia (India), carbon monoxide (U.S.) and mercury (Poland). More events in India (54%) resulted in victims compared with Poland (15%) and the U.S. (9%). The pilot program showed it is possible to successfully conduct international surveillance of acute hazardous substances releases with careful interpretation of the findings. PMID:19826549

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

    SciTech Connect

    Sakamoto, Susumu Kikuchi, Naoshi; Ichikawa, Atsuo; Sano, Go; Satoh, Keita; Sugino, Keishi; Isobe, Kazutoshi; Takai, Yujiro; Shibuya, Kazutoshi; Homma, Sakae

    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.

  1. [Radiotherapy Techniques and Radiation Pneumonitis: A Lot To A Little Or A Little To A Lot?].

    PubMed

    Yu, Bingqi; Wang, Jin; Xu, Yujin; Su, Feng; Shan, Guoping; Chen, Ming

    2015-12-01

    Radiotherapy is one of the main treatment for patients with lung cancer. Three-dimensional conformal radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) are widely used to deliver radiation. Here, we focus on the correlations between dose distribution in lung and radiation pneumonitis according to the analysis about radiotherapy for lung cancer: A lot to a little or a little to a lot, which is the main cause of radiation pneumonitis? PMID:26706952

  2. Inhibition of catecholamine degradation ameliorates while chemical sympathectomy aggravates the severity of acute Friend retrovirus infection in mice.

    PubMed

    Bloemker, Dominique; Mollerus, Sina; Gibbert, Kathrin; Dittmer, Ulf; del Rey, Adriana; Schedlowski, Manfred; Engler, Harald

    2016-05-01

    Several lines of evidence indicate that the sympathetic nervous system (SNS) might be involved in the pathogenesis and progression of retroviral infections. However, experimental data are scarce and findings inconsistent. Here, we investigated the role of the SNS during acute infection with Friend virus (FV), a pathogenic murine retrovirus that causes polyclonal proliferation of erythroid precursor cells and splenomegaly in adult mice. Experimental animals were infected with FV complex, and viral load, spleen weight, and splenic noradrenaline (NA) concentration was analyzed until 25 days post infection. Results show that FV infection caused a massive but transient depletion in splenic NA during the acute phase of the disease. At the peak of the virus-induced splenomegaly, splenic NA concentration was reduced by about 90% compared to naïve uninfected mice. Concurrently, expression of the catecholamine degrading enzymes monoamine oxidase A (MAO-A) and catechol-O-methyltransferase (COMT) was significantly upregulated in immune cells of the spleen. Pharmacological inhibition of MAO-A and COMT by the selective inhibitors clorgyline and 3,5-dinitrocatechol, respectively, efficiently blocked NA degradation and significantly reduced viral load and virus-induced splenomegaly. In contrast, chemical sympathectomy prior to FV inoculation aggravated the acute infection and extended the duration of the disease. Together these findings demonstrate that catecholamine availability at the site of viral replication is an important factor affecting the course of retroviral infections. PMID:26880342

  3. Development and application of acute exposure guideline levels (AEGLs) for chemical warfare nerve and sulfur mustard agents.

    PubMed

    Watson, Annetta; Opresko, Dennis; Young, Robert; Hauschild, Veronique

    2006-01-01

    Acute exposure guideline levels (AEGLs) have been developed for the chemical warfare agents GB, GA, GD, GF, VX, and sulfur mustard. These AEGLs were approved by the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances after Federal Register publication and comment, and judged as scientifically valid by the National Research Council Committee on Toxicology Subcommittee on AEGLs. AEGLs represent general public exposure limits for durations ranging from 10 min to 8 h, and for three levels of severity (AEGL-1, AEGL-2, AEGL-3). Mild effects are possible at concentrations greater than AEGL-1, while life-threatening effects are expected at concentrations greater than AEGL-3. AEGLs can be applied to various civilian and national defense purposes, including evacuation and shelter-in-place protocols, reentry levels, protective clothing specifications, and analytical monitoring requirements. This report documents development and derivation of AEGL values for six key chemical warfare agents, and makes recommendations for their application to various potential exposure scenarios. PMID:16621779

  4. Development and Application of Acute Exposure Guideline Levels (AEGLs) for Chemical Warfare Nerve and Sulfur Mustard Agents.

    SciTech Connect

    Watson, Annetta Paule; Opresko, Dennis M; Young, Robert A; Hauschild, Veronique

    2006-01-01

    Acute exposure guideline levels (AEGLs) have been developed for the chemical warfare agents GB, GA, GD, GF, VX, and sulfur mustard. These AEGLs were approved by the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances after Federal Register publication and comment, and judged as scientifically valid by the National Research Council Committee on Toxicology Subcommittee on AEGLs. AEGLs represent general public exposure limits for durations ranging from 10 min to 8 h, and for three levels of severity (AEGL-1, AEGL-2, AEGL-3). Mild effects are possible at concentrations greater than AEGL-1, while life-threatening effects are expected at concentrations greater than AEGL-3. AEGLs can be applied to various civilian and national defense purposes, including evacuation and shelter-in-place protocols, reentry levels, protective clothing specifications, and analytical monitoring requirements. This report documents development and derivation of AEGL values for six key chemical warfare agents, and makes recommendations for their application to various potential exposure scenarios.

  5. Impact of Chemical Proportions on the Acute Neurotoxicity of a Mixture of Seven Carbamates in Rats

    EPA Science Inventory

    Environmental exposures generally involve multiple chemicals and pathways, and statistical methodologies now exist to evaluate interactions among any number of chemicals in defined mixtures. N-methyl carbamate pesticides are presumed to act through a common mode of action, that i...

  6. Acute toxicity, antiedematogenic activity, and chemical constituents of Palicourea rigida Kunth.

    PubMed

    Alves, Vanessa G; da Rosa, Elisa A; de Arruda, Laura L M; Rocha, Bruno A; Bersani Amado, Ciomar A; Santin, Silvana M O; Pomini, Armando M; da Silva, Cleuza C

    2016-03-01

    The phytochemical study of the leaves, roots, and flowers of Palicourea rigida led to the isolation of the triterpenes betulinic acid (1) and lupeol (2), the diterpene phytol (3), and the iridoid glycosides sweroside (4) and secoxyloganin (5). These compounds were identified using NMR 1H and 13C and comparing the spectra with published data. We studied the antiedematogenic activity of crude extracts from the organs, and of different fractions, in mice and found that the n-hexane fraction of the leaf extract significantly inhibited the ear edema resulting from croton oil administration. The crude extract from leaves was not acutely toxic to the mice. PMID:26927220

  7. [Aspiration pneumonitis after fire-eating: fire-eater's lung].

    PubMed

    Harding, Femke M; Hiddinga, Birgitta I; Eijsvogel, Michiel M M; van Baarlen, Joop; Oosterhof-Berktas, Richard

    2010-01-01

    On the emergency department we saw two men aged 19 and 26 with symptoms of lipoid pneumonitis (fire-eater's lung) following aspiration of petroleum during fire-eating. They were both admitted to hospital and treated with amoxicillin and clavulanic acid. Both patients were clinically recovered within a few days. Following aspiration of petroleum there is often a period of latency from 8-24 hours before the symptoms occur; it is recommended that patients should be admitted for observation. Known symptoms are coughing, shortness of breath, thoracic pain, fever, tachypnoea and sometimes haemoptysis. Apart from chest radiographs and laboratory values, taking into account the specific history, unless complications are expected additional diagnostic tests are often considered unnecessary. Treatment is symptomatic: administration of oxygen, pain relief, bronchodilation and potentially antibiotics if a bacterial superinfection is suspected. Clinical recovery is usually quick. Temporary restrictive disorders of lung function and reduced diffusion capacity have been described. Recovery of lung function and radiological recovery are seen within weeks to months. Mortality is less than 1%. PMID:21118594

  8. Occupational hypersensitivity pneumonitis in a green tea manufacturer

    PubMed Central

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

    2016-01-01

    Abstract 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 PMID:27081492

  9. Occupational hypersensitivity pneumonitis in a green tea manufacturer.

    PubMed

    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. PMID:27081492

  10. Analysis of Radiation Pneumonitis Risk Using a Generalized Lyman Model

    SciTech Connect

    Tucker, Susan L. Liu, H. Helen; Liao Zhongxing; Wei Xiong; Wang Shulian; Jin Hekun; Komaki, Ritsuko; Martel, Mary K.; Mohan, Radhe

    2008-10-01

    Purpose: To introduce a version of the Lyman normal-tissue complication probability (NTCP) model adapted to incorporate censored time-to-toxicity data and clinical risk factors and to apply the generalized model to analysis of radiation pneumonitis (RP) risk. Methods and Materials: Medical records and radiation treatment plans were reviewed retrospectively for 576 patients with non-small cell lung cancer treated with radiotherapy. The time to severe (Grade {>=}3) RP was computed, with event times censored at last follow-up for patients not experiencing this endpoint. The censored time-to-toxicity data were analyzed using the standard and generalized Lyman models with patient smoking status taken into account. Results: The generalized Lyman model with patient smoking status taken into account produced NTCP estimates up to 27 percentage points different from the model based on dose-volume factors alone. The generalized model also predicted that 8% of the expected cases of severe RP were unobserved because of censoring. The estimated volume parameter for lung was not significantly different from n = 1, corresponding to mean lung dose. Conclusions: NTCP models historically have been based solely on dose-volume effects and binary (yes/no) toxicity data. Our results demonstrate that inclusion of nondosimetric risk factors and censored time-to-event data can markedly affect outcome predictions made using NTCP models.

  11. Hypersensitivity Pneumonitis in Workers Exposed to Metalworking Fluids

    PubMed Central

    Barber, Christopher M; Burton, Clare M; Hendrick, David J; Pickering, C Anthony C; Robertson, Alastair S; Robertson, Wendy; Burge, P Sherwood

    2014-01-01

    Background This study used data from a large UK outbreak investigation, to develop and validate a new case definition for hypersensitivity pneumonitis due to metalworking fluid exposure (MWF-HP). Methods The clinical data from all workers with suspected MWF-HP were reviewed by an experienced panel of clinicians. A new MWF-HP Score was then developed to match the “gold standard” clinical opinion as closely as possible, using standard diagnostic criteria that were relatively weighted by their positive predictive value. Results The new case definition was reproducible, and agreed with expert panel opinion in 30/37 cases. This level of agreement was greater than with any of the three previously utilized case definitions (agreement in 16–24 cases). Where it was possible to calculate, the MWF-HP Score also performed well when applied to 50 unrelated MWF-HP cases. Conclusions The MWF-HP Score offers a new case definition for use in future outbreaks. Am. J. Ind. Med. 57:872–880, 2014. © 2014 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals, Inc. PMID:24954921

  12. Pneumonitis and emphysema in sp-C gene targeted mice.

    PubMed

    Glasser, Stephan W; Detmer, Emily A; Ikegami, Machiko; Na, Cheng-Lun; Stahlman, Mildred T; Whitsett, Jeffrey A

    2003-04-18

    SP-C-deficient (SP-C -/-) mice developed a severe pulmonary disorder associated with emphysema, monocytic infiltrates, epithelial cell dysplasia, and atypical accumulations of intracellular lipids in type II epithelial cells and alveolar macrophages. Whereas alveolar and tissue surfactant phospholipid pools were increased, levels of other surfactant proteins were not altered (SP-B) or were modestly increased (SP-A and SP-D). Analysis of pressure-volume curves and forced oscillatory dynamics demonstrated abnormal respiratory mechanics typical of emphysema. Lung disease was progressive, causing weight loss and cardiomegaly. Extensive alveolar remodeling was accompanied by type II cell hyperplasia, obliteration of pulmonary capillaries, and widespread expression of alpha-smooth muscle actin, indicating myofibroblast transformation in the lung parenchyma. Dysplastic epithelial cells lining conducting airways stained intensely for the mucin, MUC5A/C. Tissue concentrations of proinflammatory cytokines were not substantially altered in the SP-C (-/-) mice. Production of matrix metalloproteinases (MMP-2 and MMP-9) was increased in alveolar macrophages from SP-C (-/-) mice. Absence of SP-C caused a severe progressive pulmonary disorder with histologic features consistent with interstitial pneumonitis. PMID:12519727

  13. Development of short, acute exposure hazard estimates: a tool for assessing the effects of chemical spills in aquatic environments.

    PubMed

    Bejarano, Adriana C; Farr, James K

    2013-08-01

    Management decisions aimed at protecting aquatic resources following accidental chemical spills into rivers and coastal estuaries require estimates of toxic thresholds derived from realistic spill conditions: acute pulse exposures of short duration (h), information which often is unavailable. Most existing toxicity data (median lethal concentration or median effective concentration) come from tests performed under constant exposure concentrations and exposure durations in the 24-h to 96-h range, conditions not typical of most chemical spills. Short-exposure hazard concentration estimates were derived for selected chemicals using empirical toxicity data. Chemical-specific 5th percentile hazard concentrations (HC5) of species sensitivity distributions (SSD) from individual exposure durations (6-96 h) were derived via bootstrap resampling and were plotted against their original exposure durations to estimate HC5s and 95% confidence intervals (CIs) at shorter exposures (1, 2, and 4 h). This approach allowed the development of short-exposure HC5s for 12 chemicals. Model verification showed agreement between observed and estimated short-exposure HC5s (r(2) adjusted = 0.95, p < 0.0001), and comparison of estimated short-exposure HC5s with empirical toxicity data indicated generally conservative hazard estimates. This approach, applied to 2 real spill incidents, indicated hazard estimates above expected environmental concentrations (acrylonitrile), and suggested that environmental concentrations likely exceeded short-exposure hazard estimates (furfural). Although estimates generated through this approach were likely overprotective, these were derived from environmentally realistic exposure durations, providing risk-assessors with a tool to manage field decisions. Environ Toxicol Chem 2013;32:1918-1927. © 2013 SETAC. PMID:23625642

  14. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury

    PubMed Central

    Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F.; Liu, Boyi; Kaelberer, Melanie M.; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S.; Ye, Guosen; Willette, Robert N.; Thorneloe, Kevin S.; Bradshaw, Heather B.; Matalon, Sadis

    2014-01-01

    The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. PMID:24838754

  15. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury.

    PubMed

    Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F; Liu, Boyi; Kaelberer, Melanie M; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S; Ye, Guosen; Willette, Robert N; Thorneloe, Kevin S; Bradshaw, Heather B; Matalon, Sadis; Jordt, Sven-Eric

    2014-07-15

    The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. PMID:24838754

  16. Acute toxicity of current and alternative oil spill chemical dispersants to early life stage blue crabs (Callinectes sapidus).

    PubMed

    Pie, Hannah V; Mitchelmore, Carys L

    2015-06-01

    The aim of this study was to examine the acute toxicity of five oil spill chemical dispersants on the ecologically and economically important coastal and estuarine species, blue crab Callinectes sapidus. Static, non-renewal 48 h acute toxicity tests were performed on stage-II blue crab zoea. The median lethal concentration (LC50) was calculated for each dispersant at 24 h and 48 h using nominal concentrations for each dispersant tested. The 48 h LC50 values from the most to the least toxic ranged from 10.1 mg L(-1) for Dispersit SPC 1000 to 76.5 mg L(-1) for Orca. For all dispersants, the swimming activity and mobility of larvae decreased with increasing dispersant concentration within 24h of exposure and reached relative immobility at concentrations below LC50 values. These results show that the dispersants examined in this study are only slightly toxic after 48 h exposure to the earliest life stage of blue crabs that might likely be exposed to dispersants in the environment, with the exception of Dispersit SPC 1000 that bordered between slightly and moderately toxic. Although the dispersants themselves appear to not cause substantial acute toxicity, sublethal and potentially delayed impacts, such as, reduced mobility or food source availability could indirectly remove larvae from the population and need to be further examined, as do larval responses in standard chronic toxicity tests. Furthermore, dispersants are not released into the environment in isolation and so the impact of dispersed-oil using these dispersant formulations also needs to be investigated to translate into real-world situations. PMID:25637788

  17. Predicting Radiation Pneumonitis After Chemoradiation Therapy for Lung Cancer: An International Individual Patient Data Meta-analysis

    SciTech Connect

    Palma, David A.; Senan, Suresh; Tsujino, Kayoko; Barriger, Robert B.; Rengan, Ramesh; Moreno, Marta; Bradley, Jeffrey D.; Kim, Tae Hyun; Ramella, Sara; Marks, Lawrence B.; De Petris, Luigi; Stitt, Larry; Rodrigues, George

    2013-02-01

    Background: Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis. Methods and Materials: After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade {>=}2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups. Results: The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving {>=}20 Gy (V{sub 20}) (odds ratio [OR] 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P<.001), with a trend for age (OR 1.24 per decade, P=.09); the model remained predictive in the validation set with good discrimination in both datasets (c-statistic >0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V{sub 20}, and lower-lobe tumor location. Conclusions: Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location.

  18. Assessing chronic fish health: An application to a case of an acute exposure to chemically treated crude oil.

    PubMed

    Mauduit, F; Domenici, P; Farrell, A P; Lacroix, C; Le Floch, S; Lemaire, P; Nicolas-Kopec, A; Whittington, M; Zambonino-Infante, J L; Claireaux, G

    2016-09-01

    Human alteration of marine ecosystems is substantial and growing. Yet, no adequate methodology exists that provides reliable predictions of how environmental degradation will affect these ecosystems at a relevant level of biological organization. The primary objective of this study was to develop a methodology to evaluate a fish's capacity to face a well-established environmental challenge, an exposure to chemically dispersed oil, and characterize the long-term consequences. Therefore, we applied high-throughput, non-lethal challenge tests to assess hypoxia tolerance, temperature susceptibility and maximal swimming speed as proxies for a fish's functional integrity. These whole animal challenge tests were implemented before (1 month) and after (1 month) juvenile European sea bass (Dicentrarchus labrax) had been acutely exposed (48h) to a mixture containing 0.08gL(-1) of weathered Arabian light crude oil plus 4% dispersant (Corexit© EC9500A), a realistic exposure concentration during an oil spill. In addition, experimental populations were then transferred into semi-natural tidal mesocosm ponds and correlates of Darwinian fitness (growth and survival) were monitored over a period of 4 months. Our results revealed that fish acutely exposed to chemically dispersed oil remained impaired in terms of their hypoxia tolerance and swimming performance, but not in temperature susceptibility for 1 month post-exposure. Nevertheless, these functional impairments had no subsequent ecological consequences under mildly selective environmental conditions since growth and survival were not impacted during the mesocosm pond study. Furthermore, the earlier effects on fish performance were presumably temporary because re-testing the fish 10 months post-exposure revealed no significant residual effects on hypoxia tolerance, temperature susceptibility and maximal swimming speed. We propose that the functional proxies and correlates of Darwinian fitness used here provide a useful

  19. Patterns of clinical bioindicators in rat serum following acute exposure to pesticides of different chemical classes

    EPA Science Inventory

    There is interest in bioindicators of adverse outcomes in safety assessment and translational research. Chemically-induced neurological effects may be reflected in specific neuronal changes and/or by general stress-like responses, and such bioindicators may be useful for measurin...

  20. Acute and Long-Term Impact of Chemical Weapons: Lessons from the Iran-Iraq War.

    PubMed

    Haines, D D; Fox, S C

    2014-07-01

    Chemical weapons have given the human experience of warfare a uniquely terrifying quality that has inspired a general repugnance and led to periodic attempts to ban their use. Nevertheless, since ancient times, toxic agents have been consistently employed to kill and terrorize target populations. The evolution of these weapons is examined here in ways that may allow military, law enforcement, and scientific professionals to gain a perspective on conditions that, in the past, have motivated their use - both criminally and as a matter of national policy during military campaigns. Special emphasis is placed on the genocidal use of chemical weapons by the regime of Saddam Hussein, both against Iranians and on Kurdish citizens of his own country, during the Iran-Iraq War of 1980-88. The historical development of chemical weapons use is summarized to show how progressively better insight into biochemistry and physiology was adapted to this form of warfare. Major attributes of the most frequently used chemical agents and a description of how they affected military campaigns are explained. Portions of this review describing chemical-casualty care devote particular focus to Iranian management of neurotoxic (nerve) agent casualties due to the unique nature of this experience. Both nerve and blistering "mustard" agents were used extensively against Iranian forces. However, Iran is the only nation in history to have sustained large-scale attacks with neurotoxic weapons. For this reason, an understanding of the successes and failures of countermeasures to nerve-agent use developed by the Iranian military are particularly valuable for future civil defense and military planning. A detailed consideration of these strategies is therefore considered. Finally, the outcomes of clinical research into severe chronic disease triggered by mustard-agent exposure are examined in the context of the potential of these outcomes to determine the etiology of illness among US and Allied veterans

  1. Viral Pneumonitis Is Increased in Obese Patients during the First Wave of Pandemic A(H1N1) 2009 Virus

    PubMed Central

    Kok, Jen; Blyth, Christopher C.; Foo, Hong; Bailey, Michael J.; Pilcher, David V.; Webb, Steven A.; Seppelt, Ian M.; Dwyer, Dominic E.; Iredell, Jonathan R.

    2013-01-01

    Introduction There is conflicting data as to whether obesity is an independent risk factor for mortality in severe pandemic (H1N1) 2009 influenza (A(H1N1)pdm09). It is postulated that excess inflammation and cytokine production in obese patients following severe influenza infection leads to viral pneumonitis and/or acute respiratory distress syndrome. Methods Demographic, laboratory and clinical data prospectively collected from obese and non-obese patients admitted to nine adult Australian intensive care units (ICU) during the first A(H1N1)pdm09 wave, supplemented with retrospectively collected data, were compared. Results Of 173 patients, 100 (57.8%), 73 (42.2%) and 23 (13.3%) had body mass index (BMI) <30 kg/m2, ≥30 kg/m2 (obese) and ≥40 kg/m2 (morbidly obese) respectively. Compared to non-obese patients, obese patients were younger (mean age 43.4 vs. 48.4 years, p = 0.035) and more likely to develop pneumonitis (61% vs. 44%, p = 0.029). Extracorporeal membrane oxygenation use was greater in morbidly obese compared to non-obese patients (17.4% vs. 4.7%, p = 0.04). Higher mortality rates were observed in non-obese compared to obese patients, but not after adjusting for severity of disease. C-reactive protein (CRP) levels and hospital length of stay (LOS) were similar. Amongst ICU survivors, obese patients had longer ICU LOS (median 11.9 vs. 6.8 days, p = 0.017). Similar trends were observed when only patients infected with A(H1N1)pdm09 were examined. Conclusions Among patients admitted to ICU during the first wave of A(H1N1)pdm09, obese and morbidly obese patients with severe infection were more likely to develop pneumonitis compared to non-obese patients, but mortality rates were not increased. CRP is not an accurate marker of pneumonitis. PMID:23418448

  2. Docetaxel-induced hypersensitivity pneumonitis mimicking lymphangitic carcinomatosis in a patient with metastatic adenocarcinoma of the lung.

    PubMed

    Taj, Asma

    2013-01-01

    Docetaxel belongs to the taxane family of anti-cancer drugs, which are commonly used in non-small cell lung cancers. They stabilize microtubules by preventing depolymerization, resulting in cell death. Pneumonitis is an uncommon side effect of docetaxel. We report a case of docetaxel induced hypersensitivity pneumonitis mimicking lymphangitic carcinomatosis in a patient with metastatic adenocarcinoma of the lung. PMID:24096092

  3. Lymphangiogenic factors are associated with the severity of hypersensitivity pneumonitis

    PubMed Central

    Yamashita, Masahiro; Mouri, Takashi; Niisato, Miyuki; Nitanai, Hiroo; Kobayashi, Hitoshi; Ogasawara, Masahito; Endo, Ryujin; Konishi, Kazuki; Sugai, Tamotsu; Sawai, Takashi; Yamauchi, Kohei

    2015-01-01

    Background Antigen presenting cells play a pivotal role in the adaptive immune response in hypersensitivity pneumonitis (HP). It was hypothesised that lymphangiogenesis is involved in the pathophysiology of HP via cell transport. Objective To determine the clinical significance of lymphangiogenic factors in HP. Methods Levels of vascular endothelial growth factors (VEGF)-A, VEGF-C, VEGF-D and CCL21 in the serum and bronchoalveolar lavage fluid (BALF) were measured in 29 healthy volunteers, 14 patients with idiopathic pulmonary fibrosis (IPF) and 26 patients with HP by ELISA. Additionally, immunohistochemical analyses were performed using lung specimens of patients with HP (n=8) and IPF (n=10). Results BALF VEGF-D levels were significantly elevated in patients with HP compared to the other groups. BALF VEGF–D levels in patients with HP correlated significantly with the BALF total cell and lymphocyte counts (r=0.485, p=0.014 and r=0.717, p<0.0001, respectively). BALF VEGF-C and CCL21 levels were increased in patients with HP compared to healthy volunteers, but not patients with IPF. BALF CCL21 levels were negatively correlated with the forced expiratory volume in 1 s percentage and diffuse capacity of the lung for carbon monoxide (r=−0.662, p=0.007 and r=−0.671, p=0.024, respectively). According to the immunohistochemical analyses, CCL21 was expressed in the lymphatic endothelium in both conditions and CCR7+ cells were aggregated around lymphatics in patients with HP, but not in patients with IPF. Conclusions Lymphangiogenic factors might be associated with the inflammatory and functional severity of HP. The increased BALF VEGF-D levels were associated with lymphatic alveolitis intensity, and CCL21 with lung function impairment. PMID:26448865

  4. Blast cells transfer experimental hypersensitivity pneumonitis in guinea pigs

    SciTech Connect

    Schuyler, M.; Cook, C.; Listrom, M.; Fengolio-Preiser, C.

    1988-06-01

    We previously demonstrated that experimental hypersensitivity pneumonitis (HP) can be transferred by lymph node cells (LNC) cultured in vitro with antigen. The purpose of this study was to identify the cells responsible for transfer and to determine if pulmonary cells can transfer HP. We cultured LNC from sensitized Strain 2 guinea pigs with a soluble extract of Micropolyspora faeni for 72 h, separated lymphoblasts from small lymphocytes, and transferred both subpopulations intravenously to syngeneic recipients. We also transferred irradiated lymphoblasts (1,500 rads), macrophage-depleted, lymphoblast-enriched populations, and pulmonary cells either without culture or after culture with M. faeni. Control animals received an equal volume of medium. All recipient animals were challenged intratracheally (i.t.) with M. faeni 48 h after the cell transfer, and they were killed 4 days after i.t. challenge. Randomly selected microscopic fields of the lung (250/animal) were judged to be normal or abnormal without knowledge of treatment. This measurement was reproducible (r = 0.95 for duplicate measurements, n = 55). All guinea pigs were maintained in HEPA-filtered air. There was a low level of pulmonary response to an i.t. challenge of M. faeni in animals that received medium. Animals that received pulmonary cells, either cultured or noncultured, did not differ from those in the control group. There was a substantial increase (p less than 0.01) in the extent of pulmonary abnormalities in the recipients of the lymphoblast population, with significant correlation (r = 0.87, p less than 0.01) between the number of lymphoblasts transferred and the extent of pulmonary abnormalities.

  5. Acute toxicity of Daphnia pulex to six classes of chemical compounds potentially hazardous to Great Lakes aquatic biota

    USGS Publications Warehouse

    Smith, Stephen B.; Savino, Jacqueline F.; Blouin, Marc A.

    1988-01-01

    Of the six classes of chemicals potentially hazardous to Great Lakes aquatic biota, derivatives of polyaromatic hydrocarbons (PAHs) were the most acutely toxic (48-h EC 50) to Daphnia pulex. The other classes, listed in order of decreasing toxicity were alkyl halides, nitrogen-containing compounds, cyclic alkanes, heterocyclic nitrogen compounds, silicon-containing compounds. O f the 41 compounds representing the six chemical classes, 6 were extremely toxic (> 0.01 - 0.1 mg/L), 11 highly toxic (> 01. - 1.0 mg/L), 20 moderately toxic (> 1.0 - 10.0 mg/L), and 4 slightly toxic (>10 - 100 mg/L). The reference compound, p, p'DDT, was super toxic (< 0.01 mg/L). Based on toxicity and relative abundance (hazard ranking) of the 21 compounds that were detected in tissue of Great Lakes fishes, the classes of compounds that present the greatest threat to Great Lakes aquatic biota are PAH derivatives, alkyl halides, and cyclic aklanes.

  6. USE OF THE FUNGICIDE CARBENDAZIM AS A MODEL COMPOUND TO DETERMINE THE IMPACT OF ACUTE CHEMICAL EXPOSURE DURING OOCYTE MATURATION AND FERTILIZATION ON PREGNANCY OUTCOME IN THE HAMSTER

    EPA Science Inventory

    Here we use a hamster animal model to identify early pregnancy loss due to an acute chemical exposure to the female during the perifertilization interval. The fungicide carbendazim (methyl 1H-benzimidazole-2-carbamate), a microtubule poison with antimitotic activity, was selected...

  7. Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy

    SciTech Connect

    Lingos, T.I.; Recht, A.; Vicini, F.; Abner, A.; Silver, B.; Harris, J.R. )

    1991-07-01

    The likelihood of radiation pneumonitis and factors associated with its development in breast cancer patients treated with conservative surgery and radiation therapy have not been well established. To assess these, the authors retrospectively reviewed 1624 patients treated between 1968 and 1985. Median follow-up for patients without local or distant failure was 77 months. Patients were treated with either tangential fields alone (n = 508) or tangents with a third field to the supraclavicular (SC) or SC-axillary (AX) region (n = 1116). Lung volume treated in the tangential fields was generally limited by keeping the perpendicular distance (demagnified) at the isocenter from the deep field edges to the posterior chest wall (CLD) to 3 cm or less. Seventeen patients with radiation pneumonitis were identified (1.0%). Radiation pneumonitis was diagnosed when patients presented with cough (15/17, 88%), fever (9/17, 53%), and/or dyspnea (6/17, 35%) and radiographic changes (17/17) following completion of RT. Radiographic infiltrates corresponded to treatment portals in all patients, and in 12 of the 17 patients, returned to baseline within 1-12 months. Five patients had permanent scarring on chest X ray. No patient had late or persistent pulmonary symptoms. The incidence of radiation pneumonitis was correlated with the combined use of chemotherapy (CT) and a third field. Three percent (11/328) of patients treated with a 3-field technique who received chemotherapy developed radiation pneumonitis compared to 0.5% (6 of 1296) for all other patients (p = 0.0001). When patients treated with a 3-field technique received chemotherapy concurrently with radiation therapy, the incidence of radiation pneumonitis was 8.8% (8/92) compared with 1.3% (3/236) for those who received sequential chemotherapy and radiation therapy (p = 0.002).

  8. Profiling of the Tox21 Chemical Collection for Mitochondrial Function to Identify Compounds that Acutely Decrease Mitochondrial Membrane Potential

    PubMed Central

    Attene-Ramos, Matias S.; Huang, Ruili; Michael, Sam; Witt, Kristine L.; Richard, Ann; Tice, Raymond R.; Simeonov, Anton; Austin, Christopher P.

    2014-01-01

    21 chemical collection for mitochondrial function to identify compounds that acutely decrease mitochondrial membrane potential. Environ Health Perspect 123:49–56; http://dx.doi.org/10.1289/ehp.1408642 PMID:25302578

  9. Predicting Pneumonitis Risk: A Dosimetric Alternative to Mean Lung Dose

    SciTech Connect

    Tucker, Susan L.; Mohan, Radhe; Liengsawangwong, Raweewan; Martel, Mary K.; Liao Zhongxing

    2013-02-01

    Purpose: To determine whether the association between mean lung dose (MLD) and risk of severe (grade {>=}3) radiation pneumonitis (RP) depends on the dose distribution pattern to normal lung among patients receiving 3-dimensional conformal radiation therapy for non-small-cell lung cancer. Methods and Materials: Three cohorts treated with different beam arrangements were identified. One cohort (2-field boost [2FB]) received 2 parallel-opposed (anteroposterior-posteroanterior) fields per fraction initially, followed by a sequential boost delivered using 2 oblique beams. The other 2 cohorts received 3 or 4 straight fields (3FS and 4FS, respectively), ie, all fields were irradiated every day. The incidence of severe RP was plotted against MLD in each cohort, and data were analyzed using the Lyman-Kutcher-Burman (LKB) model. Results: The incidence of grade {>=}3 RP rose more steeply as a function of MLD in the 2FB cohort (N=120) than in the 4FS cohort (N=138), with an intermediate slope for the 3FS group (N=99). The estimated volume parameter from the LKB model was n=0.41 (95% confidence interval, 0.15-1.0) and led to a significant improvement in fit (P=.05) compared to a fit with volume parameter fixed at n=1 (the MLD model). Unlike the MLD model, the LKB model with n=0.41 provided a consistent description of the risk of severe RP in all three cohorts (2FB, 3FS, 4FS) simultaneously. Conclusions: When predicting risk of grade {>=}3 RP, the mean lung dose does not adequately take into account the effects of high doses. Instead, the effective dose, computed from the LKB model using volume parameter n=0.41, may provide a better dosimetric parameter for predicting RP risk. If confirmed, these findings support the conclusion that for the same MLD, high doses to small lung volumes ('a lot to a little') are worse than low doses to large volumes ('a little to a lot').

  10. QSAR models for predicting the acute toxicity of selected organic chemicals with diverse structures to aquatic non-vertebrates and humans.

    PubMed

    Calleja, M C; Geladi, P; Persoone, G

    1994-01-01

    The linear and non-linear relationships of acute toxicity (as determined on five aquatic non-vertebrates and humans) to molecular structure have been investigated on 38 structurally-diverse chemicals. The compounds selected are the organic chemicals from the 50 priority chemicals prescribed by the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) programme. The models used for the evaluations are the best combination of physico-chemical properties that could be obtained so far for each organism, using the partial least squares projection to latent structures (PLS) regression method and backpropagated neural networks (BPN). Non-linear models, whether derived from PLS regression or backpropagated neural networks, appear to be better than linear models for describing the relationship between acute toxicity and molecular structure. BPN models, in turn, outperform non-linear models obtained from PLS regression. The predictive power of BPN models for the crustacean test species are better than the model for humans (based on human lethal concentration). The physico-chemical properties found to be important to predict both human acute toxicity and the toxicity to aquatic non-vertebrates are the n-octanol water partition coefficient (Pow) and heat of formation (HF). Aside from the two former properties, the contribution of parameters that reflect size and electronic properties of the molecule to the model is also high, but the type of physico-chemical properties differs from one model to another. In all of the best BPN models, some of the principal component analysis (PCA) scores of the 13C-NMR spectrum, with electron withdrawing/accepting capacity (LUMO, HOMO and IP) are molecular size/volume (VDW or MS1) parameters are relevant. The chemical deviating from the QSAR models include non-pesticides as well as some of the pesticides tested. The latter type of chemical fits in a number of the QSAR models. Outliers for one species may be different from those of other test

  11. A microfluidic device to study neuronal and motor responses to acute chemical stimuli in zebrafish

    PubMed Central

    Candelier, Raphaël; Sriti Murmu, Meena; Alejo Romano, Sebastián; Jouary, Adrien; Debrégeas, Georges; Sumbre, Germán

    2015-01-01

    Zebrafish larva is a unique model for whole-brain functional imaging and to study sensory-motor integration in the vertebrate brain. To take full advantage of this system, one needs to design sensory environments that can mimic the complex spatiotemporal stimulus patterns experienced by the animal in natural conditions. We report on a novel open-ended microfluidic device that delivers pulses of chemical stimuli to agarose-restrained larvae with near-millisecond switching rate and unprecedented spatial and concentration accuracy and reproducibility. In combination with two-photon calcium imaging and recordings of tail movements, we found that stimuli of opposite hedonic values induced different circuit activity patterns. Moreover, by precisely controlling the duration of the stimulus (50–500 ms), we found that the probability of generating a gustatory-induced behavior is encoded by the number of neurons activated. This device may open new ways to dissect the neural-circuit principles underlying chemosensory perception. PMID:26194888

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

    SciTech Connect

    Gross, N.J.; Holloway, N.O.; Narine, K.R. )

    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.

  13. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. 113.71 Section 113.71 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS...

  14. Hypersensitivity Pneumonitis by a Cool-Mist Vaporizer a Detailed Microbiologic and Immunologic Study

    PubMed Central

    Chung, Jae Chun; Choi, Jin Myung; Lee, Hyun Woo; Hong, Suhk; Kim, Chung Sook

    1989-01-01

    A patient with hypersensitivity pneumonitis caused by a contaminated cool-mist vaporizer was evaluated. A detailed microbiologic and immunologic study was done, and a Pseudomonas species was isolated as the possible causative organism by inhalational provocative and serologic tests. PMID:2486849

  15. Antinociceptive effects, acute toxicity and chemical composition of Vitex agnus-castus essential oil

    PubMed Central

    Khalilzadeh, Emad; Vafaei Saiah, Gholamreza; Hasannejad, Hamideh; Ghaderi, Adel; Ghaderi, Shahla; Hamidian, Gholamreza; Mahmoudi, Razzagh; Eshgi, Davoud; Zangisheh, Mahsa

    2015-01-01

    Objective: Vitex agnus-castus (VAC) and its essential oil have been traditionally used to treat many conditions and symptoms such as premenstrual problems, mastalgia, inflammation, sexual dysfunction, and pain. In this study, the effects of essential oil extracted from Vitex agnus-castus (EOVAC) leaves were investigated in three behavioral models of nociception in adult male Wistar rats. Materials and methods: Chemical composition of EOVAC was analyzed using gas chromatography – mass spectrometry (GC-MS) and also its possible toxicity was determined in mice. Analgesic effect of EOVAC was determined using tail immersion test, formalin test, and acetic acid-induced visceral pain in rats. Results: EOVAC (s.c.) and morphine (i.p.) significantly (p<0.05) reduced pain responses in both formalin and tail immersion tests. In the study of evolved mechanisms, pretreatment with naloxone or atropine significantly (p <0.05) reversed the essential oil-induced analgesia in both formalin and tail immersion tests. Moreover, EOVAC and Piroxicam produced significant (p<0.05) inhibition in the acetic acid-induced writhing response. EOVAC did not show any mortality even at high dose (5 g/kg, p.o.) of administration in toxicity test. Moreover, according to GC-MS results, major components of the EOVAC were α-pinene (14.83%), limonene (10.29%), β-caryophyllene (6.9%), sabinene (5.27%), and β-farnesene (5.9%). Conclusions: These results suggest that endogenous opioidergic system as well as muscarinergic receptors of cholinergic system may be involve in the antinociceptive activity of Vitex agnus-castus essential oil in these models of pain in rats. PMID:26101755

  16. Limitations and challenges in treatment of acute chemical warfare agent poisoning.

    PubMed

    Thiermann, Horst; Worek, Franz; Kehe, Kai

    2013-12-01

    Recent news from Syria on a possible use of chemical warfare agents made the headlines. Furthermore, the motivation of terrorists to cause maximal harm shifts these agents into the public focus. For incidents with mass casualties appropriate medical countermeasures must be available. At present, the most important threats arise from nerve agents and sulfur mustard. At first, self-protection and protection of medical units from contamination is of utmost importance. Volatile nerve agent exposure, e.g. sarin, results in fast development of cholinergic crisis. Immediate clinical diagnosis can be confirmed on-site by assessment of acetylcholinesterase activity. Treatment with autoinjectors that are filled with 2mg atropine and an oxime (at present obidoxime, pralidoxime, TMB-4 or HI-6) are not effective against all nerve agents. A more aggressive atropinisation has to be considered and more effective oximes (if possible with a broad spectrum or a combination of different oximes) as well as alternative strategies to cope with high acetylcholine levels at synaptic sites should be developed. A further gap exists for the treatment of patients with sustained cholinergic crisis that has to be expected after exposure to persistent nerve agents, e.g. VX. The requirement for long-lasting artificial ventilation can be reduced with an oxime therapy that is optimized by using the cholinesterase status for guidance or by measures (e.g. scavengers) that are able to reduce the poison load substantially in the patients. For sulfur mustard poisoning no specific antidote is available until now. Symptomatic measures as used for treatment of burns are recommended together with surgical or laser debridement. Thus, huge amounts of resources are expected to be consumed as wound healing is impaired. Possible depots of sulfur mustard in tissues may aggravate the situation. More basic knowledge is necessary to improve substantially therapeutic options. The use of stem cells may provide a new

  17. Radiation pneumonitis and pulmonary fibrosis in non-small-cell lung cancer: Pulmonary function, prediction, and prevention

    SciTech Connect

    Mehta, Vivek . E-mail: Vivek.Mehta@swedish.org

    2005-09-01

    Although radiotherapy improves locoregional control and survival in patients with non-small-cell lung cancer, radiation pneumonitis is a common treatment-related toxicity. Many pulmonary function tests are not significantly altered by pulmonary toxicity of irradiation, but reductions in DL{sub CO}, the diffusing capacity of carbon monoxide, are more commonly associated with pneumonitis. Several patient-specific factors (e.g. age, smoking history, tumor location, performance score, gender) and treatment-specific factors (e.g. chemotherapy regimen and dose) have been proposed as potential predictors of the risk of radiation pneumonitis, but these have not been consistently demonstrated across different studies. The risk of radiation pneumonitis also seems to increase as the cumulative dose of radiation to normal lung tissue increases, as measured by dose-volume histograms. However, controversy persists about which dosimetric parameter optimally predicts the risk of radiation pneumonitis, and whether the volume of lung or the dose of radiation is more important. Radiation oncologists ought to consider these dosimetric factors when designing radiation treatment plans for all patients who receive thoracic radiotherapy. Newer radiotherapy techniques and technologies may reduce the exposure of normal lung to irradiation. Several medications have also been evaluated for their ability to reduce radiation pneumonitis in animals and humans, including corticosteroids, amifostine, ACE inhibitors or angiotensin II type 1 receptor blockers, pentoxifylline, melatonin, carvedilol, and manganese superoxide dismutase-plasmid/liposome. Additional research is warranted to determine the efficacy of these medications and identify nonpharmacologic strategies to predict and prevent radiation pneumonitis.

  18. Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and interlaboratory testing, life stage, and species.

    PubMed

    Raimondo, Sandy; Lilavois, Crystal R; Lee, Larisa; Augspurger, Tom; Wang, Ning; Ingersoll, Chris G; Bauer, Candice; Hammer, Edward; Barron, Mace G

    2016-03-01

    The authors developed a toxicity database for unionid mussels to examine the extent of intra- and interlaboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the 2 life stages; and the variation in sensitivity among commonly tested mussels (Lampsilis siliquoidea, Utterbackia imbecillis, and Villosa iris), commonly tested cladocerans (Daphnia magna and Ceriodaphnia dubia), and fish (Oncorhynchus mykiss, Pimephales promelas, and Lepomis macrochirus). The results of these analyses indicate that intralaboratory variability for median effect concentrations (EC50) averaged about 2-fold for both life stages, whereas interlaboratory variability averaged 3.6-fold for juvenile mussels and 6.3-fold for glochidia. The EC50s for juveniles and glochidia were within a factor of 2 of each other for 50% of paired records across chemicals, with juveniles more sensitive than glochidia by more than 2-fold for 33% of the comparisons made between life stages. There was a high concurrence of sensitivity of commonly tested L. siliquoidea, U. imbecillis, and V. iris to that of other mussels. However, this concurrence decreased as the taxonomic distance of the commonly tested cladocerans and fish to mussels increased. The compiled mussel database and determination of data variability will advance risk assessments by including more robust species sensitivity distributions, interspecies correlation estimates, and availability of taxon-specific empirically derived application factors for risk assessment. PMID:26369904

  19. Case report of two patients having successful surgery for lung cancer after treatment for Grade 2 radiation pneumonitis

    PubMed Central

    Nakajima, Yuki; Akiyama, Hirohiko; Kinoshita, Hiroyasu; Atari, Maiko; Fukuhara, Mitsuro; Saito, Yoshihiro; Sakai, Hiroshi; Uramoto, Hidetaka

    2015-01-01

    Introduction Surgery for locally advanced lung cancer is carried out following chemoradiotherapy. However, there are no reports clarifying what the effects on the subsequent prognosis are when surgery is carried out in cases with radiation pneumonitis. In this paper, we report on 2 cases of non-small cell lung cancer with Grade 2 radiation pneumonitis after induction chemoradiotherapy, in which we were able to safely perform radical surgery subsequent to the treatment for pneumonia. Presentation of cases Case 1 was a 68-year-old male with a diagnosis of squamous cell lung cancer cT2aN2M0, Stage IIIA. Sixty days after completion of the radiotherapy, Grade 2 radiation pneumonitis was diagnosed. After administration of predonine, and upon checking that the radiation pneumonitis had improved, radical surgery was performed. Case 2 was a 63-year-old male. He was diagnosed with squamous cell lung cancer cT2bN1M0, Stage IIB. One hundred and twenty days after completion of the radiotherapy, he was diagnosed with Grade 2 radiation pneumonitis. After administration of predonine, the symptoms disappeared, and radical surgery was performed. In both cases, the postoperative course was favorable, without complications, and the patients were discharged. Conclusion Surgery for lung cancer on patients with Grade 2 radiation pneumonitis should be deferred until the patients complete steroid therapy, and the clinical pneumonitis is cured. Moreover, it is believed that it is important to remove the resolved radiation pneumonitis without leaving any residual areas and not to cut into any areas of active radiation pneumonitis as much as possible. PMID:26793310

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

    PubMed

    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. PMID:23195858

  1. Chemical comparison and acute toxicity of water accommodated fraction (WAF) of source and field collected Macondo oils from the Deepwater Horizon spill.

    PubMed

    Faksness, Liv-Guri; Altin, Dag; Nordtug, Trond; Daling, Per S; Hansen, Bjørn Henrik

    2015-02-15

    Two Source oils and five field collected oil residues from the Deepwater Horizon incident were chemically characterized. Water accommodated fractions (WAFs) of the Source oils and two of the field-weathered oils were prepared to evaluate the impact of natural weathering on the chemical composition and the acute toxicity of the WAFs. Toxicity test species representing different tropic levels were used (the primary producer Skeletonema costatum (algae) and the herbivorous copepod Acartia tonsa). The results suggest that the potential for acute toxicity is higher in WAFs from non-weathered oils than WAFs from the field weathered oils. The Source oils contained a large fraction of soluble and bioavailable components (such as BTEX (benzene, toluene, ethyl benzene, xylenes) and naphthalene), whereas in the surface collected oils these components were depleted by dissolution into the water column as the oil rose to the surface and by evaporative loss after reaching the sea surface. PMID:25534626

  2. Acute toxicity of chemically and mechanically dispersed crude oil to juvenile sea bass (Dicentrarchus labrax): Absence of synergistic effects between oil and dispersants.

    PubMed

    Dussauze, Matthieu; Pichavant-Rafini, Karine; Le Floch, Stéphane; Lemaire, Philippe; Theron, Michaël

    2015-07-01

    The goal of the present experiment was to assess the relative acute toxicities of mechanically and chemically dispersed oil (crude Arabian Light) in controlled conditions. Juvenile sea bass (Dicentrarchus labrax) were exposed to 4 commercial formulations of dispersants (Corexit EC9500A, Dasic Slickgone NS, Finasol OSR 52, Inipol IP 90), to mechanically dispersed oil, and to the corresponding chemical dispersions. Acute toxicity was evaluated at 24 h, 48 h, 72 h, and 96 h through the determination of 10%, 50%, and 90% lethal concentrations calculated from measured total petroleum hydrocarbon (TPH) concentrations; Kaplan-Meyer mortality analyses were based on nominal concentrations. Animals were exposed to the dissolved fraction of the oil and to the oil droplets (ranging from 14.0 μm to 42.3 μm for the chemical dispersions). Kaplan-Meyer analyses demonstrated an increased mortality in the case of chemical dispersions. This difference can be attributed mainly to differences in TPH, because the chemical lethal concentrations were not reduced compared with mechanical lethal concentrations (except after 24 h of exposure). The ratios of lethal concentrations of mechanical dispersions to the different chemical dispersions were calculated to allow direct comparisons of the relative toxicities of the dispersions. The results ranged from 0.27 to 3.59, with a mean ratio close to 1 (0.92). These results demonstrate an absence of synergistic effect between oil and chemical dispersants in an operational context. PMID:25677812

  3. [A case of summer-type hypersensitivity pneumonitis with bronchoalveolar lavage performed 4 years before onset].

    PubMed

    Saijo, A; Sugiyama, Y; Sugama, Y; Kitamura, S

    1990-08-01

    A 51-year-old man with chief complaints of cough, fever, and dyspnea was admitted to our hospital. Based on a home provocation test, transbronchial lung biopsy specimens, and a serum antibody, we diagnosed summer-type hypersensitivity pneumonitis. In 1983 when the patient was 46 years old, thymectomy was performed for thymoma. Prior to surgery, bronchoalveolar lavage (BAL) was performed. Total cell count and neutrophils had already increased in BALF. Furthermore, the increase in BALF cell neutrophil count was also seen at the time of admission and after the home provocation test. Because an increase of neutrophils in BALF cells was seen not only at onset but before onset, further studies are required to clarify the role of neutrophils and the factors that increase them in hypersensitivity pneumonitis. PMID:2243464

  4. Hypersensitivity Pneumonitis in a Housewife Exposed to Aspergillus flavus in Poor Living Conditions: A Case Report.

    PubMed

    Fernandes, Lalita; 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

  5. Amiodarone-Induced Lung Injury With Bilateral Lung Pneumonitis and Peripheral Eosinophilia.

    PubMed

    Alqaid, Ammar; Baskaran, Gautam; Dougherty, Christopher

    2016-01-01

    Amiodarone is a widely used antiarrhythmic that is used in the management of a variety of atrial and ventricular arrhythmias. Amiodarone-induced lung injury is an adverse effect in 5% of patients taking amiodarone, usually within 12 months of commencing therapy. Different mechanisms of injury and histopathological changes have been proposed and described. Eosinophilic pneumonia is one uncommon presentation of amiodarone-induced lung injury. The following is a case report of a 62-year-old woman who, after taking 400 mg of amiodarone twice daily for 8 months, developed bilateral interstitial pneumonitis with peripheral eosinophilia. After cessation of amiodarone, she had significant improvement in terms of her clinical symptoms and partial regression of pulmonary infiltrates on radiological imaging. The case underlies the importance of vigilance monitoring patients who are taking potentially pneumotoxic drugs as well as describing a classic example of drug-induced pneumonitis. PMID:25882273

  6. Aspiration Pneumonitis Caused by Polyethylene Glycol-Electrolyte Solution Treated with Conservative Management

    PubMed Central

    Mosquera, Ricardo A.; McDonald, Mark; Samuels, Cheryl

    2014-01-01

    Polyethylene glycol (PEG) electrolyte solution, Golytely, is an osmotic laxative commonly used in preoperative bowel cleansing. In this case report, a 9-year-old boy developed aspiration pneumonitis following accidental infusion of PEG solution into his right lung following migration of his nasogastric tube (NGT). Hypoxemia and tachypnea without respiratory failure were observed after infusion. Because PEG is a nonabsorbable toxic material, previous case reports have advocated for the performance of bronchoalveolar lavage (BAL) in the treatment of PEG pneumonitis. With close monitoring, our patient was able to be successfully treated without the need for invasive interventions including BAL or intubation. Generalizations about PEG absorption in the lung based on its permeability in the gastrointestinal tract should not deter the use of more conservative treatment in the appropriate patient. PMID:24955273

  7. Hypersensitivity Pneumonitis in a Housewife Exposed to Aspergillus flavus in Poor Living Conditions: A Case Report

    PubMed Central

    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

  8. Septic shock, necrotizing pneumonitis, and meningoencephalitis caused by Mycoplasma pneumoniae in a child: a case report.

    PubMed

    Barreira, Eliane R; Souza, Daniela C; Góes, Patricia F; Bousso, Albert

    2009-04-01

    Mycoplasma pneumoniae is an important causative agent of respiratory infection in childhood. Although the infection caused by M. pneumoniae is classically described as benign, severe and life-threatening pulmonary and extrapulmonary complications can occur. This study describes the first case of septic shock related to M. pneumoniae in a child with necrotizing pneumonitis, severe encephalitis, and multiple organs involvement, with a favorable outcome after lobectomy and systemic corticosteroids. PMID:19023109

  9. SIMULTANEOUS MULTIPLE SPECIES TESTING: ACUTE TOXICITY OF 13 CHEMICALS TO 12 DIVERSE FRESHWATER AMPHIBIAN, FISH, AND INVERTEBRATE FAMILIES

    EPA Science Inventory

    The test series developed methods for testing a compliment of aquatic organisms in a single test that satisfies the freshwater acute toxicity requirements for setting water quality criteria. Species tested included fathead minnows Pimephales promelas, rainbow trout Salmo gairdner...

  10. The added value of the 90-day repeated dose oral toxicity test for industrial chemicals with a low (sub)acute toxicity profile in a high quality dataset.

    PubMed

    Taylor, Katy; Andrew, David J; Rego, Laura

    2014-08-01

    A survey conducted on the EU Notification of New Substances (NONS) database suggested that for industrial chemicals with a profile of low toxicity in (sub)acute toxicity tests there is little added value to the conduct of the 90-day repeated dose study. Avoiding unnecessary animal testing is a central aim of the EU REACH chemicals legislation; therefore we sought to verify the profile using additional data. The OECD's eChemPortal was searched for substances that had both a 28-day and a 90-day study and their robust study summaries were then examined from the ECHA CHEM database. Out of 182 substances with high quality 28-day and 90-day study results, only 18 reported no toxicity of any kind in the (sub)acute tests. However, for 16 of these there were also no reported signs of toxicity at or close to the limit dose (1000mg/kgbw/d) in the 90-day study. Restricting the 'low (sub)acute toxicity in a high quality dataset' profile to general industrial chemicals of no known biological activity, whilst allowing irritant substances, increases the data set and improves the prediction to 95% (20 substances out of 21 substances). The low toxicity profile appears to be of low prevalence within industrial chemicals (10-15%), nevertheless, avoidance of the conduct of a redundant 90-day study for this proportion of the remaining REACH phase-in substances would avoid the use of nearly 50,000 animals and save industry 50million Euros, with no impact on the assessment of human health. PMID:24768988

  11. The Yersiniabactin Transport System Is Critical for the Pathogenesis of Bubonic and Pneumonic Plague▿

    PubMed Central

    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

  12. Interstitial pneumonitis associated with pegylated interferon alpha-2b therapy for chronic hepatitis C: case report.

    PubMed

    Carrillo-Esper, Raúl; González-Avila, Daniela; Uribe-Ríos, Marittza; Méndez-Sánchez, Nahum

    2008-01-01

    Since 2004, pegylated interferon (P-IFN) in combination with ribavirin has become the optimal choice of therapy for chronic hepatitis C virus (HCV) infection. IFN a-2b suppresses HCV replication and restores elevated serum aminotransferase levels, leading to improvements in the histological changes in the livers of patients with chronic hepatitis C. Unfortunately, P-IFN has several adverse effects, including pneumonitis. This complication has been reported in the treatment of malignant diseases and CHC. We report a patient with interstitial pneumonitis thought to be caused by an IFN-based treatment in an unusual scenario of a patient with HCV-related Child-Pugh stage A cirrhosis, who experienced dyspnea, fever, and cough after 12 months of treatment with P-IFN a-2b. Her lung injury and pulmonary symptoms did not disappear despite discontinuation of IFN and the administration of corticosteroid. We concluded that the patient developed a fatal interstitial pneumonitis associated with P-INF a-2b therapy. PMID:18376374

  13. Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination

    PubMed Central

    Derbise, Anne; Hanada, Yuri; Khalifé, Manal; Carniel, Elisabeth; Demeure, Christian E.

    2015-01-01

    Background 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. Methodology/Principal Findings 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. Significance 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

  14. Comparing the potency of chemicals with multiple modes of action in aquatic toxicology: Acute toxicity due to narcosis versus reactive toxicity of acrylic compounds

    SciTech Connect

    Freidig, A.P.; Verhaar, H.J.M.; Hermens, J.L.M.

    1999-09-01

    A series of acrylates and methacrylates was used to illustrate a strategy to compare the importance of two modes of action (MOA) and thereby identify the predominant cause of acute fish toxicity. Acrylic compounds are known to be Michael acceptors and may therefore react with glutathione (GSH), causing GSH-depletion in vivo (reactive mechanism). On the other hand, acrylates may also act by a nonspecific mechanism (narcosis). The following two, physiologically meaningful parameters were calculated in order to estimate the contribution of these two mechanisms to the overall acute toxicity: (i) a lipid normalized body burden for narcosis and (ii) the potential degree of GSH depletion by chemical reactivity. The degree of GSH depletion was found to be related to the product of the reactivity toward GSH and the exposure concentration. This model was validated with four model compounds and an in vivo study. For both MOA, toxic ratios were calculated and compared for all chemicals in the series. The approach enables the comparison of the contribution to toxicity of chemicals with more than on MOA.

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

    PubMed Central

    Pinnix, Chelsea C.; Smith, Grace L.; Milgrom, Sarah; Osborne, Eleanor M.; Reddy, Jay P.; Akhtari, Mani; Reed, Valerie; Arzu, Isidora; Allen, Pamela K.; Wogan, Christine F.; Fanale, Michele A.; Oki, Yasuhiro; Turturro, Francesco; Romaguera, Jorge; Fayad, Luis; Fowler, Nathan; Westin, Jason; Nastoupil, Loretta; Hagemeister, Fredrick B.; Rodriguez, Alma; Ahmed, Sairah; Nieto, Yago; Dabaja, Bouthaina

    2015-01-01

    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 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 per the Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ2 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 grade 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 (10%, P=0.019). Several dosimetric parameters predicted RP, including mean lung dose (MLD) >13.5 Gy, V20 >30%, V15 >35%, V10 >40% and V5>55%. The likelihood ratio (LR) χ2 value was highest for V5< 55% (LR χ2=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 or refractory lymphoma who received salvage chemotherapy and hematopoietic stem cell

  16. Acute and subacute idiopathic interstitial pneumonias.

    PubMed

    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. PMID:27123874

  17. Acute toxicity of six freshwater mussel species (Glochidia) to six chemicals: Implications for daphnids and Utterbackia imbecillis as surrogates for protection of freshwater mussels (Unionidae)

    USGS Publications Warehouse

    Milam, C.D.; Farris, J.L.; Dwyer, F.J.; Hardesty, D.K.

    2005-01-01

    Acute (24-h) toxicity tests were used in this study to compare lethality responses in early life stages (glochidia) of six freshwater mussel species, Leptodea fragilis, U. imbecillis, Lampsilis cardium, Lampsilis siliquoidea, Megalonaias nervosa, and Ligumia subrostrata, and two standard test organisms, Ceriodaphnia dubia and Daphnia magna. Concentrations of carbaryl, copper, 4-nonylphenol, pentachlorophenol, permethrin, and 2,4-D were used in acute exposures to represent different chemical classes and modes of action. The relative sensitivities of species were evaluated by ranking their LC 50 values for each chemical. We used these ranks to determine the extent to which U. imbecillis (one of the most commonly used unionids in toxicity tests) was representative of the tolerances of other mussels. We also calculated geometric mean LC50s for the families Unionidae and Daphnidae. Rankings of these data were used to assess the extent to which Daphnidae can be used as surrogates for freshwater mussels relative to chemical sensitivity. While no single chemical elicited consistently high or low toxicity estimates, carbaryl and 2,4-D were generally the least toxic to all species tested. No species was always the most sensitive, and Daphnidae were generally protective of Unionidae. Utterbackia imbecillis, while often proposed as a standard unionid mussel test species, did not always qualify as a sufficient surrogate (i.e., a substitute organism that often elicits similar sensitivity responses to the same contaminant exposure) for other species of mussels, since it was usually one of the more tolerant species in our rankings. U. imbecillis should be used as a surrogate species only with this caution on its relative insensitivity. ?? 2005 Springer Science+Business Media, Inc.

  18. An Improved Model for Predicting Radiation Pneumonitis Incorporating Clinical and Dosimetric Variables;Lung cancer; Radiation pneumonitis; Dose-volume histogram; Angiotensin converting enzyme inhibitor

    SciTech Connect

    Jenkins, Peter; Watts, Joanne

    2011-07-15

    Purpose: Single dose-volume metrics are of limited value for the prediction of radiation pneumonitis (RP) in day-to-day clinical practice. We investigated whether multiparametric models that incorporate clinical and physiologic factors might have improved accuracy. Methods and Materials: The records of 160 patients who received radiation therapy for non-small-cell lung cancer were reviewed. All patients were treated to the same dose and with an identical technique. Dosimetric, pulmonary function, and clinical parameters were analyzed to determine their ability to predict for the subsequent development of RP. Results: Twenty-seven patients (17%) developed RP. On univariate analysis, the following factors were significantly correlated with the risk of pneumonitis: fractional volume of lung receiving >5-20 Gy, absolute volume of lung spared from receiving >5-15 Gy, mean lung dose, craniocaudal position of the isocenter, transfer coefficient for carbon monoxide (KCOc), total lung capacity, coadministration of angiotensin converting enzyme inhibitors, and coadministration of angiotensin receptor antagonists. By combining the absolute volume of lung spared from receiving >5 Gy with the KCOc, we defined a new parameter termed Transfer Factor Spared from receiving >5 Gy (TFS{sub 5}). The area under the receiver operator characteristic curve for TFS{sub 5} was 0.778, increasing to 0.846 if patients receiving modulators of the renin-angiotensin system were excluded from the analysis. Patients with a TFS{sub 5} <2.17 mmol/min/kPa had a risk of RP of 30% compared with 5% for the group with a TFS{sub 5} {>=}2.17. Conclusions: TFS{sub 5} represents a simple parameter that can be used in routine clinical practice to more accurately segregate patients into high- and low-risk groups for developing RP.

  19. Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

    PubMed Central

    Hernández-Juviel, José M.; Gordon, Larry M.; Waring, Alan J.

    2014-01-01

    Background. Chemical spills are on the rise and inhalation of toxic chemicals may induce chemical acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Although the pathophysiology of ALI/ARDS is well understood, the absence of specific antidotes has limited the effectiveness of therapeutic interventions. Objectives. Surfactant inactivation and formation of free radicals are important pathways in (chemical) ALI. We tested the potential of lipid mixtures with advanced surfactant protein B and C (SP-B and C) mimics to improve oxygenation and lung compliance in rabbits with lavage- and chemical-induced ALI/ARDS. Methods. Ventilated young adult rabbits underwent repeated saline lung lavages or underwent intratracheal instillation of hydrochloric acid to induce ALI/ARDS. After establishment of respiratory failure rabbits were treated with a single intratracheal dose of 100 mg/kg of synthetic surfactant composed of 3% Super Mini-B (S-MB), a SP-B mimic, and/or SP-C33 UCLA, a SP-C mimic, in a lipid mixture (DPPC:POPC:POPG 5:3:2 by weight), the clinical surfactant Infasurf®, a bovine lung lavage extract with SP-B and C, or synthetic lipids alone. End-points consisted of arterial oxygenation, dynamic lung compliance, and protein and lipid content in bronchoalveolar lavage fluid. Potential mechanism of surfactant action for S-MB and SP-C33 UCLA were investigated with captive bubble surfactometry (CBS) assays. Results. All three surfactant peptide/lipid mixtures and Infasurf equally lowered the minimum surface tension on CBS, and also improved oxygenation and lung compliance. In both animal models, the two-peptide synthetic surfactant with S-MB and SP-C33 UCLA led to better arterial oxygenation and lung compliance than single peptide synthetic surfactants and Infasurf. Synthetic surfactants and Infasurf improved lung function further in lavage- than in chemical-induced respiratory failure, with the difference probably due to greater capillary-alveolar protein

  20. Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury.

    PubMed

    Walther, Frans J; Hernández-Juviel, José M; Gordon, Larry M; Waring, Alan J

    2014-01-01

    Background. Chemical spills are on the rise and inhalation of toxic chemicals may induce chemical acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Although the pathophysiology of ALI/ARDS is well understood, the absence of specific antidotes has limited the effectiveness of therapeutic interventions. Objectives. Surfactant inactivation and formation of free radicals are important pathways in (chemical) ALI. We tested the potential of lipid mixtures with advanced surfactant protein B and C (SP-B and C) mimics to improve oxygenation and lung compliance in rabbits with lavage- and chemical-induced ALI/ARDS. Methods. Ventilated young adult rabbits underwent repeated saline lung lavages or underwent intratracheal instillation of hydrochloric acid to induce ALI/ARDS. After establishment of respiratory failure rabbits were treated with a single intratracheal dose of 100 mg/kg of synthetic surfactant composed of 3% Super Mini-B (S-MB), a SP-B mimic, and/or SP-C33 UCLA, a SP-C mimic, in a lipid mixture (DPPC:POPC:POPG 5:3:2 by weight), the clinical surfactant Infasurf(®), a bovine lung lavage extract with SP-B and C, or synthetic lipids alone. End-points consisted of arterial oxygenation, dynamic lung compliance, and protein and lipid content in bronchoalveolar lavage fluid. Potential mechanism of surfactant action for S-MB and SP-C33 UCLA were investigated with captive bubble surfactometry (CBS) assays. Results. All three surfactant peptide/lipid mixtures and Infasurf equally lowered the minimum surface tension on CBS, and also improved oxygenation and lung compliance. In both animal models, the two-peptide synthetic surfactant with S-MB and SP-C33 UCLA led to better arterial oxygenation and lung compliance than single peptide synthetic surfactants and Infasurf. Synthetic surfactants and Infasurf improved lung function further in lavage- than in chemical-induced respiratory failure, with the difference probably due to greater capillary-alveolar protein

  1. The acute toxicity of chemically and physically dispersed crude oil to key arctic species under arctic conditions during the open water season

    PubMed Central

    Gardiner, William W; Word, Jack Q; Word, Jack D; Perkins, Robert A; McFarlin, Kelly M; Hester, Brian W; Word, Lucinda S; Ray, Collin M

    2013-01-01

    The acute toxicity of physically and chemically dispersed crude oil and the dispersant Corexit 9500 were evaluated for key Arctic species. The copepod Calanus glacialis, juvenile Arctic cod (Boreogadus saida), and larval sculpin (Myoxocephalus sp.) were tested under conditions representative of the Beaufort and Chukchi Seas during the ice-free season. The toxicity of 3 water-accommodated fractions (WAF) of Alaska North Slope crude oil was examined with spiked, declining exposures. A dispersant-only test was conducted with the copepod C. glacialis. Each preparation with oil (WAF, breaking wave WAF [BWWAF], and chemically enhanced WAF [CEWAF]) produced distinct suites of hydrocarbon constituents; the total concentrations of oil were lowest in WAF and highest in CEWAF preparations. The relative sensitivity for the different species and age classes was similar within each WAF type. Median lethal concentration values based on total petroleum hydrocarbons ranged from 1.6 mg/L to 4.0 mg/L for WAF and BWWAF treatments and from 22 mg/L to 62 mg/L for CEWAF. For Corexit 9500 exposures, median lethal concentration values ranged from 17 mg/L to 50 mg/L. The differences in the relative toxicity among the accommodated fractions indicated that the majority of petroleum hydrocarbons in the CEWAF are in less acutely toxic forms than the components that dominate the WAF or BWWAF. Further evaluation showed that the parent polycyclic aromatic hydrocarbon compounds, specifically naphthalene, were highly correlated to acute toxicity. Environ Toxicol Chem 2013;32:2284–2300. PMID:23765555

  2. Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis.

    PubMed

    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 < .0001) and less likely to have an underlying condition not typically associated with lung disease (3% vs 20%, P < .0001). Histopathology was performed in only 17.3% of CMV-positive bronchoscopy episodes. When CMV diagnostic methods were evaluated against the comprehensive 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. PMID:26885542

  3. Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis

    PubMed Central

    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 < .0001) and less likely to have an underlying condition not typically associated with lung disease (3% vs 20%, P < .0001). Histopathology was performed in only 17.3% of CMV-positive bronchoscopy episodes. When CMV diagnostic methods were evaluated against the comprehensive 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. PMID:26885542

  4. Phenotypes of infiltrating cells in trehalose dimycolate-induced interstitial pneumonitis.

    PubMed Central

    Sakamoto, Y; Goren, M B; Kirkpatrick, C H

    1989-01-01

    Trehalose dimycolate is a glycolipid component of the cell walls of mycobacteria, nocardia, and corynebacteria. When trehalose dimycolate is injected into certain strains of mice, they develop interstitial pneumonitis that is characterized by mononuclear cell infiltration of the alveolar walls, intra-alveolar hemorrhages, and in some animals, granuloma formation. The disorder is seldom fatal, and in approximately 4 weeks, the lungs are normal. There is strong evidence that T lymphocytes are essential for production of interstitial pneumonitis by trehalose dimycolate, but little is known about the mechanisms of lung injury in this model. The experiments described in this report were conducted to identify the roles of the various cells that accumulate in the lungs of mice with this form of interstitial pneumonitis. We found that Mac3+ macrophages were the first cells to appear in the alveolar walls. Increases in the number of L3T4+ T lymphocytes, Lyt2+ T lymphocytes, and surface-immunoglobulin-positive lymphocytes followed, but significant increases in the number of lymphoid cells were not observed until day 7, when the pulmonary lesions were well developed. Treatment of the mice with cyclophosphamide or anti-T-cell sera significantly reduced the number of lymphoid cells in the alveolar walls but did not affect the number of Mac3+ cells and did not affect development of intra-alveolar hemorrhages. Treatment with poly(I.C) significantly decreased the number of Mac3+ cells in the lungs, and these mice did not develop pulmonary hemorrhages. We conclude that although development of pulmonary lesions in trehalose dimycolate-treated mice is a T-cell-dependent process, macrophages are also essential and are more directly involved in production of the lung injury. We postulate that the lung lesions are the direct effect of macrophage-produced cytokines, such as tumor necrosis factor. Images PMID:2731985

  5. Using patient data similarities to predict radiation pneumonitis via a self-organizing map

    NASA Astrophysics Data System (ADS)

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

    2008-01-01

    This work investigates the use of the self-organizing map (SOM) technique for predicting lung radiation pneumonitis (RP) risk. SOM is an effective method for projecting and visualizing high-dimensional data in a low-dimensional space (map). By projecting patients with similar data (dose and non-dose factors) onto the same region of the map, commonalities in their outcomes can be visualized and categorized. Once built, the SOM may be used to predict pneumonitis risk by identifying the region of the map that is most similar to a patient's characteristics. Two SOM models were developed from a database of 219 lung cancer patients treated with radiation therapy (34 clinically diagnosed with Grade 2+ pneumonitis). The models were: SOMall built from all dose and non-dose factors and, for comparison, SOMdose built from dose factors alone. Both models were tested using ten-fold cross validation and Receiver Operating Characteristics (ROC) analysis. Models SOMall and SOMdose yielded ten-fold cross-validated ROC areas of 0.73 (sensitivity/specificity = 71%/68%) and 0.67 (sensitivity/specificity = 63%/66%), respectively. The significant difference between the cross-validated ROC areas of these two models (p < 0.05) implies that non-dose features add important information toward predicting RP risk. Among the input features selected by model SOMall, the two with highest impact for increasing RP risk were: (a) higher mean lung dose and (b) chemotherapy prior to radiation therapy. The SOM model developed here may not be extrapolated to treatment techniques outside that used in our database, such as several-field lung intensity modulated radiation therapy or gated radiation therapy.

  6. Amiodarone-induced pulmonary toxicity mimicking acute pulmonary edema.

    PubMed

    Fabiani, Iacopo; Tacconi, Danilo; Grotti, Simone; Brandini, Rossella; Salvadori, Claudia; Caremani, Marcello; Bolognese, Leonardo

    2011-05-01

    Amiodarone is a highly effective antiarrhythmic drug. Its long-term use may, however, lead to several adverse effects, with pulmonary toxicity being the most serious. The article presents the case of a 78-year-old woman with a history of cardiac surgery, who after 2 years of amiodarone therapy for prophylactic treatment of atrial fibrillation developed amiodarone pneumonitis mimicking an acute pulmonary edema. The patient failed to respond to diuretic therapy and several courses of anti-infective therapy. Differential diagnosis of different causes of pulmonary infiltrates did not demonstrate any other abnormality. Lung biopsy findings were consistent with the diagnosis of amiodarone pneumonitis. Given the widespread use of amiodarone as an antiarrhythmic agent, pneumologists and cardiologists should consider this important adverse effect as a differential diagnosis of pulmonary distress refractory to therapy in all patients treated with amiodarone who present with respiratory symptoms and pneumonia-like illness. PMID:19924000

  7. Hypersensitivity Pneumonitis: Challenges in Diagnosis and Management, Avoiding Surgical Lung Biopsy.

    PubMed

    Morell, Ferran; Villar, Ana; Ojanguren, Iñigo; Muñoz, Xavier; Cruz, María-Jesús

    2016-06-01

    This review presents an update of the currently available information related to hypersensitivity pneumonitis, with a particular focus on the contribution of several techniques in the diagnosis of this condition. The methods discussed include proper elaboration of a complete medical history, targeted auscultation, detection of specific immunoglobulin G antibodies against the most common antigens causing this disease, skin tests, antigen-specific lymphocyte activation assays, bronchoalveolar lavage, and cryobiopsy. Special emphasis is placed on the relevant contribution of specific inhalation challenge (bronchial challenge test). Surgical lung biopsy is presented as the ultimate recourse, to be used when the diagnosis cannot be reached through the other methods covered. PMID:27231863

  8. Pneumonia carcinomatosa from small cell undifferentiated carcinoma of the lung presenting as reverse radiation pneumonitis

    SciTech Connect

    Adelstein, D.J.; Padhya, T.; Tomashefski, J.F. Jr.; Park, C.

    1988-01-01

    We describe a patient with recurrent small cell undifferentiated lung carcinoma after chemotherapy and mediastinal radiation therapy who presented with peripheral pulmonary infiltrates on chest radiograph. At autopsy the patient was found to have carcinomatous pneumonia confined to the radiographically abnormal lung. The descriptive term reverse radiation pneumonitis is applied in view of the striking nonsegmental distribution of these pulmonary infiltrates, which occurred only outside the irradiated field. In this patient, radiation therapy successfully controlled disease in the treated lung parenchyma, thus accounting for this unusual radiologic and histologic picture. Pneumonia carcinomatosa, occurring after lung irradiation, can therefore be added to the differential diagnosis of radiographic peripheral pulmonary infiltrates.

  9. Procarbazine-induced interstitial pneumonitis with a normal chest x-ray: a case report

    SciTech Connect

    Garbes, I.D.; Henderson, E.S.; Gomez, G.A.; Bakshi, S.P.; Parthasarathy, K.L.; Castillo, N.B.

    1986-01-01

    Pulmonary toxicity due to cytotoxic drugs is well described in the literature. This is most commonly described in association with bleomycin, busulfan, and methotrexate. This report presents a case of interstitial pneumonitis with a normal chest x-ray that is most certainly due to procarbazine. In addition, the role of gallium-67 citrate scintigraphy in early diagnosis is discussed. This is especially important since discontinuation of the drug before radiographic manifestations of pulmonary toxicity become evident may prevent permanent pulmonary injury and its sequelae.

  10. Administration of a synthetic TLR4 agonist protects mice from pneumonic tularemia.

    PubMed

    Lembo, Annalisa; Pelletier, Mark; Iyer, Ravi; Timko, Michele; Dudda, Jan C; West, T Eoin; Wilson, Christopher B; Hajjar, Adeline M; Skerrett, Shawn J

    2008-06-01

    Francisella tularensis is a Gram-negative intracellular pathogen that causes the zoonosis tularemia. Because F. tularensis LPS causes weak TLR4 activation, we hypothesized that administration of a synthetic TLR4 agonist, aminoalkyl glucosaminide phosphate (AGP), would boost the innate immune system and compensate for reduced TLR4 stimulation. Intranasal administration of AGPs induced intrapulmonary production of proinflammatory cytokines and chemokines. Mice treated with AGPs before and after inhalation of Francisella novicida exhibited augmented cytokine and inflammatory responses to infection; reduced bacterial replication in lung, liver, and spleen; and increased survival, whereas all PBS-treated control mice died within 4 days of infection, all AGP-treated mice showed prolonged time-to-death, and 30-60% of AGP-treated mice survived. The protective effect of AGP was lost in mice lacking IFN-gamma. Long-term survivors developed specific Th1 splenocyte responses and specific Abs dominated by IgG2 isotypes. Survivors were fully protected from rechallenge with aerosolized F. novicida. Thus, preventive administration of AGP successfully modulated innate immune responses to aerosolized F. novicida, leading to protective immunity to pneumonic tularemia. This is the first report of the protective effect of a TLR ligand on resistance to F. novicida-induced pneumonic tularemia. PMID:18490759

  11. Validation and optimization of a predictive model for radiation pneumonitis in patients with lung cancer

    PubMed Central

    Mörth, Charlott; Kafantaris, Ioannis; Castegren, Markus; Valachis, Antonios

    2016-01-01

    The aim of the current retrospective study was to validate a predictive model for radiation pneumonitis (STRIPE) in an independent dataset and to investigate whether the addition of other potential risk factors could strengthen the accuracy of the model. Consecutive patients with non-small cell lung carcinoma (NSCLC; n=71) treated with definitive concurrent chemotherapy and radiotherapy were retrospectively assessed for radiation pneumonitis (RP). The results identified that 16 (23%) patients developed grade ≥2 RP. Furthermore, STRIPE score (intermediate vs. low risk) was independently associated with the development of RP [odds ratio (OR), 3.72; 95% confidence interval (CI), 1.00–13.89], whereas current smoking status was found to be protective against RP (OR, 0.09; 95% CI, 0.01–0.78). Similar discriminatory power of the STRIPE score was observed as in the original study. The addition of smoking status strengthened the model's discriminatory ability to predict RP. Thus, the addition of smoking status as a risk factor may strengthen the accuracy of the model for predicting RP in patients with NSCLC. PMID:27446409

  12. Nivolumab-induced organizing pneumonitis in a patient with lung sarcomatoid carcinoma.

    PubMed

    Gounant, V; Brosseau, S; Naltet, C; Opsomer, M-A; Antoine, M; Danel, C; Khalil, A; Cadranel, J; Zalcman, G

    2016-09-01

    Immune checkpoint inhibitors are known to induce 'immune pneumonitis' in 3-6% of patients treated for lung cancer. However, their dramatic efficacy in as much as 20% of patients led to recent registrations in squamous, and then non-squamous lung carcinoma, in second line setting after failure of first-line chemotherapy, while large phase 3 trials are on-going, to assess first-line immunotherapy, either alone or in combination with chemotherapy. Pulmonary Sarcomatoid carcinomas consist of a rare subset of highly aggressive and poorly differentiated non-small-cell lung carcinomas (NSCLC), with poor prognosis and chemo-resistance. Although exhibiting high expression of programmed death ligand-1 (PD-L1), their sensitivity to inhibitors of PD-1/PD-L1 axis is still unknown. Here we report a case of lung sarcomatoid carcinoma with Nivolumab dramatic and long-lasting efficacy, but occurrence of a very specific pattern of lung toxicity, the so-called 'organizing bronchiolitis syndrome'. As more and more NSCLC patients are promised to receive PD-1 inhibitors as part of their treatment, we feel that specific features of such Nivolumab-induced organizing pneumonitis should be known. Although corticosteroid sensitivity is high, recurrence is frequent because of premature steroid tapering, as for all other causes of organizing pneumonias, and probably because of the Nivolumab long tissue half-life. PMID:27565934

  13. Induction of immunity against pneumonic pasteurellosis following experimental infection in calves.

    PubMed Central

    Cho, H J; Jericho, K W

    1986-01-01

    Immunity against pneumonic pasteurellosis was studied in calves after recovery from experimental respiratory disease with Pasteurella haemolytica. Nine calves were exposed to aerosols of parainfluenza-3 virus and Pasteurella haemolytica A1 six days apart to produce respiratory disease. After recovery from the disease, these nine principal and four control calves were challenged with aerosols of bovine herpesvirus 1 and P. haemolytica A1 four days apart. With this viral-bacterial challenge, the nine principal animals failed to develop clinical responses to this bacterial challenge and their lungs did not show the growth of P. haemolytica on cultures, whereas two of four control calves had elevated temperatures and developed necropurulent pneumonia with the isolation of P. haemolytica from the lungs. The principal calves had developed high levels of cytotoxin neutralizing antibodies in their sera following parainfluenza-3 virus-P. haemolytica infection. This demonstrated that immunity against pneumonic pasteurellosis can be achieved, with a suggestion that further search for an effective vaccine for P. haemolytica is warranted. PMID:3017526

  14. [A case of chronic hypersensitivity pneumonitis induced by shiitake mushroom spores].

    PubMed

    Fujiwara, K; Sato, T; Yonei, T; Genba, K; Nogami, N; Yamadori, I

    2000-12-01

    A 73-year-old woman was admitted to our hospital with a low-grade fever, dry cough and dyspnea on exertion as the chief complaints. She had been a professional shiitake mushroom grower for 50 years. Three years before visiting our hospital, she had been suspected of having hypersensitivity pneumonitis as a result of chest X-ray examination, bronchoalveolar lavage and transbronchial lung biopsy performed at another clinic. No antigens were identified at that time, but prednisolone was administered. On admission to our hospital, chest radiography and chest computed tomography revealed an interstitial shadow with subpleural honey-combing in both lower lung fields. After steroid pulse therapy, dyspnea on exertion and hypoxia improved moderately. Because of recurrence of the dyspnea, however, she was admitted on four separate occasions. On the second admission, an increase in lymphocytes was found by bronchoalveolar lavage, and septal lymphocytic infiltration accompanying fibrosis was demonstrated by transbronchial lung biopsy. On the fourth admission, a detailed immunological examination and an environmental survey were performed. The environmental provocation test yielded clinical symptoms similar to those experienced at the mushroom farm. Furthermore, tests of precipitation and lymphocyte proliferation in response to shiitake mushroom extracts were positive. Finally a diagnosis of chronic hypersensitivity pneumonitis induced by shiitake mushrooms was confirmed. PMID:11244726

  15. Impact of the Pla protease substrate α2-antiplasmin on the progression of primary pneumonic plague.

    PubMed

    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. PMID:26438794

  16. [Evaluation of the treat of acute poisoning with chemical compounds among adult inhabitants of Krakow in 1995].

    PubMed

    Kamenczak, A; Pach, K; Kłys, M; Motyka, E

    1997-01-01

    The goal of this study is to evaluate the number and the reasons (poison and structure) of acute poisonings which occurred among Kraków adult inhabitants in the year 1995. Under analysis there were 3003 people treated at the Department of Clinical Toxicology and 210 poisoned who died at the place of accident prior to any treatment was conducted. The group of hospitalized persons consisted of 63.7% men and 36.3% women, and the group of people who died at the place of accident consisted of 89.5% men and of 10.5% women. The overall coefficient of poisonings during the year 1995 was 48.3; for men was 66.7 and 32.5 for women. A drugs (45.1%) followed by ethanol (42.8%) were the most common cause of acute poisonings. The mortality rate of the treated patients was low (0.7%), but while including those people who died at the place of accident prior to any treatment, the mortality rate rose up to 7.2%. That increase in the mortality rate was caused mainly by fatal cases due to ethanol and carbon monoxide poisonings. PMID:9333887

  17. Chemically Diverse Group I p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window.

    PubMed

    Rudolph, Joachim; Murray, Lesley J; Ndubaku, Chudi O; O'Brien, Thomas; Blackwood, Elizabeth; Wang, Weiru; Aliagas, Ignacio; Gazzard, Lewis; Crawford, James J; Drobnick, Joy; Lee, Wendy; Zhao, Xianrui; Hoeflich, Klaus P; Favor, David A; Dong, Ping; Zhang, Haiming; Heise, Christopher E; Oh, Angela; Ong, Christy C; La, Hank; Chakravarty, Paroma; Chan, Connie; Jakubiak, Diana; Epler, Jennifer; Ramaswamy, Sreemathy; Vega, Roxanne; Cain, Gary; Diaz, Dolores; Zhong, Yu

    2016-06-01

    p21-activated kinase 1 (PAK1) has an important role in transducing signals in several oncogenic pathways. The concept of inhibiting this kinase has garnered significant interest over the past decade, particularly for targeting cancers associated with PAK1 amplification. Animal studies with the selective group I PAK (pan-PAK1, 2, 3) inhibitor G-5555 from the pyrido[2,3-d]pyrimidin-7-one class uncovered acute toxicity with a narrow therapeutic window. To attempt mitigating the toxicity, we introduced significant structural changes, culminating in the discovery of the potent pyridone side chain analogue G-9791. Mouse tolerability studies with this compound, other members of this series, and compounds from two structurally distinct classes revealed persistent toxicity and a correlation of minimum toxic concentrations and PAK1/2 mediated cellular potencies. Broad screening of selected PAK inhibitors revealed PAK1, 2, and 3 as the only overlapping targets. Our data suggest acute cardiovascular toxicity resulting from the inhibition of PAK2, which may be enhanced by PAK1 inhibition, and cautions against continued pursuit of pan-group I PAK inhibitors in drug discovery. PMID:27167326

  18. Association between pH-weighted endogenous amide proton chemical exchange saturation transfer MRI and tissue lactic acidosis during acute ischemic stroke.

    PubMed

    Sun, Phillip Zhe; Cheung, Jerry S; Wang, Enfeng; Lo, Eng H

    2011-08-01

    The ischemic tissue becomes acidic after initiation of anaerobic respiration, which may result in impaired tissue metabolism and, ultimately, in severe tissue damage. Although changes in the major cerebral metabolites can be studied using magnetic resonance (MR) spectroscopy (MRS)-based techniques, their spatiotemporal resolution is often not sufficient for routine examination of fast-evolving and heterogeneous acute stroke lesions. Recently, pH-weighted MR imaging (MRI) has been proposed as a means to assess tissue acidosis by probing the pH-dependent chemical exchange of amide protons from endogenous proteins and peptides. In this study, we characterized acute ischemic tissue damage using localized proton MRS and multiparametric imaging techniques that included perfusion, diffusion, pH, and relaxation MRI. Our study showed that pH-weighted MRI can detect ischemic lesions and strongly correlates with tissue lactate content measured by (1)H MRS, indicating lactic acidosis. Our results also confirmed the correlation between apparent diffusion coefficient and lactate; however, no significant relationship was found for perfusion, T(1), and T(2). In summary, our study showed that optimized endogenous pH-weighted MRI, by sensitizing to local tissue pH, remains a promising tool for providing a surrogate imaging marker of lactic acidosis and altered tissue metabolism, and augments conventional techniques for stroke diagnosis. PMID:21386856

  19. Acute Onset Anti-Synthetase Syndrome With Pericardial Effusion and Non-Specific Interstitial Pneumonia

    PubMed Central

    Shah, Aditya; Patel, Samir R.

    2016-01-01

    Anti-synthetase syndrome (AS) is a clinical entity which is described classically by the triad of interstitial lung disease (ILD), inflammatory myositis and presence of aminoacyl-tRNA synthetase antibodies (ASA). We describe a rare presentation of this condition with regard to the uncharacteristically acute nature of presentation, acute decompensation in clinical condition, development of acute interstitial pneumonitis requiring rescue extracorporeal membrane oxygenation (ECMO) and accompaniment of significant pericardial effusion on presentation, followed by rapid improvement with initiation of steroids. PMID:27540445

  20. Acute Onset Anti-Synthetase Syndrome With Pericardial Effusion and Non-Specific Interstitial Pneumonia.

    PubMed

    Shah, Aditya; Patel, Samir R

    2016-09-01

    Anti-synthetase syndrome (AS) is a clinical entity which is described classically by the triad of interstitial lung disease (ILD), inflammatory myositis and presence of aminoacyl-tRNA synthetase antibodies (ASA). We describe a rare presentation of this condition with regard to the uncharacteristically acute nature of presentation, acute decompensation in clinical condition, development of acute interstitial pneumonitis requiring rescue extracorporeal membrane oxygenation (ECMO) and accompaniment of significant pericardial effusion on presentation, followed by rapid improvement with initiation of steroids. PMID:27540445

  1. Pneumonic Tularemia in Rabbits Resembles the Human Disease as Illustrated by Radiographic and Hematological Changes after Infection

    PubMed Central

    Reed, Douglas S.; Smith, Le'Kneitah; Dunsmore, Tammy; Trichel, Anita; Ortiz, Luis A.; Cole, Kelly Stefano; Barry, Eileen

    2011-01-01

    Background Pneumonic tularemia is caused by inhalation of the gram negative bacterium, Francisella tularensis. Because of concerns that tularemia could be used as a bioterrorism agent, vaccines and therapeutics are urgently needed. Animal models of pneumonic tularemia with a pathophysiology similar to the human disease are needed to evaluate the efficacy of these potential medical countermeasures. Principal Findings Rabbits exposed to aerosols containing Francisella tularensis strain SCHU S4 developed a rapidly progressive fatal pneumonic disease. Clinical signs became evident on the third day after exposure with development of a fever (>40.5°C) and a sharp decline in both food and water intake. Blood samples collected on day 4 found lymphopenia and a decrease in platelet counts coupled with elevations in erythrocyte sedimentation rate, alanine aminotransferase, cholesterol, granulocytes and monocytes. Radiographs demonstrated the development of pneumonia and abnormalities of intestinal gas consistent with ileus. On average, rabbits were moribund 5.1 days after exposure; no rabbits survived exposure at any dose (190–54,000 cfu). Gross evaluation of tissues taken at necropsy showed evidence of pathology in the lungs, spleen, liver, kidney and intestines. Bacterial counts confirmed bacterial dissemination from the lungs to the liver and spleen. Conclusions/Significance The pathophysiology of pneumonic tularemia in rabbits resembles what has been reported for humans. Rabbits therefore are a relevant model of the human disease caused by type A strains of F. tularensis. PMID:21931798

  2. Draft Genome Sequence of the Causative Antigen of Summer-Type Hypersensitivity Pneumonitis, Trichosporon domesticum JCM 9580

    PubMed Central

    Cho, Otomi; Ichikawa, Tomoe; Kurakado, Sanae; Takashima, Masako; Manabe, Ri-ichiroh; Ohkuma, Moriya

    2016-01-01

    Here, we report the draft genome sequence of Trichosporon domesticum JCM 9580, isolated from the house of a patient with summer-type hypersensitivity pneumonitis (SHP) in Japan. This genomic information will help elucidate the mechanisms of the development of SHP. PMID:27389271

  3. Acute sensitivity of freshwater mollusks and commonly tested invertebrates to select chemicals with different toxic models of action

    EPA Science Inventory

    Previous studies indicate that freshwater mollusks are more sensitive than commonly tested organisms to some chemicals, such as copper and ammonia. Nevertheless, mollusks are generally under-represented in toxicity databases. Studies are needed to generate data with which to comp...

  4. Impact of Chemical Proportions on the Acute Neurotoxicity of a Mixture of Seven Carbamates in Preweanling and Adult Rats

    EPA Science Inventory

    Statistical design and environmental relevance are important aspects of studies of chemical mixtures, such as pesticides. We used a dose-additivity model to test experimentally the default assumptions of dose-additivity for two mixtures of seven N-methylcarbamates (carbaryl, carb...

  5. Discovery of a Leptospirosis Cluster Amidst a Pneumonic Plague Outbreak in a Miners’ Camp in the Democratic Republic of the Congo

    PubMed Central

    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

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

    SciTech Connect

    Pinnix, Chelsea C.; Smith, Grace L.; Milgrom, Sarah; Osborne, Eleanor M.; Reddy, Jay P.; Akhtari, Mani; Reed, Valerie; Arzu, Isidora; Allen, Pamela K.; Wogan, Christine F.; 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 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

  7. Association Between Pulmonary Uptake of Fluorodeoxyglucose Detected by Positron Emission Tomography Scanning After Radiation Therapy for Non-Small-Cell Lung Cancer and Radiation Pneumonitis

    SciTech Connect

    Mac Manus, Michael P.; Ding Zhe; Hogg, Annette; Herschtal, Alan; Binns, David; Ball, David L.; Hicks, Rodney J.

    2011-08-01

    Purpose: To study the relationship between fluorodeoxyglucose (FDG) uptake in pulmonary tissue after radical radiation therapy (RT) and the presence and severity of radiation pneumonitis. Methods and Materials: In 88 consecutive patients, {sup 18}F-FDG-positron emission tomography was performed at a median of 70 days after completion of RT. Patients received 60 Gy in 30 fractions, and all but 15 had concurrent platinum-based chemotherapy. RT-induced pulmonary inflammatory changes occurring within the radiation treatment volume were scored, using a visual (0 to 3) radiotoxicity grading scale, by an observer blinded to the presence or absence of clinical radiation pneumonitis. Radiation pneumonitis was retrospectively graded using the Radiation Therapy Oncology Group (RTOG) scale by an observer blinded to the PET radiotoxicity score. Results: There was a significant association between the worst RTOG pneumonitis grade occurring at any time after RT and the positron emission tomograph (PET) radiotoxicity grade (one-sided p = 0.033). The worst RTOG pneumonitis grade occurring after the PET scan was also associated with the PET radiotoxicity grade (one-sided p = 0.035). For every one-level increase in the PET toxicity scale, the risk of a higher RTOG radiation pneumonitis score increased by approximately 40%. The PET radiotoxicity score showed no significant correlation with the duration of radiation pneumonitis. Conclusions: The intensity of FDG uptake in pulmonary tissue after RT determined using a simple visual scoring system showed significant correlation with the presence and severity of radiation pneumonitis. {sup 18}F-FDG-PET may be useful in the prediction, diagnosis and therapeutic monitoring of radiation pneumonitis.

  8. PULMONARY AND SYSTEMIC HEALTH EFFECTS OF ACUTE AND SUBCHRONIC EXPOSURE TO SMOKE OBSCURANT SGF-2

    EPA Science Inventory

    Sixty-day old, male rats were exposed to air, 0.5 or 1.5 ml/1 fog-oil for 3.5 hr/d, 4 days/wk for either 4 or 13 wk. Following the acute (4 wk) exposure to 1.5 mg/1, a multifocal pneumonitis was observed. Lung lavage fluid had an elevated number of polymorphonuclear leukocytes, a...

  9. Hypersensitivity pneumonitis

    MedlinePlus

    ... alveolitis; Farmer's lung; Mushroom picker's disease; Humidifier or air-conditioner lung; Bird breeder's or bird fancier's lung ... fungi or bacteria in humidifiers, heating systems, and air conditioners found in homes and offices. Exposure to ...

  10. Pneumonic Plague

    MedlinePlus

    ... direct, close contact with infected patients. Wearing a close-fitting surgical mask also protects against ... October 14, 2001 Content source: Division of Vector-Borne Infectious Diseases (DVBID) , National ...

  11. Interventions at caesarean section for reducing the risk of aspiration pneumonitis

    PubMed Central

    Paranjothy, Shantini; Griffiths, James D; Broughton, Hannah K; Gyte, Gillian ML; Brown, Heather C; Thomas, Jane

    2014-01-01

    Background Aspiration pneumonitis is a syndrome resulting from the inhalation of gastric contents. The incidence in obstetric anaesthesia has fallen, largely due to improved anaesthetic techniques and the increased use of regional anaesthesia at caesarean section. However, aspiration pneumonitis is still a cause of maternal morbidity and mortality, and it is important to use effective prophylaxis. Objectives To determine whether interventions given prior to caesarean section reduce the risk of aspiration pneumonitis in women with an uncomplicated pregnancy. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (April 2009). Selection criteria Randomised controlled trials were included. Quasi-randomised trials were excluded. Data collection and analysis Authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked. Main results Twenty-two studies, involving 2658 women, are included, all having a caesarean section under general anaesthesia. The studies covered a number of comparisons, but were mostly small and of unclear or poor quality. When compared to no treatment or placebo, there was a significant reduction in the risk of intragastric pH < 2.5 with antacids (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.09 to 0.32, two studies, 108 women), H2 antagonists (RR 0.09, 95% CI 0.05 to 0.18, two studies, 170 women) and proton pump antagonists (RR 0.26, 95% CI 0.14 to 0.46, one study 80 women). H2 antagonists were associated with a reduced the risk of intragastric pH < 2.5 at intubation when compared with proton pump antagonists (RR 0.39, 95% CI 0.16 to 0.97, one study, 120 women), but compared with antacids the findings were unclear. The combined use of ’antacids plus H2 antagonists’ was associated with a significant reduction in the risk of intragastric pH < 2.5 at intubation when compared with placebo (RR 0.02, 95% CI 0.00 to 0.15, one study, 89

  12. Pre-radiotherapy FDG PET predicts radiation pneumonitis in lung cancer

    PubMed Central

    2014-01-01

    Background A retrospective analysis is performed to determine if pre-treatment [18 F]-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) image derived parameters can predict radiation pneumonitis (RP) clinical symptoms in lung cancer patients. Methods and Materials We retrospectively studied 100 non-small cell lung cancer (NSCLC) patients who underwent FDG PET/CT imaging before initiation of radiotherapy (RT). Pneumonitis symptoms were evaluated using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4) from the consensus of 5 clinicians. Using the cumulative distribution of pre-treatment standard uptake values (SUV) within the lungs, the 80th to 95th percentile SUV values (SUV80 to SUV95) were determined. The effect of pre-RT FDG uptake, dose, patient and treatment characteristics on pulmonary toxicity was studied using multiple logistic regression. Results The study subjects were treated with 3D conformal RT (n = 23), intensity modulated RT (n = 64), and proton therapy (n = 13). Multiple logistic regression analysis demonstrated that elevated pre-RT lung FDG uptake on staging FDG PET was related to development of RP symptoms after RT. A patient of average age and V30 with SUV95 = 1.5 was an estimated 6.9 times more likely to develop grade ≥ 2 radiation pneumonitis when compared to a patient with SUV95 = 0.5 of the same age and identical V30. Receiver operating characteristic curve analysis showed the area under the curve was 0.78 (95% CI = 0.69 – 0.87). The CT imaging and dosimetry parameters were found to be poor predictors of RP symptoms. Conclusions The pretreatment pulmonary FDG uptake, as quantified by the SUV95, predicted symptoms of RP in this study. Elevation in this pre-treatment biomarker identifies a patient group at high risk for post-treatment symptomatic RP. PMID:24625207

  13. Tissue factor activity. A marker of alveolar macrophage maturation in rabbits. Effects of granulomatous pneumonitis.

    PubMed Central

    Rothberger, H; McGee, M P; Lee, T K

    1984-01-01

    Experiments were carried out to examine relationships between alveolar macrophage maturity and amounts of tissue factor (Clotting Factor III) in these cells under physiologic conditions and during immunologically induced pneumonitis. Using discontinuous density gradient centrifugation, alveolar macrophages from healthy rabbits were rapidly isolated into five subpopulations at different stages of maturation, as demonstrated by morphologic and morphometric evaluation. Very large amounts of tissue factor activity were found in fully mature cells that were purified in the lowest density subpopulation and assayed without preliminary in vitro stimulation or culture. In the remaining four subpopulations of increasing density, amounts of tissue factor were found to progressively diminish in direct correlation with declines of cell maturity. These differences at mean levels were as great as 35-fold. In addition, blood monocytes had less than 1/219 and less than 1/6 of the activity of the fully mature and the least mature subpopulations, respectively. After 16 h culture of the five isolated subpopulations in the absence of lymphokines or of significant numbers of lymphocytes, tissue factor activity increased in inverse correlation with the preincubation stage of cell maturity (2,387 and 109% in the least mature and most mature subpopulations, respectively). These increases required protein synthesis and were accompanied by morphologic and morphometric changes which indicated cellular maturation during the period of tissue factor activity generation in vitro, thus further demonstrating relationships between macrophage maturity and tissue factor content. In additional experiments, direct correlations between cell maturity and tissue factor activity content were also found in activated alveolar macrophage populations from rabbits with Bacillus Calmette Guering (BCG)-induced granulomatous pneumonitis. However, as compared with controls, the BCG populations had increased total

  14. Improving chemotherapeutic efficiency in acute myeloid leukemia treatments by chemically synthesized peptide interfering with CXCR4/CXCL12 axis

    PubMed Central

    Li, Xiaojin; Guo, Hua; Duan, Hongyang; Yang, Yanlian; Meng, Jie; Liu, Jian; Wang, Chen; Xu, Haiyan

    2015-01-01

    Bone marrow stroma can protect acute myeloid leukemia (AML) cells against chemotherapeutic agents and provide anti-apoptosis and chemoresistance signals through secreting chemokine CXCL12 to activate its receptor CXCR4 on AML cells, resulting in minimal residual leukemia and relapse. Therefore disrupting the CXCR4/CXCL12 axis with antagonists is of great significance for improving chemosensitivity and decreasing relapse rate. In a previous study, we reported a novel synthetic peptide E5 with its remarkable effect on inhibiting CXCR4/CXCL12-mediated adhesion and migration of AML cells. Here we presented E5’s capacity of enhancing the therapeutic efficiency of various chemotherapeutics on AML in vitro and in vivo. Results showed that E5 can diminish bone marrow stromal cell-provided protection to leukemia cells, significantly increasing the apoptosis induced by various chemotherapeutics in multiple AML cell lines. In an AML mouse xenograft model, E5 induced 1.84-fold increase of circulating AML cells out of protective stroma niche. Combined with vincristine or cyclophosphamide, E5 inhibited infiltration of AML cells into bone marrow, liver and spleen, as well as prolonged the lifespan of AML mice compared with mice treated with chemotherapy alone. In addition, E5 presented no toxicity in vivo according to the histological analysis and routine clinical parameters of serum analysis. PMID:26538086

  15. Acute poisonings with chemical compounds among adolescent and adult inhabitants of Kraków in the year 1997.

    PubMed

    Sancewicz-Pach, K; Kamenczak, A; Klag, E; Kłys, M

    1999-01-01

    The pattern of adolescent and adult poisonings in Kraków is presented on the basis of the data collected by the Poison Information Centre of the Department of Clinical Toxicology Collegium Medicum of the Jagiellonian University in 1997. This analysis includes 3472 people treated at the Department of Clinical Toxicology and 118 poisoned people who were not given any treatment and died at the scene of the accident. The group of hospitalised persons consisted of 2359 (67.9%) men and 1113 (32.1%) women, and the group of people who died at the scene of the accident consisted of 97 (82.2%) men and of 21 (17.8%) women. The overall coefficient of poisonings in 1997 was 46.9; for men--67.8 and 28.3 for women. Ethanol (39.7%) followed by drugs (20.2%), drugs + ethanol (6.7%), carbon monoxide (6.2%) and drugs of abuse (4.4%) were the most common cause of acute poisonings. The mortality rate of the cases treated was low (0.43%), but while including those people who were not given any treatment and died at the scene of the accident, mostly due to ethanol, carbon monoxide, and drugs poisoning the fatality index rose up to 3.7%. PMID:10465990

  16. Diagnosis of hypersensitivity pneumonitis by measurement of antibodies against environmental antigens

    SciTech Connect

    Dewair, M. )

    1989-01-01

    Hypersensitivity pneumonitis (HP), an immunologically mediated chronic pulmonary disease, is the result of an inflammatory response of the lung initiated by the inhalation of environmental organic dusts. These organic dusts usually contain substances (antigens) capable of eliciting immune responses in humans. The symptoms of HP generally present as recurrent flu-like episodes which makes it difficult to establish the proper diagnosis. However, detection in patients' sera of high-titer antibodies against the environmental antigens could be of great help in identifying those materials causing the disease and which must be avoided. A highly specific and sensitive serodiagnostic test, a radioimmuno assay (RIA), was developed for measurement of antibodies against antigens relevant to Farmer's Lung Disease (FLD), a type of HP affecting farmers.

  17. Epidemiologic investigation of an oil-associated pneumonic paralytic eosinophilic syndrome in Spain.

    PubMed

    Rigau-Pérez, J G; Pérez-Alvarez, L; Dueñas-Castro, S; Choi, K; Thacker, S B; Germain, J L; González-de-Andrés, G; Cañada-Royo, L; Pérez-Gallardo, F

    1984-02-01

    From May 1 to December 26, 1981, a previously undescribed illness caused 277 deaths and the hospitalization of 12,656 persons in Spain. The disease was characterized by pneumonitis, eosinophilia, and marked loss of muscle mass and function. A succession of case-control studies was done in the town of Las Navas del Marqués (province of Avila) located 47 miles northeast of Madrid and with a population of 4009 people. The studies confirmed the association between illness and consumption of an illegally sold cooking oil. Other risk factors identified in the linear logistic regression analysis included involvement in various kitchen activities, increased average time spent inside the house, and the purchase of cooking oil from a specific street vendor. Although the oil was found to be a mixture of vegetable and animal fats contaminated with aniline and anilide-oil complexes, the specific etiologic mechanism of the disease has not been determined. PMID:6695904

  18. Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague

    PubMed Central

    Stasulli, Nikolas M.; Eichelberger, Kara R.; Price, Paul A.; Pechous, Roger D.; Montgomery, Stephanie A.; Parker, Joel S.

    2015-01-01

    ABSTRACT During pneumonic plague, the bacterium Yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. This lesion development and persistence are poorly understood. Here, we examine spatially distinct regions of lung lesions using laser capture microdissection and transcriptome sequencing (RNA-seq) analysis to identify transcriptional differences between lesion microenvironments. We show that cellular pathways involved in leukocyte migration and apoptosis are downregulated in the center of lung lesions compared to the periphery. Probing for the bacterial factor(s) important for the alteration in neutrophil survival, we show both in vitro and in vivo that Y. pestis increases neutrophil survival in a manner that is dependent on the type III secretion system effector YopM. This research explores the complexity of spatially distinct host-microbe interactions and emphasizes the importance of cell relevance in assays in order to fully understand Y. pestis virulence. PMID:26463167

  19. Primary pneumonic plague in the African Green monkey as a model for treatment efficacy evaluation

    PubMed Central

    Layton, R. Colby; Brasel, Trevor; Gigliotti, Andrew; Barr, Edward; Storch, Steven; Myers, Leslie; Hobbs, Charles; Koster, Frederick

    2010-01-01

    Background Primary pneumonic plague is rare among humans but treatment efficacy may be tested in appropriate animal models under the FDA ‘Animal Rule’. Methods Ten African Green monkeys (AGM) inhaled 44 to 255 LD50 doses of aerosolized Y. pestis strain CO92. Continuous telemetry, arterial blood gases, chest radiography, blood culture, and clinical pathology monitored disease progression. Results Onset of fever, >39°C detected by continuous telemetry, 52 to 80 h post-exposure Was the first sign of systemic disease and provides a distinct signal for treatment initiation. Secondary endpoints of disease severity include tachypnea, measured by telemetry, bacteremia, extent of pneumonia imaged by chest x-ray, and serum lactate dehydrogenase enzyme levels. Conclusions Inhaled Y. pestis in the AGM results in a rapidly progressive and uniformly fatal disease with fever and multifocal pneumonia, serving as a rigorous test model for antibiotic efficacy studies. PMID:20722770

  20. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

    SciTech Connect

    Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori; Tsuneyama, Koichi; Endo, Shinya; Tsukui, Tohru; Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

    2012-10-01

    Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

  1. Circumventing Y. pestis Virulence by Early Recruitment of Neutrophils to the Lungs during Pneumonic Plague

    PubMed Central

    Vagima, Yaron; Zauberman, Ayelet; Levy, Yinon; Gur, David; Tidhar, Avital; Aftalion, Moshe; Shafferman, Avigdor; Mamroud, Emanuelle

    2015-01-01

    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 development of novel

  2. Pneumonitis in bone marrow transplant recipients results from a local immune response.

    PubMed Central

    Milburn, H J; Du Bois, R M; Prentice, H G; Poulter, L W

    1990-01-01

    Eighteen recipients of allogeneic T cell-depleted bone marrow who developed 22 episodes of interstitial pneumonitis were investigated by bronchoalveolar lavage for the cause of pneumonitis. The cells obtained were examined using a panel of monoclonal antibodies with immunocytochemical techniques to identify lymphocyte subsets and the presence of surface molecules indicative of lymphocyte activation. The majority of patients had an excess of lymphocytes in lavage and most of these cells were positively stained with the McAb recognizing the CD8 antigen (suppressor/cytotoxic type T cells). Although the proportions of CD4+ (helper type) T cells were below normal, the absolute numbers were within normal limits, thus the CD4:CD8 ratio was consistently 1:1 or less. A large proportion of the CD8+ cells displayed HLA-DR molecules (RFDR1+), interleukin-2 (IL-2) receptors (CD25+) and high concentration of CD7 antigen (RFT2+). Further analysis revealed that most CD8+ cells were CD5+ (RFT1+) yet a large proportion (20-40%) were CD5-. A majority of CD8+ cells was also CD38+ (RFT10+) and Leu7+. No clear correlation between the emergence of a raised proportion of activated CD8+ cells and diagnosed cytomegalovirus infection was found. These results demonstrate, however, that cells with the phenotype of the resident T cells of the bronchial epithelium (CD8+CD5-) emerge to the air spaces and express activation markers. This raises the intriguing paradox of an aggressive local immune response occurring in an otherwise immunosuppressed group of patients. PMID:2201468

  3. European Chemicals Agency dossier submissions as an experimental data source: refinement of a fish toxicity model for predicting acute LC50 values.

    PubMed

    Austin, Thomas; Denoyelle, Marieva; Chaudry, Amjad; Stradling, Sam; Eadsforth, Charles

    2015-02-01

    As a result of the stringent data requirements of the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) regulation, a vast amount of ecotoxicological data has become available through the dissemination portal of the European Chemicals Agency (ECHA). As of April 2014, the database contained 12,439 unique substances from 47,909 dossiers. This vast database could be used to refine existing, or to create new, non-testing methods, such as quantitative structure-activity relationships (QSARs). Acute fish toxicity data were mined from the ECHA database using the eChemPortal; after filtering for single organic substances, 1159 experimental data points remained, representing 564 compounds. To evaluate the quality and accessibility of this data, the authors used the data to refine and improve an existing QSAR. The reliability of the data submitted to the ECHA database, as well as the effectiveness of the Klimisch scoring system, were assessed by comparing the refined QSAR with established QSAR benchmarks. The model developed meets all Organisation for Economic Co-operation and Development principles, has strong internal (leave-one-out internally cross-validated correlation coefficient [Q(2)(LOO)] = 0.91) and external (external coefficient of determination (predicted vs experimental [test set])) validation statistics, and can provide reliable fish median lethal concentration (LC50) predictions for non-polar narcotics. Although some issues with dossier misinformation were discovered, it was found that the ECHA dissemination portal is a valuable and reliable data source. When queried using the eChemPortal, chemical dossiers containing reliable data could be found quickly. The ECHA dissemination portal holds great potential for future QSAR development and improvement, such as updating QSARs within the Ecological Structure-Activity Relationships (ECOSAR) program. PMID:25470737

  4. Down-regulation of cytochrome P450 2C family members and positive acute-phase response gene expression by peroxisome proliferator chemicals.

    PubMed

    Corton, J C; Fan, L Q; Brown, S; Anderson, S P; Bocos, C; Cattley, R C; Mode, A; Gustafsson, J A

    1998-09-01

    In this study, we show that peroxisome proliferator chemical (PPC) exposure leads to alterations in the expression of genes in rat liver regulated by the sex-specific growth hormone secretory pattern and induced during inflammation. Expression of the male-specific cytochrome P450 (P450) 2C11 and alpha2 urinary globulin (alpha2u) genes and the female-specific P450 2C12 gene was down-regulated by some PPC. Expression of P450 2C13, also under control by the sex-specific growth hormone secretory pattern, was not altered by PPC treatment, indicating that regulation of CYP2C family members does not involve perturbation of the growth hormone secretory pattern. In contrast to the increases in expression observed when inflammation was induced in male rats, two positive acute-phase response genes, alpha1-acid glycoprotein and beta-fibrinogen, were decreased by PPC exposure. The down-regulation of the P450 2C11 by WY-14,643 could be reproduced in cultured rat hepatocytes, indicating the down-regulation is a direct effect. Experiments in wild-type mice and mice that lacked a functional peroxisome proliferator-activated receptor-alpha gene showed that down-regulation by WY of alpha1-acid glycoprotein, beta-fibrinogen, and a mouse homologue of alpha2u was dependent on peroxisome proliferator-activated receptor-alpha expression. Our results demonstrate that PPC exposure leads to down-regulation of diverse liver-specific genes, including CYP2C family members important in hormonal homeostasis and acute-phase response genes important in inflammatory responses. PMID:9730905

  5. Drug-Related Pneumonitis During Mammalian Target of Rapamycin Inhibitor Therapy: Radiographic Pattern-Based Approach in Waldenström Macroglobulinemia as a Paradigm

    PubMed Central

    Boswell, Erica N.; Hatabu, Hiroto; Ghobrial, Irene M.; Ramaiya, Nikhil H.

    2015-01-01

    Background. This study determined the frequency of drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy in Waldenström macroglobulinemia patients and investigated the imaging characteristics and radiographic patterns of pneumonitis. Materials and Methods. A total of 40 patients (23 men, 17 women; 43–84 years old) with Waldenström macroglobulinemia treated in 2 trials of the mTOR inhibitor everolimus were retrospectively studied. Chest computed tomography (CT) scans during therapy were reviewed for abnormalities suspicious for drug-related pneumonitis by the consensus of three radiologists, evaluating the extent, distributions, and specific findings. The radiographic patterns of pneumonitis were classified using the American Thoracic Society/European Respiratory Society classification of interstitial pneumonia. Results. Drug-related pneumonitis was noted in 23 patients (58%). The median time from the initiation of therapy to the onset of pneumonitis was 5.7 months. Lower lungs were involved in all 23 patients, with a higher extent than in the other zones (p < .001). The distribution was peripheral and lower in 11 patients (48%) and mixed and multifocal in 10 (44%). The findings were bilateral in 20 patients (87%). Ground glass opacities (GGOs) and reticular opacities were present in all 23 patients, with consolidation in 12, traction bronchiectasis in 2, and centrilobular nodularity in 1. The pattern of pneumonitis was classified as cryptogenic organizing pneumonia (COP) in 16 (70%) and nonspecific interstitial pneumonia (NSIP) in 7 (30%), with overlapping features of COP and NSIP in 7 patients. Conclusion. Drug-related pneumonitis was noted on CT in 58% of Waldenström macroglobulinemia patients treated with mTOR inhibitor therapy. Most common findings were bilateral GGOs and reticular opacities, with or without consolidation, in peripheral and lower lungs, demonstrating COP and NSIP patterns. Implications for Practice: The

  6. Investigation of the Relationship Between Gross Tumor Volume Location and Pneumonitis Rates Using a Large Clinical Database of Non-Small-Cell Lung Cancer Patients

    SciTech Connect

    Vinogradskiy, Yevgeniy; Tucker, Susan L.; Liao Zhongxing; Martel, Mary K.

    2012-04-01

    Purpose: Studies have suggested that function may vary throughout the lung, and that patients who have tumors located in the base of the lung are more susceptible to radiation pneumonitis. The purpose of our study was to investigate the relationship between gross tumor volume (GTV) location and pneumonitis rates using a large clinical database of 547 patients with non-small-cell lung cancer. Methods and Materials: The GTV centroids of all patients were mapped onto one common coordinate system, in which the boundaries of the coordinate system were defined by the extreme points of each individual patient lung. The data were qualitatively analyzed by graphing all centroids and displaying the data according to the presence of severe pneumonitis, tumor stage, and smoking status. The centroids were grouped according to superior-inferior segments, and the pneumonitis rates were analyzed. In addition, we incorporated the GTV centroid information into a Lyman-Kutcher-Burman normal tissue complication probability model and tested whether adding spatial information significantly improved the fit of the model. Results: Of the 547 patients analyzed, 111 (20.3%) experienced severe radiation pneumonitis. The pneumonitis incidence rates were 16%, 23%, and 21% for the superior, middle, and inferior thirds of the lung, respectively. Qualitatively, the GTV centroids of nonsmokers were notably absent from the superior portion of the lung. In addition, the GTV centroids of patients who had Stage III and IV clinical staging were concentrated toward the medial edge of the lung. The comparison between the GTV centroid model and the conventional dose-volume model did not yield a statistically significant difference in model fit. Conclusions: Lower pneumonitis rates were noted for the superior portion of the lung; however the differences were not statistically significant. For our patient cohort, incorporating GTV centroid information did not lead to a statistically significant improvement

  7. From cellular to chemical approach for acute neural and alternative options for age-induced functional diseases

    PubMed Central

    Bukovsky, Antonin

    2015-01-01

    Endogenous “stem cell niche” (SCN) accompanying vessels contains immune system components which in vivo determine differentiation of multi potent stem cells toward proper cell types in given tissue. Combinations of sex steroids may represent novel chemical approach for neuronal areas of regenerative medicine, since they cause transformation of vascular smooth muscle stem cells into differentiating neuronal cells. Circulating sex steroids are present during pregnancy and can be utilized where needed, when various embryonic/fetal tissues develop from their stem cells. Utilization of induced regeneration of tissues (regenerative medicine) is expected being more effective in sudden failures of younger individuals carrying intact SCN, as compared to established chronic disorders caused by SCN alteration. An essential component of SCN are monocyte-derived cells exhibiting tissue-specific “stop effect” (SE) preventing, for instance, an aging of neuronal cells. Its alteration causes that implantation of neuronal stem cells will also result in their differentiation toward aging cells. When we repair the SE by supply of circulating mononuclear cells from young healthy individuals, we may be able to provide novel regenerative treatments of age-induced neural diseases by sex steroid combinations. Questions regarding some age-induced body alterations are also addressed. PMID:26435770

  8. [A case of hypersensitivity pneumonitis caused by inhalation of Mycobacterium avium from a home bath with a circulating water system].

    PubMed

    Kenmotsu, Hirotsugu; Honda, Atsuro; Baba, Tomohisa; Matsumoto, Yutaka; Shichi, Izumi; Eto, Takashi; Arai, Kazumori

    2005-11-01

    A 26-year-old man presented with complaints of exertional dyspnea and cough. The patient has already been given corticosteroids at a previous hospital. Chest CT revealed small centrilobular nodules with diffuse ground-glass opacities in both lungs. Lung biopsy specimens at thoracoscopy revealed non-necrotizing granulomas, patchy foci of mononuclear cell infiltration and fibrous thickening of alveolar septa, and Masson's bodies in bronchioles. Sputum culture showed the growth of Mycobacterium avium complex (MAC). Culture of water from the bath tub of his home showed MAC. Administration of antituberculous drugs and corticosteroids, and avoidance of bathing at home resulted in the improvement of his symptoms and CT findings. We believe the case is hypersensitivity pneumonitis to MAC in an immunocompetent patient, simulating hot tub lung. Hypersensitivity pneumonitis caused by MAC is rare in Japan. PMID:16366369

  9. A tutorial for analysing the cost-effectiveness of alternative methods for assessing chemical toxicity: the case of acute oral toxicity prediction.

    PubMed

    Norlen, Hedvig; Worth, Andrew P; Gabbert, Silke

    2014-05-01

    Compared with traditional animal methods for toxicity testing, in vitro and in silico methods are widely considered to permit a more cost-effective assessment of chemicals. However, how to assess the cost-effectiveness of alternative methods has remained unclear. This paper offers a user-oriented tutorial for applying cost-effectiveness analysis (CEA) to alternative (non-animal) methods. The purpose is to illustrate how CEA facilitates the identification of the alternative method, or the combination of methods, that offers the highest information gain per unit of cost. We illustrate how information gains and costs of single methods and method combinations can be assessed. By using acute oral toxicity as an example, we apply CEA to a set of four in silico methods (ToxSuite, TOPKAT, TEST, ADMET Predictor), one in vitro method (the 3T3 Neutral Red Uptake cytotoxicity assay), and various combinations of these methods. Our results underline that in silico tools are more cost-effective than the in vitro test. Battery combinations of alternative methods, however, do not necessarily outperform single methods, because additional information gains from the battery are easily outweighed by additional costs. PMID:24901905

  10. Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and inter-laboratory testing, life stage, and species

    USGS Publications Warehouse

    Raimondo, Sandy; Lilavois, Crystal R.; Lee, Larisa; Augspurger, Tom; Wang, Ning; Ingersoll, Christopher G.; Bauer, Candice R.; Hammer, Edward J.; Barron, Mace G.

    2015-01-01

    We developed a toxicity database for unionid mussels to examine the extent of intra- and inter-laboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the two life stages; and the variation in sensitivity among commonly tested mussels (Lampsilis siliquoidea, Utterbackia imbecillis, Villosa iris), commonly tested cladocerans (Daphnia magna, Ceriodaphnia dubia) and fish (Oncorhynchus mykiss, Pimephales promelas, Lepomis macrochirus). The results of these analyses indicate intra-laboratory variability for median effect concentrations (EC50) averaged about 2 fold for both life stages, while inter-laboratory variability averaged 3.6 fold for juvenile mussels and 6.3 fold for glochidia. The EC50s for juveniles and glochidia were within a factor of 2 of each other for 50% of paired records across chemicals, with juveniles more sensitive than glochidia by more than 2 fold for 33% of the comparisons made between life stages. There was a high concurrence of the sensitivity of commonly tested L. siliquoidea, U. imbecillis, and V. iris to that of other mussels. However, this concurrence decreases as the taxonomic distance of the commonly tested cladocerans and fish to mussels increases. The compiled mussel database and determination of data variability will advance risk assessments by including more robust species sensitivity distributions, interspecies correlation estimates, and availability of taxon-specific empirically derived application factors for risk assessment.

  11. Primary case of human pneumonic plague occurring in a Himalayan marmot natural focus area Gansu Province, China.

    PubMed

    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. PMID:25555623

  12. Lymphocytic interstitial pneumonitis: a cause of pulmonary gallium-67 uptake in a child with acquired immunodeficiency syndrome

    SciTech Connect

    Zuckier, L.S.; Ongseng, F.; Goldfarb, C.R.

    1988-05-01

    Lymphocytic interstitial pneumonitis (LIP) is currently recognized as a frequent pediatric manifestation of the acquired immunodeficiency syndrome (AIDS). We report the gallium scan findings in a 3-yr-old girl with this disorder and review its clinical, radiologic, and pathologic features. LIP must be a prime consideration in the differential diagnosis of diffuse pulmonary gallium uptake in pediatric AIDS patients. Further experience will afford greater perspective on the diagnostic role that nuclear medicine will ultimately play in this disease. 49 references.

  13. Cellular Inflammatory Infiltrate in Pneumonitis Induced by a Single Moderate Dose of Thoracic X Radiation in Rats

    PubMed Central

    Szabo, Sara; Ghosh, Swarajit N.; Fish, Brian L.; Bodiga, Sreedhar; Tomic, Rade; Kumar, Gagan; Morrow, Natalya V.; Moulder, John E.; Jacobs, Elizabeth R.; Medhora, Meetha

    2010-01-01

    The goal of these studies was to characterize the infiltrating inflammatory cells during pneumonitis caused by moderate doses of radiation. Two groups of male rats (WAG/RijCmcr, 8 weeks old) were treated with single 10- or 15-Gy doses of thoracic X radiation; a third group of age-matched animals served as controls. Only 25% rats survived the 15-Gy dose. Bronchoalveolar lavage fluid and whole lung mounts were subjected to cytological and histological evaluation after 8 weeks for distribution of resident macrophages, neutrophils, lymphocytes and mast cells. There was a modest increase in airway and airspace-associated neutrophils in lungs from rats receiving 15 Gy. Mast cells (detected by immunohistochemistry for tryptase) increased over 70% with 10 Gy and over 13-fold after 15 Gy, with considerable leakage of tryptase into blood vessels and airways. Circulating levels of eight inflammatory cytokines were not altered after 10 Gy but appeared to decrease after 15 Gy. In summary, there were only modest increases in cellular inflammatory infiltrate during pneumonitis after a non-lethal dose of 10 Gy, but there was a dramatic rise in mast cell infiltration after 15 Gy, suggesting that circulating levels of mast cell products may be useful markers of severe pneumonitis. PMID:20334527

  14. Phase 2 study of idelalisib and entospletinib: pneumonitis limits combination therapy in relapsed refractory CLL and NHL

    PubMed Central

    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.

    2016-01-01

    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. PMID:26968534

  15. Phase 2 study of idelalisib and entospletinib: pneumonitis limits combination therapy in relapsed refractory CLL and NHL.

    PubMed

    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. PMID:26968534

  16. Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: Investigation of nicotinic acid receptor agonists

    SciTech Connect

    Zgoda-Pols, Joanna R.; Chowdhury, Swapan; Wirth, Mark; Milburn, Michael V.; Alexander, Danny C.; Alton, Kevin B.

    2011-08-15

    An investigative renal toxicity study using metabolomics was conducted with a potent nicotinic acid receptor (NAR) agonist, SCH 900424. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques were used to identify small molecule biomarkers of acute kidney injury (AKI) that could aid in a better mechanistic understanding of SCH 900424-induced AKI in mice. The metabolomics study revealed 3-indoxyl sulfate (3IS) as a more sensitive marker of SCH 900424-induced renal toxicity than creatinine or urea. An LC-MS assay for quantitative determination of 3IS in mouse matrices was also developed. Following treatment with SCH 900424, 3IS levels were markedly increased in murine plasma and brain, thereby potentially contributing to renal- and central nervous system (CNS)-related rapid onset of toxicities. Furthermore, significant decrease in urinary excretion of 3IS in those animals due to compromised renal function may be associated with the elevation of 3IS in plasma and brain. These data suggest that 3IS has a potential to be a marker of renal and CNS toxicities during chemically-induced AKI in mice. In addition, based on the metabolomic analysis other statistically significant plasma markers including p-cresol-sulfate and tryptophan catabolites (kynurenate, kynurenine, 3-indole-lactate) might be of toxicological importance but have not been studied in detail. This comprehensive approach that includes untargeted metabolomic and targeted bioanalytical sample analyses could be used to investigate toxicity of other compounds that pose preclinical or clinical development challenges in a pharmaceutical discovery and development. - Research Highlights: > Nicotinic acid receptor agonist, SCH 900424, caused acute kidney injury in mice. > MS-based metabolomics was conducted to identify potential small molecule markers of renal toxicity. > 3-indoxyl-sulfate was found to be as a more sensitive marker of renal toxicity than creatinine

  17. Hypersensitivity pneumonitis: lessons for diagnosis and treatment of a rare entity in children

    PubMed Central

    2013-01-01

    Hypersensitivity pneumonitis (HP) also called exogenous allergic alveolitis = extrinsic allergic alveolitis in children is an uncommon condition and may not be recognized and treated appropriately. To assess current means of diagnosis and therapy and compare this to recommendations, we used the Surveillance Unit for Rare Paediatric Disorders (ESPED) to identify incident cases of HP in Germany during 2005/6. In addition, cases of HP reported for reference from all over Germany to our center in the consecutive year were included. Twenty-three children with confirmed pediatric HP were identified. All (age 9.4 y (4.4-15.1) presented with dyspnoea at rest or with exercise, mean FVC was 39% of predicted, seven of the 23 children already had a chronic disease state at presentation. IgG against bird was elevated in 20, and against fungi in 15. Bronchoalveolar lavage was done in 18 subjects (41% lymphocytes, CD4/CD8 1.99), and lung biopsy in 6. Except 2, all children were treated with prolonged courses of systemic steroids. Outcome was not favourable in all cases. Late diagnosis in up to a quarter of the children with HP and inappropriate steroid treatment must be overcome to improve management of HP. Inclusion of children with HP into international, web-based registry studies will help to study and follow up such rare lung diseases. PMID:23924322

  18. [A case of interstitial pneumonia exacerbated by kampo-induced pneumonitis].

    PubMed

    Suzuki, Kazuo; Kinebuchi, Shinichi; Sugiyama, Kentaro; Satoh, Hiroshi; Tango, Masuo; Moriyama, Hirochi; Terada, Masaki; Ooi, Hidemi; Hasegawa, Takashi; Igarashi, Kenichi; Satoh, Makoto; Suzuki, Eiichi; Gejyo, Fumitake

    2002-07-01

    A 65-year-old woman who had complained of non-productive cough since May 1998 visited our hospital on November 5, 2000. She had been treated at another hospital with Kampo (Chinese herbal medicine), including Moku-boui-to, Bakumon-do-to, and Saiko-keishi-kankyo-to for chronic non-productive cough. Chest radiographs and CT films showed the reticular shadows that had been present in 1998, in both lower lung fields, and also demonstrated new reticular shadows in the right upper lung field and left lingular segment. Laboratory data revealed hypoxemia and pulmonary function tests revealed restrictive ventilatory disturbance, so she was admitted to our hospital on November 9, 2000. After the cessation of Kampo treatment, her symptoms disappeared, and the hypoxemia, restrictive disturbance, and reticular shadows in the chest radiograph gradually improved. Video-assisted lung biopsy specimens showed thickened alveolar walls with lymphocyte and eosinophil infiltration. A leukocyte migration test was positive for Moku-boui-to, Bakumon-do-to, and weakly positive for Saiko-keishi-kankyo-to. Although no challenge test for Kampo was performed, we diagnosed this case as interstitial pneumonia exacerbated Kampo-induced pneumonitis based on these clinical, laboratory and histological findings. PMID:12382427

  19. Hypersensitivity pneumonitis associated with azathioprine therapy in a patient with granulomatosis with polyangiitis.

    PubMed

    Lee, In Hee; Kang, Gun Woo; Kim, Kyung Chan

    2016-07-01

    Granulomatosis with polyangiitis (GPA), an autoimmune disease characterized by inflammatory granulomas and necrotizing small-vessel vasculitis, primarily affects the respiratory tract and kidneys. Azathioprine (AZA) is a purine analog that is commonly used for maintaining GPA remission after induction therapy with cyclophosphamide. While the dose-dependent side effects of AZA are common and well known, hypersensitivity reactions such as pulmonary toxicity are rare. Here, we describe a case involving a 38-year-old man with GPA-associated pauci-immune crescentic glomerulonephritis who developed subacute hypersensitivity pneumonitis (HP) during AZA maintenance therapy. Five months after the initiation of AZA administration (100 mg/day), the patient was admitted with a 7-day history of cough, dyspnea, and fever. High-resolution computed tomography of the chest showed ill-defined centrilobular nodules and diffuse ground-glass opacities in both lung fields. Bronchoscopy with bronchoalveolar lavage was negative for infectious etiologies. A transbronchial lung biopsy specimen revealed poorly formed non-necrotizing granulomas. A chest radiograph obtained at 2 weeks after discontinuation of AZA showed normal findings. The findings from this case suggest that AZA-induced HP should be considered as a differential diagnosis when a patient with GPA exhibits fresh pulmonary lesions accompanied by respiratory symptoms during AZA therapy. PMID:27155976

  20. The value of family history in the diagnosis of hypersensitivity pneumonitis in children*

    PubMed Central

    Cardoso, Joana; Carvalho, Isabel

    2014-01-01

    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. PMID:24831404

  1. Clinical features, outcomes and treatment-related pneumonitis in elderly patients with esophageal carcinoma

    PubMed Central

    He, Jian; Zeng, Zhao-Chong; Shi, Shi-Ming; Yang, Ping

    2014-01-01

    AIM: To investigate the clinical features and prognoses of elderly patients with esophageal carcinoma and to compare the effects of radiotherapy and rates of treatment-related pneumonitis (TRP) between elderly and non-elderly patients. METHODS: A total of 236 patients with esophageal carcinoma who received radiotherapy between 2002 and 2012 were enrolled. The patients were divided into two groups: an elderly group (age ≥ 65 years) and a non-elderly group (age < 65 years). The tumor position and stage, lymph node and distant metastases, and incidence and severity of TRP were compared. Multivariate analysis was applied to identify independent prognostic factors. RESULTS: The median overall survival times after radiotherapy in the elderly and non-elderly groups were 18.5 and 20.5 mo, respectively. Cox regression analysis showed that TRP grade and tumor-node-metastasis (TNM) stage were independent prognostic factors in the elderly group. High-dose radiotherapy (> 60 Gy) was associated with a high incidence of TRP. Tumor TNM staging was significantly different between the two groups in which TRP occurred. Multivariate analysis showed that TNM stage was an independent prognostic factor. Esophageal carcinoma in elderly patients was relatively less malignant compared with that in non-elderly patients. CONCLUSION: An appropriate dose should be used to decrease the incidence of TRP in radiotherapy, and intensity modulated radiation therapy should be selected if possible. PMID:25278715

  2. Immune complexes, gallium lung scans, and bronchoalveolar lavage in idiopathic interstitial pneumonitis-fibrosis

    SciTech Connect

    Gelb, A.F.; Dreisen, R.B.; Epstein, J.D.; Silverthorne, J.D.; Bickel, Y.; Fields, M.; Border, W.A.; Taylor, C.R.

    1983-08-01

    We obtained results of lung immune complexes (LIC), circulating immune complexes (CIC), 48-hour gallium lung scans (scans), bronchoalveolar lavage (BAL), and pulmonary function tests in 20 patients with idiopathic interstitial pneumonitis-fibrosis. Sixteen patients had predominantly interstitial (13 cases UIP) and/or intraalveolar (3 cases DIP) cellular disease (group 1). Prior to corticosteroid therapy in group 1, scans were positive in 75 percent, CIC were elevated in 86 percent, LIC were present in 64 percent, and BAL was abnormal in 90 percent. Duration of follow-up after treatment was 3.5 +/- 1.0 year. In group 1 after treatment with corticosteroids in 13 patients and corticosteroids and penicillamine (three patients) and plasmapheresis (one patient), only four patients remain stable or improved. After corticosteroid therapy, elevated CIC returned to normal values despite progressive patient deterioration. In three patients, lung immune complexes were still detected after circulating immune complexes had returned to normal after corticosteroid therapy. In group 2 were four patients with fibrotic disease; scans and CIC were uniformly negative, LIC were weakly present in only one patient, and BAL was abnormal in all. Despite corticosteroid therapy, all have died or deteriorated. These results suggest that positive gallium lung scans, BAL, circulating immune complexes, and to a lesser extent, lung immune complexes are associated with the cellular phase of interstitial pneumonia, but do not reliably identify a corticosteroid-responsive group.

  3. Acute Bronchitis

    MedlinePlus

    ... or though physical contact (for example, on unwashed hands). Being exposed to tobacco smoke, air pollution, dusts, vapors, and fumes can also cause acute bronchitis. Less often, bacteria can also cause acute bronchitis. To diagnose acute ...

  4. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... control. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  5. Short-Term Treatment with a SOD/Catalase Mimetic, EUK-207, Mitigates Pneumonitis and Fibrosis after Single-Dose Total-Body or Whole-Thoracic Irradiation

    PubMed Central

    Gao, Feng; Fish, Brian L.; Szabo, Aniko; Doctrow, Susan R.; Kma, Lakhan; Molthen, Robert C.; Moulder, John E.; Jacobs, Elizabeth R.; Medhora, Meetha

    2013-01-01

    In the event of a radiological accident or terrorist attack, whole- or partial-body exposure can injure the lungs. To simulate such an incident, we used a single fraction of total-body irradiation (TBI) or whole-thoracic irradiation to induce pneumonitis or pulmonary fibrosis, respectively, in a rat model. The superoxide dismutase and catalase mimetic EUK-207 was given by subcutaneous injection (20 mg/kg/day, 5 days per week, once daily) starting at 7 days after irradiation and stopping before pneumonitis developed. After TBI, morbidity and the increase in breathing rates associated with pneumonitis were significantly improved in rats treated with EUK-207 compared to rats receiving irradiation alone. At 42 days after TBI (the peak of pneumonitis) changes in vascular end points including pulmonary hemodynamics ex vivo and relative arterial density in lungs were also mitigated by EUK-207. At 7 months after whole-thoracic irradiation, EUK-207 reduced synthesis of collagen as assessed by the Sircol collagen assay and Masson’s trichrome staining. Our results demonstrate promise for EUK-207 as a mitigator of radiation pneumonitis and fibrosis. We also demonstrate for the first time mitigation of multiple vascular injuries in the irradiated lung in vivo by EUK-207. PMID:23020094

  6. Characterization of a Cynomolgus Macaque Model of Pneumonic Plague for Evaluation of Vaccine Efficacy

    PubMed Central

    Price, Jessica; Martin, Shannon; Metcalfe, Karen; Krile, Robert; Barnewall, Roy; Hart, Mary Kate; Lockman, Hank

    2015-01-01

    The efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus macaques (CMs) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of Yersinia pestis strain Colorado 92. CMs were vaccinated with a range of rF1V doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. The humoral immune response following vaccination was evaluated with anti-rF1, anti-rV, and anti-rF1V bridge enzyme-linked immunosorbent assays (ELISAs). Animals were challenged via aerosol exposure on day 149. Vaccine doses and antibody responses were each significantly associated with the probability of CM survival (P < 0.0001). Vaccination also decreased signs of pneumonic plague in a dose-dependent manner. There were statistically significant correlations between the vaccine dose and the time to onset of fever (P < 0.0001), the time from onset of fever to death (P < 0.0001), the time to onset of elevated respiratory rate (P = 0.0003), and the time to onset of decreased activity (P = 0.0251) postinfection in animals exhibiting these clinical signs. Delays in the onset of these clinical signs of disease were associated with larger doses of rF1V. Immunization with ≥12 μg of rF1V resulted in 100% CM survival. Since both the vaccine dose and anti-rF1V antibody titers correlate with survival, rF1V bridge ELISA titers can be used as a correlate of protection. PMID:26224691

  7. Temporal Progression of Pneumonic Plague in Blood of Nonhuman Primate: A Transcriptomic Analysis

    PubMed Central

    Borschel, Richard; Gautam, Aarti; Miller, Stacy-Ann; Chakraborty, Nabarun; Jett, Marti

    2016-01-01

    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. PMID:27003632

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

    SciTech Connect

    Wang, Yu-Shan; Chang, Heng-Jui; Chang, Yue-Cune; Huang, Su-Chen; Ko, Hui-Ling; Chang, Chih-Chia; Yeh, Yu-Wung; Jiang, Jiunn-Song; Lee, Cheng-Yen; Chi, Mau-Shin; Chi, Kwan-Hwa

    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. INCORPORATING SINGLE NUCLEOTIDE POLYMORPHISMS INTO THE LYMAN MODEL TO IMPROVE PREDICTION OF RADIATION PNEUMONITIS

    PubMed Central

    Tucker, Susan L.; Li, Minghuan; Xu, Ting; Gomez, Daniel; Yuan, Xianglin; Yu, Jinming; Liu, Zhensheng; Yin, Ming; Guan, Xiaoxiang; Wang, Li-E; Wei, Qingyi; Mohan, Radhe; Vinogradskiy, Yevgeniy; Martel, Mary; Liao, Zhongxing

    2012-01-01

    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, TGFβ, TNFα, TNFR, MTHFR, MTRR, and VEGF) were genotyped in 141 NSCLC patients treated with definitive radiotherapy, 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 (MV) 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 TGFβ, VEGF, TNFα, XRCC1 and APEX1. With smoking status included in the MV model, the SNPs significantly associated with increased risk of RP were in genes for TGFβ, 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 versus <10% risk of RP when exposed to high MLDs. PMID:22541966

  10. Radiation Pneumonitis After Hypofractionated Radiotherapy: Evaluation of the LQ(L) Model and Different Dose Parameters

    SciTech Connect

    Borst, Gerben R.; Ishikawa, Masayori; Nijkamp, Jasper

    2010-08-01

    Purpose: To evaluate the linear quadratic (LQ) model for hypofractionated radiotherapy within the context of predicting radiation pneumonitis (RP) and to investigate the effect if a linear (L) model in the high region (LQL model) is used. Methods and Materials: The radiation doses used for 128 patients treated with hypofractionated radiotherapy were converted to the equivalent doses given in fractions of 2 Gy for a range of {alpha}/{beta} ratios (1 Gy to infinity) according to the LQ(L) model. For the LQL model, different cut-off values between the LQ model and the linear component were used. The Lyman model parameters were fitted to the events of RP grade 2 or higher to derive the normal tissue complication probability (NTCP). The lung dose was calculated as the mean lung dose and the percentage of lung volume (V) receiving doses higher than a threshold dose of xGy (V{sub x}). Results: The best NTCP fit was found if the mean lung dose, or V{sub x}, was calculated with an {alpha}/{beta} ratio of 3 Gy. The NTCP fit of other {alpha}/{beta} ratios and the LQL model were worse but within the 95% confidence interval of the NTCP fit of the LQ model with an {alpha}/{beta} ratio of 3 Gy. The V{sub 50} NTCP fit was better than the NTCP fit of lower threshold doses. Conclusions: For high fraction doses, the LQ model with an {alpha}/{beta} ratio of 3 Gy was the best method for converting the physical lung dose to predict RP.

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

    SciTech Connect

    Tucker, Susan L.; Li Minghuan; Xu Ting; Gomez, Daniel; Yuan Xianglin; Yu Jinming; Liu Zhensheng; Yin Ming; Guan Xiaoxiang; Wang Lie; Wei Qingyi; Mohan, Radhe; Vinogradskiy, Yevgeniy; Martel, Mary; Liao Zhongxing

    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.

  12. Temporal Progression of Pneumonic Plague in Blood of Nonhuman Primate: A Transcriptomic Analysis.

    PubMed

    Hammamieh, Rasha; Muhie, Seid; Borschel, Richard; Gautam, Aarti; Miller, Stacy-Ann; Chakraborty, Nabarun; Jett, Marti

    2016-01-01

    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. PMID:27003632

  13. Radiation Pneumonitis After Conventional Radiotherapy For Breast Cancer: A Prospective Study

    PubMed Central

    Isiah, Rajesh; Subhashini, J; Backianathan, Selvamani; Thangakunam, Balamugesh; Christopher, Devasagayam J

    2015-01-01

    Background Loco-regional radiotherapy is an important treatment modality in breast cancer and radiation pneumonitis (RP) is one of the early toxicities. Aim To study the occurrence, correlation of RP with patient and radiotherapy related factors and the effects on pulmonary function following conventional radiotherapy in breast cancer. Settings and Design Prospective study, from a tertiary hospital in a developing country. Materials and Methods Prospective analysis of clinical symptoms, pulmonary function and radiologic changes was done prior to and 12 weeks after adjuvant radiotherapy (n=46). Statistical analysis was done using SPSS version 10 software. Results Radiological and clinical RP was seen in 45.65% (n=21) and 19.56% (n=9) respectively. RP was significantly higher with age >50 years (OR 4.4), chest wall irradiation with electrons, (electrons 83.3% vs cobalt60 32.4%, p=0.02) and supraclavicular field treatment with 6 MV photons (p= 0.011). There was significant relationship between Inferior Lung Distance (ILD) and RP (p=0.013). The fall in Total Lung Capacity (TLC) was significantly more in those with RP (p=0.02). Conclusion Clinical RP occurs in almost one-fifth of breast cancer patients treated with conventional radiotherapy. Chest wall irradiation with electrons, supraclavicular field irradiation with 6 MV photons, higher ILD and age >50 years was associated with increased RP. The pulmonary function parameter most affected was TLC. The factors associated with increased RP should be considered when adjuvant radiotherapy is planned to minimize its likelihood and intervene appropriately. PMID:26393189

  14. ATM Polymorphisms Are Associated With Risk of Radiation-Induced Pneumonitis

    SciTech Connect

    Zhang Li; Yang Ming; Bi Nan; Fang Mingjing; Sun Tong; Ji Wei; Tan Wen; Zhao Lujun; Yu Dianke; Lin Dongxin; Wang Luhua

    2010-08-01

    Purpose: Since the ataxia telangiectasia mutated (ATM) protein plays crucial roles in repair of double-stranded DNA breaks, control of cell cycle checkpoints, and radiosensitivity, we hypothesized that variations in this gene might be associated with radiation-induced pneumonitis (RP). Methods and Materials: A total of 253 lung cancer patients receiving thoracic irradiation between 2004 and 2006 were included in this study. Common Terminology Criteria for Adverse Events version 3.0 was used to grade RP. Five haplotype-tagging single nucleotide polymorphisms (SNPs) in the ATM gene were genotyped using DNA from blood lymphocytes. Hazard ratios (HRs) and 95% confidence intervals (CIs) of RP for genotypes were computed by the Cox model, adjusted for clinical factors. The function of the ATM SNP associated with RP was examined by biochemical assays. Results: During the median 22-month follow-up, 44 (17.4%) patients developed grade {>=} 2 RP. In multivariate Cox regression models adjusted for other clinical predictors, we found two ATM variants were independently associated with increased RP risk. They were an 111G > A) polymorphism (HR, 2.49; 95% CI, 1.07-5.80) and an ATM 126713G > A polymorphism (HR, 2.47; 95% CI, 1.16-5.28). Furthermore, genotype-dependent differences in ATM expression were demonstrated both in cell lines (p < 0.001) and in individual lung tissue samples (p = 0.003), which supported the results of the association study. Conclusions: Genetic polymorphisms of ATM are significantly associated with RP risk. These variants might exert their effect through regulation of ATM expression and serve as independent biomarkers for prediction of RP in patients treated with thoracic radiotherapy.

  15. Hypersensitivity pneumonitis in nonhuman primates: studies on the relationship of immunoregulation and disease activity

    SciTech Connect

    Keller, R.H.; Calvanico, N.J.; Stevens, J.O.

    1982-01-01

    We investigated the relationship of immunoregulation to disease activity in a nonhuman primate model of pigeon breeder's disease. Two Macaca arctoides monkeys developed classical symptoms of hypersensitivity pneumonitis after sensitization and prolonged bronchial challenge, whereas 2 other monkeys remained asymptomatic after in vivo challenge. There were no differences in the percentages of T cells, B cells, monocytes, or FC..gamma..-bearing T cells between symptomatic and asymptomatic animals. Nonetheless, we found a population of concanavalin A-induced, pigeon serum- (PS) induced, and spontaneous T cells that functioned as suppressor cells in autologous in vitro co-cultures in asymptomatic animals that were missing or nonfunctional in symptomatic animals. Monocyte suppressors functioned in both groups. We used low-dose total body irradiation (TBI) to inactivate T suppressor cells. Fifteen radiation units of TBI caused no change in the physical activity, routine chemistries, or blood counts of the 4 animals. After TBI, however, the previously asymptomatic animals developed fever, tachypnea, and signs of pulmonary congestion after in vivo challenge with PS. There was no change in the response to challenge in the symptomatic group. This altered response to in vivo challenge in the previously asymptomatic group persisted for 2 wk after TBI. During this period the difference in in vitro immunoregulatory activity between Con A-induced, PS-induced, and spontaneous T cells in symptomatic and asymptomatic animals disappeared. Monocyte suppressors, however, continued to function in both groups after TBI. these data suggest that the monkey is an appropriate model for studies of human HP and that T cell immunoregulation may be an important element in the pathogenesis and disease activity of HP.

  16. Enhanced reactive oxygen species metabolism of air space cells in hypersensitivity pneumonitis

    SciTech Connect

    Calhoun, W.J. )

    1991-06-01

    Reactive oxygen species (ROS) are produced by phagocytic cells as part of host defense mechanisms, but these same products released by air space cells have been shown to contribute to pulmonary inflammation in interstitial lung diseases and likely represent a general mechanism of lung injury. However, the possible contribution of these compounds to lung inflammation in hypersensitivity pneumonitis (HP) has yet to be reported. We performed 11 bronchoalveolar lavage (BAL) studies in six patients with HP and compared the results with results from studies in 21 healthy normal volunteers. In patients with HP, spontaneous and stimulated measures of ROS metabolism by air space cells were significantly higher than those seen in normal volunteers. When alveolar macrophages were purified by depleting neutrophils and eosinophils on density gradients of Percoll (specific gravity 1.075 gm/ml), ROS metabolism remained elevated when compared with that in cells obtained from healthy controls, confirming that alveolar macrophage ROS metabolism is enhanced in patients with HP. Further, we found significant elevations in BAL total protein, lymphocytes, eosinophils, and neutrophils in patients with HP when they were compared with normal volunteers, with an increased proportion of BAL T lymphocytes expressing CD8 and natural killer surface antigens, consistent with previous work. Lavage samples from patients with HP with clinically active disease had higher proportions of BAL eosinophils and concentrations of total protein, lower forced expiratory volume in 1 second, lower forced vital capacity, and lower arterial oxygen tensions, and higher indices of ROS metabolism than samples from patients with HP with inactive disease. HP is associated with evidence of air space inflammation, to which alveolar macrophage-derived ROS may contribute.

  17. Cryptogenic organizing pneumonitis during oxaliplatin chemotherapy for colorectal cancer: case report.

    PubMed

    Garrido, Marcelo; O'Brien, Andrés; González, Sergio; Clavero, José Miguel; Orellana, Eric

    2007-12-01

    The patient presented here is a 30-year-old woman who underwent anterior resection for the initial treatment of rectal cancer. A postoperative study showed a single liver metastasis. The patient received adjuvant pelvic radiotherapy with concomitant 5-fluorouracil (5-FU) treatment followed by liver metastasectomy 6 weeks after the completion of radiation therapy and chemotherapy. Adjuvant therapy with 5-FU, leucovorin, and oxaliplatin (FOLFOX 4 regimen) was continued. The initial five cycles were well tolerated with the occurrence of only paresthesia that did not interfere with function. After the sixth cycle of the treatment, progressive dyspnea and persistent cough developed in the patient, although her clinical history was negative for lung disease. A chest radiograph revealed diffuse bilateral interstitial infiltrates, and a chest CT scan showed bilateral alveolar infiltrates predominant in the right lung. Lung biopsy by video-assisted thoracoscopy was performed, and the histologic report showed cryptogenic organizing pneumonitis (COP). Prednisone therapy (1 mg/kg/d) resulted in a very good clinical response. In fact, the patient had complete remission of respiratory symptoms including cough and dyspnea after 4 days of treatment, and the chest CT scan showed complete resolution of lung infiltrates after 4 weeks. One month later, the patient continued adjuvant treatment with six cycles of 5-FU, leucovorin, and irinotecan (ie, the FOLFIRI regimen) without complications. Thus, oxiplatin was implicated as the likely cause of this drug-induced lung toxicity, which is a very rare complication associated with platins. Diffuse interstitial lung disease, particularly COP, has been described following the administration of the cytotoxic agents bleomycin and busulfan, but a connection to oxaliplatin has not been reported before this case. PMID:18079234

  18. Immunoglobulin G Subisotype Responses of Pneumonic and Healthy, Exposed Foals and Adult Horses to Rhodococcus equi Virulence-Associated Proteins

    PubMed Central

    Hooper-McGrevy, Kathleen E.; Wilkie, Bruce N.; Prescott, John F.

    2003-01-01

    Rhodococcus equi causes severe pyogranulomatous pneumonia in foals and in immunocompromised humans. Replication of virulent isolates within macrophages correlates with the presence of a large plasmid which encodes a family of seven virulence-associated proteins (VapA and VapC to VapH), whose functions are unknown. Although cell-mediated immunity is thought to be crucial in eliminating R. equi infection, antibody partially protects foals. The antibody response to both VapA and VapC was similar in six adult horses and six naturally exposed but healthy foals, as well as in eight foals with R. equi pneumonia. The immunoglobulin G (IgG) subisotype response of pneumonic foals to Vap proteins was significantly IgGb biased and also had a trend toward higher IgGT association compared to the isotype association of antibody in adult horses and healthy exposed foals. This suggests that in horses, IgGb and IgGT are Th2 isotypes and IgGa is a Th1 isotype. Furthermore, it suggests that foals which develop R. equi pneumonia have a Th2-biased, ineffective immune response whereas foals which become immune develop a Th1-biased immune response. Pneumonic foals had significantly more antibody to VapD and VapE than did healthy exposed foals. This may indicate a difference in the expression of these two Vap proteins during persistent infection. Alternatively, in pneumonic foals the deviation of the immune response toward VapD and VapE may reflect a bias unfavorable to R. equi resistance. These data indicate possible age-related differences in the equine immune response affecting Th1-Th2 bias as well as antibody specificity bias, which together favor the susceptibility of foals to R. equi pneumonia. PMID:12738629

  19. Immunoglobulin G subisotype responses of pneumonic and healthy, exposed foals and adult horses to Rhodococcus equi virulence-associated proteins.

    PubMed

    Hooper-McGrevy, Kathleen E; Wilkie, Bruce N; Prescott, John F

    2003-05-01

    Rhodococcus equi causes severe pyogranulomatous pneumonia in foals and in immunocompromised humans. Replication of virulent isolates within macrophages correlates with the presence of a large plasmid which encodes a family of seven virulence-associated proteins (VapA and VapC to VapH), whose functions are unknown. Although cell-mediated immunity is thought to be crucial in eliminating R. equi infection, antibody partially protects foals. The antibody response to both VapA and VapC was similar in six adult horses and six naturally exposed but healthy foals, as well as in eight foals with R. equi pneumonia. The immunoglobulin G (IgG) subisotype response of pneumonic foals to Vap proteins was significantly IgGb biased and also had a trend toward higher IgGT association compared to the isotype association of antibody in adult horses and healthy exposed foals. This suggests that in horses, IgGb and IgGT are Th2 isotypes and IgGa is a Th1 isotype. Furthermore, it suggests that foals which develop R. equi pneumonia have a Th2-biased, ineffective immune response whereas foals which become immune develop a Th1-biased immune response. Pneumonic foals had significantly more antibody to VapD and VapE than did healthy exposed foals. This may indicate a difference in the expression of these two Vap proteins during persistent infection. Alternatively, in pneumonic foals the deviation of the immune response toward VapD and VapE may reflect a bias unfavorable to R. equi resistance. These data indicate possible age-related differences in the equine immune response affecting Th1-Th2 bias as well as antibody specificity bias, which together favor the susceptibility of foals to R. equi pneumonia. PMID:12738629

  20. Thin-Section CT Characteristics and Longitudinal CT Follow-up of Chemotherapy Induced Interstitial Pneumonitis: A Retrospective Cohort Study.

    PubMed

    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 < 0.001, respectively). In comparison with Group 1 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 < 0.001). Use of a CT pattern-recognition approach to CIIP is appropriate and practical in interpreting radiological findings. PMID:26765442

  1. Predicting Lung Radiotherapy-Induced Pneumonitis Using a Model Combining Parametric Lyman Probit With Nonparametric Decision Trees

    SciTech Connect

    Das, Shiva K. . E-mail: shiva.das@duke.edu; Zhou Sumin; Zhang, Junan; Yin, F.-F.; Dewhirst, Mark W.; Marks, Lawrence B.

    2007-07-15

    Purpose: To develop and test a model to predict for lung radiation-induced Grade 2+ pneumonitis. Methods and Materials: The model was built from a database of 234 lung cancer patients treated with radiotherapy (RT), of whom 43 were diagnosed with pneumonitis. The model augmented the predictive capability of the parametric dose-based Lyman normal tissue complication probability (LNTCP) metric by combining it with weighted nonparametric decision trees that use dose and nondose inputs. The decision trees were sequentially added to the model using a 'boosting' process that enhances the accuracy of prediction. The model's predictive capability was estimated by 10-fold cross-validation. To facilitate dissemination, the cross-validation result was used to extract a simplified approximation to the complicated model architecture created by boosting. Application of the simplified model is demonstrated in two example cases. Results: The area under the model receiver operating characteristics curve for cross-validation was 0.72, a significant improvement over the LNTCP area of 0.63 (p = 0.005). The simplified model used the following variables to output a measure of injury: LNTCP, gender, histologic type, chemotherapy schedule, and treatment schedule. For a given patient RT plan, injury prediction was highest for the combination of pre-RT chemotherapy, once-daily treatment, female gender and lowest for the combination of no pre-RT chemotherapy and nonsquamous cell histologic type. Application of the simplified model to the example cases revealed that injury prediction for a given treatment plan can range from very low to very high, depending on the settings of the nondose variables. Conclusions: Radiation pneumonitis prediction was significantly enhanced by decision trees that added the influence of nondose factors to the LNTCP formulation.

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

    SciTech Connect

    Dobrocky, Tomas; Fuerstner, Markus Klaeser, Bernd; Lopez-Benitez, Ruben; Wälti, Yara Banz; Kara, Levent

    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.

  3. Effect of Azithromycin plus Rifampin versus Amoxicillin Alone on Eradication and Inflammation in the Chronic Course of Chlamydia pneumoniae Pneumonitis in Mice

    PubMed Central

    Bin, Xie Xiao; Wolf, Katerina; Schaffner, Thomas; Malinverni, Raffaele

    2000-01-01

    The effects of treatment with azithromycin plus rifampin (A+R), amoxicillin (A), or placebo (P) on the chronic course of experimental Chlamydia pneumoniae pneumonitis in mice were assessed by culture, PCR, and immunocytochemistry as well as by degree of inflammation in lung tissue. Eradication of the pathogen was significantly more frequent and inflammation in tissue was significantly reduced after treatment with A+R compared to after treatment with A or P. Combination therapy with azithromycin plus rifampin showed favorable effects in the chronic course of C. pneumoniae pneumonitis. PMID:10817751

  4. Challenging complications of treatment – human herpes virus 6 encephalitis and pneumonitis in a patient undergoing autologous stem cell transplantation for relapsed Hodgkin's disease: a case report

    PubMed Central

    Bommer, Martin; Pauls, Sandra; Greiner, Jochen

    2009-01-01

    Background Reactivation of human herpesvirus 6 (HHV-6) occurs frequently in patients after allogeneic stem cell transplantation and is associated with bone-marrow suppression, enteritis, pneumonitis, pericarditis and also encephalitis. After autologous stem cell transplantation or intensive polychemotherapy HHV-6 reactivation is rarely reported. Case report This case demonstrates a severe symptomatic HHV-6 infection with encephalitis and pneumonitis after autologous stem cell transplantation of a patient with relapsed Hodgkin's disease. Conclusion Careful diagnostic work up in patients with severe complications after autologous stem cell transplantation is mandatory to identify uncommon infections. PMID:19619326

  5. Resolution of Chronic Aspiration Pneumonitis Following Endoscopic Endonasal Repair of Spontaneous Cerebrospinal Fluid Fistula of the Skull Base

    PubMed Central

    Seltzer, Justin; Babadjouni, Arash; Wrobel, Bozena B.; Zada, Gabriel

    2016-01-01

    Spontaneous cerebrospinal fluid (CSF) rhinorrhea due to a skull base defect requires prompt diagnosis and treatment. Multiple surgical options are available for repairing the fistula, including the two-layer “fascial apposition” method and use of a pedicled nasal-septal flap. A 44-year-old obese woman presented with 4 months of progressive cough, exertional dyspnea, hoarseness, and intermittent fluid drainage from the right nostril. Chest computed tomography (CT) imaging and bronchoscopy showed chronic pneumonitis, which was confirmed by pulmonary wedge resection. CT and magnetic resonance imaging of the skull base, as well as laboratory analysis of the nasal fluid for β2-transferrin, confirmed a skull base defect causing CSF rhinorrhea. During surgery, insertion of a lumbar drain with the intrathecal fluorescein administration was performed, followed by endoscopic endonasal repair using an autologous fascial apposition graft and pedicled nasal-septal flap. Both the CSF leak and the pulmonary complications resolved following the operation with no symptoms at 11-month follow-up. This is the first reported case of spontaneous CSF rhinorrhea complicated by chronic aspiration and pneumonitis. Increased diagnostic complexity due to chronic pulmonary complications resulted in unnecessary interventions and treatment delays. Prompt recognition of spontaneous CSF leaks is essential to prevent potentially harmful complications. PMID:27247911

  6. [A case of severe summer-type hypersensitivity pneumonitis treated with high-dose administration of steroid].

    PubMed

    Arai, M; Kawada, H; Kaburagi, T; Sakai, N; Kudou, Y; Kawakami, M; Konno, K; Takizawa, T

    1991-11-01

    A 40-year-old man who lived in a wooden house built 30 years ago presented with complaints of fever, dry cough and dyspnea. Chest X-ray findings showed interstitial shadows throughout bilateral lung fields. After admission, high-dose administration of 3000 mg of methylprednisolone was performed because of deterioration of chest X-ray shadows and symptoms. In a week, clinical data and symptoms improved. Findings of BAL fluid on admission revealed a relative increase of lymphocytes, neutrophils and mast cells, and pathological findings of transbronchial lung biopsy revealed non-caseous granulation and alveolitis. Precipitating antibodies and indirect fluorescent antibodies against Trichosporon cutaneum and Cryptococcus neoformans had positive reactions and T. cutaneum was isolated and identified from the patient's house. A diagnosis of summer-type hypersensitivity pneumonitis was made according to the criteria advocated by Ando et al. This seemed to be a rare case of summer-type hypersensitivity pneumonitis prolonged after isolation from his normal living environment, successfully treated by high-dose administration of steroid. PMID:1770686

  7. Resolution of Chronic Aspiration Pneumonitis Following Endoscopic Endonasal Repair of Spontaneous Cerebrospinal Fluid Fistula of the Skull Base.

    PubMed

    Seltzer, Justin; Babadjouni, Arash; Wrobel, Bozena B; Zada, Gabriel

    2016-06-01

    Spontaneous cerebrospinal fluid (CSF) rhinorrhea due to a skull base defect requires prompt diagnosis and treatment. Multiple surgical options are available for repairing the fistula, including the two-layer "fascial apposition" method and use of a pedicled nasal-septal flap. A 44-year-old obese woman presented with 4 months of progressive cough, exertional dyspnea, hoarseness, and intermittent fluid drainage from the right nostril. Chest computed tomography (CT) imaging and bronchoscopy showed chronic pneumonitis, which was confirmed by pulmonary wedge resection. CT and magnetic resonance imaging of the skull base, as well as laboratory analysis of the nasal fluid for β2-transferrin, confirmed a skull base defect causing CSF rhinorrhea. During surgery, insertion of a lumbar drain with the intrathecal fluorescein administration was performed, followed by endoscopic endonasal repair using an autologous fascial apposition graft and pedicled nasal-septal flap. Both the CSF leak and the pulmonary complications resolved following the operation with no symptoms at 11-month follow-up. This is the first reported case of spontaneous CSF rhinorrhea complicated by chronic aspiration and pneumonitis. Increased diagnostic complexity due to chronic pulmonary complications resulted in unnecessary interventions and treatment delays. Prompt recognition of spontaneous CSF leaks is essential to prevent potentially harmful complications. PMID:27247911

  8. Enalapril Mitigates Radiation-Induced Pneumonitis and Pulmonary Fibrosis if Started 35 Days after Whole-Thorax Irradiation

    PubMed Central

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

    2014-01-01

    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/m2/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/m2/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. PMID:24131041

  9. U.S. EPA'S ACUTE REFERENCE EXPOSURE METHODOLOGY FOR ACUTE INHALATION EXPOSURES

    EPA Science Inventory

    The US EPA National Center for Environmental Assessment has developed a methodology to derive acute inhalation toxicity benchmarks, called acute reference exposures (AREs), for noncancer effects. The methodology provides guidance for the derivation of chemical-specific benchmark...

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

    SciTech Connect

    Lee, Sangkyu Ybarra, Norma; Jeyaseelan, Krishinima; Seuntjens, Jan; El Naqa, Issam; Faria, Sergio; Kopek, Neil; Brisebois, Pascale; Bradley, Jeffrey D.; Robinson, Clifford

    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

  11. CD34 Is Required for Dendritic Cell Trafficking and Pathology in Murine Hypersensitivity Pneumonitis

    PubMed Central

    Blanchet, Marie-Renée; Bennett, Jami L.; Gold, Matthew J.; Levantini, Elena; Tenen, Daniel G.; Girard, Melissa; Cormier, Yvon

    2011-01-01

    Rationale: Although recent work has shown that CD34 plays an important role in the trafficking of inflammatory cells during Th2-biased inflammatory responses, its role in Th1/Th17-biased disease as well as dendritic cell (DC) trafficking is unknown. Objectives: We used CD34-deficient mice (Cd34−/−) to investigate the role of CD34 in the Th1/Th17-biased lung inflammatory disease, hypersensitivity pneumonitis (HP). Methods: HP was induced in wild-type (wt) and Cd34−/− mice by repeated intranasal administration of Saccharopolyspora rectivirgula antigen. Lung inflammation was assessed by histology and analysis of bronchoalveolar lavage cells. Primary and secondary immune responses were evaluated by cytokine recall responses of pulmonary inflammatory cells as well as draining lymph node cells. Measurements and Main Results: Cd34−/− mice were highly resistant to the development of HP and exhibited an inflammatory pattern more reflective of a primary response to S. rectivirgula rather than the chronic lymphocytosis that is typical of this disease. Cytokine recall responses from Cd34−/− lymph node cells were dampened and consistent with a failure of antigen-loaded Cd34−/− DCs to deliver antigen and prime T cells in the draining lymph nodes. In agreement with this interpretation, adoptive transfer of wt DCs into Cd34−/− mice was sufficient to restore normal sensitivity to HP. CD34 was found to be expressed by wt DCs, and Cd34−/− DCs exhibited an impaired ability to chemotax toward a subset of chemokines in vitro. Finally, expression of human CD34 in Cd34−/− mice restored normal susceptibility to HP. Conclusions: We conclude that CD34 is expressed by mucosal DCs and plays an important role in their trafficking through the lung and to the lymph nodes. Our data also suggest that CD34 may play a selective role in the efficient migration of these cells to a subset of chemokines. PMID:21642249

  12. Dose response and factors related to interstitial pneumonitis after bone marrow transplant

    SciTech Connect

    Sampath, Sagus; Schultheiss, Timothy E. . E-mail: schultheiss@coh.org; Wong, Jeffrey

    2005-11-01

    Purpose: Total body irradiation (TBI) and chemotherapy are common components of conditioning regimens for bone marrow transplantation. Interstitial pneumonitis (IP) is a known regimen-related complication. Using published data of IP in a multivariate logistic regression, this study sought to identify the parameters in the bone marrow transplantation conditioning regimen that were significantly associated with IP and to establish a radiation dose-response function. Methods and Materials: A retrospective review was conducted of articles that reported IP incidence along with lung dose, fractionation, dose rate, and chemotherapy regimen. In the final analysis, 20 articles (n = 1090 patients), consisting of 26 distinct TBI/chemotherapy regimens, were included in the analysis. Multivariate logistic regression was performed to determine dosimetric and chemotherapeutic factors that influenced the incidence of IP. Results: A logistic model was generated from patients receiving daily fractions of radiation. In this model, lung dose, cyclophosphamide dose, and the addition of busulfan were significantly associated with IP. An incidence of 3%-4% with chemotherapy-only conditioning regimens is estimated from the models. The {alpha}/{beta} value of the linear-quadratic model was estimated to be 2.8 Gy. The dose eliciting a 50% incidence, D {sub 50}, for IP after 120 mg/kg of cyclophosphamide was 8.8 Gy; in the absence of chemotherapy, the estimated D {sub 50} is 10.6 Gy. No dose rate effect was observed. The use of busulfan as a substitute for radiation is equivalent to treating with 14.8 Gy in 4 fractions with 50% transmission blocks shielding the lung. The logistic regression failed to find a model that adequately fit the multiple-fraction-per-day data. Conclusions: Dose responses for both lung radiation dose and cyclophosphamide dose were identified. A conditioning regimen of 12 Gy TBI in 6 daily fractions induces an IP incidence of about 11% in the absence of lung shielding

  13. Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and inter-laboratory testing, life stage, and species - SETAC Abstract

    EPA Science Inventory

    We developed a toxicity database for unionid mussels to examine the extent of intra- and inter-laboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the two life stages; and the variation in sensitiv...

  14. Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and inter-laboratory testing, life stage, and species

    EPA Science Inventory

    The authors developed a toxicity database for unionid mussels to examine the extent of intra- and interlaboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the 2 life stages; and the variation in se...

  15. Preparation of five 3-MCPD fatty acid esters and the effects of their chemical structures on acute oral toxicity in Swiss mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty acid esters of 3-monochloro-1, 2-propanediol (3-MCPDEs), including 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters, were synthetized and examined for their acute oral toxicities in Swiss mice. 3-MCPDEs were obtained through the reaction of 3-MCPD and...

  16. Acute Bronchitis

    MedlinePlus

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis ...

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2016-08-21

    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. PMID:27461154

  19. Deletion of Braun Lipoprotein and Plasminogen-Activating Protease-Encoding Genes Attenuates Yersinia pestis in Mouse Models of Bubonic and Pneumonic Plague

    PubMed Central

    van Lier, Christina J.; Sha, Jian; Kirtley, Michelle L.; Cao, Anthony; Tiner, Bethany L.; Erova, Tatiana E.; Cong, Yingzi; Kozlova, Elena V.; Popov, Vsevolod L.; Baze, Wallace B.

    2014-01-01

    Currently, there is no FDA-approved vaccine against Yersinia pestis, the causative agent of bubonic and pneumonic plague. Since both humoral immunity and cell-mediated immunity are essential in providing the host with protection against plague, we developed a live-attenuated vaccine strain by deleting the Braun lipoprotein (lpp) and plasminogen-activating protease (pla) genes from Y. pestis CO92. The Δlpp Δpla double isogenic mutant was highly attenuated in evoking both bubonic and pneumonic plague in a mouse model. Further, animals immunized with the mutant by either the intranasal or the subcutaneous route were significantly protected from developing subsequent pneumonic plague. In mice, the mutant poorly disseminated to peripheral organs and the production of proinflammatory cytokines concurrently decreased. Histopathologically, reduced damage to the lungs and livers of mice infected with the Δlpp Δpla double mutant compared to the level of damage in wild-type (WT) CO92-challenged animals was observed. The Δlpp Δpla mutant-immunized mice elicited a humoral immune response to the WT bacterium, as well as to CO92-specific antigens. Moreover, T cells from mutant-immunized animals exhibited significantly higher proliferative responses, when stimulated ex vivo with heat-killed WT CO92 antigens, than mice immunized with the same sublethal dose of WT CO92. Likewise, T cells from the mutant-immunized mice produced more gamma interferon (IFN-γ) and interleukin-4. These animals had an increasing number of tumor necrosis factor alpha (TNF-α)-producing CD4+ and CD8+ T cells than WT CO92-infected mice. These data emphasize the role of TNF-α and IFN-γ in protecting mice against pneumonic plague. Overall, our studies provide evidence that deletion of the lpp and pla genes acts synergistically in protecting animals against pneumonic plague, and we have demonstrated an immunological basis for this protection. PMID:24686064

  20. Acute joint inflammation in mice after systemic injection of the cell wall, its peptidoglycan, and chemically defined peptidoglycan subunits from various bacteria.

    PubMed Central

    Koga, T; Kakimoto, K; Hirofuji, T; Kotani, S; Ohkuni, H; Watanabe, K; Okada, N; Okada, H; Sumiyoshi, A; Saisho, K

    1985-01-01

    The systemic injection of an aqueous suspension of cell wall or its peptidoglycan (PG)-rich sonicate derived from group A streptococcus and Lactobacillus casei induced acute joint lesions in BALB/c, DBA/1J, (BALB/c X DBA/1J)F1, and C3H/He mouse strains, but not in C57BL/6, DBA/2, and AKR strains. Cell walls and their enzymatically degraded PG fragments from other bacteria as well as the synthetic disaccharide dipeptide and Lactobacillus plantarum cell wall-derived disaccharide tripeptide produced similar acute inflammation in susceptible BALB/c mice. Acute swelling and erythema of the ankles and wrists were observed as early as 3 h, reached maximum severity by day 2, and generally subsided by days 4 to 6 after injection. Histological studies showed synovial proliferation, marked infiltration of many mononuclear cells and a few polymorphonuclear leukocytes in the soft tissues, and extensive deposition of fibrinous exudate in the joint space. Antibody response was detectable against the PG fraction. However, anti-PG antibody does not seem to be responsible for the pathogenesis of this disease. On the other hand, experiments on decomplementation by cobra venom factor suggest that complement components are involved in the early phase of this arthritic model. Images PMID:3930403

  1. Congenital rubella pneumonitis complicated by Pneumocystis jiroveci infection with positive long term respiratory outcome: a case report and literature review.

    PubMed

    Sanchez, M O; Chang, A B

    2009-12-01

    Rubella remains to be a significant illness in the developing countries because of limited access to immunizations. In congenital rubella syndrome, lung involvement becomes evident within the few months of life, as a manifestation of the "late onset rubella syndrome." The lungs and other organs become involved secondary to immunopathologic mechanisms and immunodeficiency predisposes affected patients to opportunistic pathogens. We report the clinical, respiratory and immunologic data of a young boy who developed rubella pneumonitis and concomitant infection with Pneumocystis jiroveci. Despite the complicated clinical course, the child survived. At follow-up he has a normal pulmonary examination, mild hyperinflation only on his chest radiograph, normal immunology and normal respiratory reactance and resistance. PMID:19911369

  2. Gemcitabine-Related Pneumonitis in Pancreas Adenocarcinoma—An Infrequent Event: Elucidation of Risk Factors and Management Implications

    PubMed Central

    Sahin, Ibrahim Halil; Geyer, Alexander I.; Kelly, Daniel W.; O’Reilly, Eileen Mary

    2016-01-01

    A total of 2440 pancreatic cancer patients who received gemcitabine treatment were screened for gemcitabine-related pneumonitis (GRP). The observed rate of GRP was 1.1%. History of smoking, alcohol use, and history of underlying lung disease were identified as possible risk factors of GRP. Early pulmonary consult and cessation of gemcitabine is recommended once clinical suspicion arises. Background Gemcitabine-related pneumonitis (GRP) has been reported relatively frequently for pancreas cancer in the literature; however, underlying risk factors and optimal management remain to be defined. We studied a cohort of patients with GRP and investigated potential predisposing factors in pancreatic cancer patients. Patients and Methods A total 2440 patients at Memorial Sloan Kettering Cancer Center were identified between January 1, 2000, and December 31, 2012, and were screened for grade 2 or higher GRP in an institutional tumor registry and using an ICD billing code database. Demographic and clinical information was extracted by electronic chart review. Results A total of 28 patients (1.1%) with GRP were identified. Incidence of grade 2, 3, and 4 reactions were 7 (25%), 18 (64%), and 3 (11%), respectively. No GRP-related mortality was observed. Twenty-one patients (75%) reported a history of cigarette smoking. Seventeen patients (61%) were alcohol users. Six patients (21%) were either regular or heavy drinkers. Most patients (93%) had either locally advanced or metastatic disease. Three patients (11%) underwent a diagnostic bronchoscopy, and in 1 patient a diagnosis of organizing pneumonia was established. Morbidity was significant; 3 patients (11%) required treatment in the intensive care unit. All hospitalized patients received steroid treatment. Conclusion GRP is relatively uncommon but incurs significant morbidity. Potential risk factors include advanced-stage disease, along with smoking and alcohol consumption and possibly underlying lung disease. We recommend a

  3. Establishment of a Swiss Webster Mouse Model of Pneumonic Plague To Meet Essential Data Elements under the Animal Rule

    PubMed Central

    Lin, Winston; Detrisac, Carol; Hu, Shu-Chieh; Rajendran, Narayanan; Gingras, Bruce; Holland, Louis; Price, Jessica; Bolanowski, Mark; House, Robert V.

    2012-01-01

    A recombinant vaccine (rF1V) is being developed for protection against pneumonic plague. This study was performed to address essential data elements to establish a well-characterized Swiss Webster mouse model for licensing the rF1V vaccine using the FDA's Animal Rule. These elements include the documentation of challenge material characteristics, aerosol exposure parameters, details of the onset and severity of clinical signs, pathophysiological response to disease, and relevance to human disease. Prior to animal exposures, an evaluation of the aerosol system was performed to determine and understand the variability of the aerosol exposure system. Standardized procedures for the preparation of Yersinia pestis challenge material also were developed. The 50% lethal dose (LD50) was estimated to be 1,966 CFU using Probit analysis. Following the LD50 determination, pathology was evaluated by exposing mice to a target LD99 (42,890 CFU). Mice were euthanized at 12, 24, 36, 48, 60, and 72 h postexposure. At each time point, samples were collected for clinical pathology, detection of bacteria in blood and tissues, and pathology evaluations. A general increase in incidence and severity of microscopic findings was observed in the lung, lymph nodes, spleen, and liver from 36 to 72 h postchallenge. Similarly, the incidence and severity of pneumonia increased throughout the study; however, some mice died in the absence of pneumonia, suggesting that disease progression does not require the development of pneumonia. Disease pathology in the Swiss Webster mouse is similar to that observed in humans, demonstrating the utility of this pneumonic plague model that can be used by researchers investigating plague countermeasures. PMID:22336286

  4. Inflammatory sequences in acute pulmonary radiation injury.

    PubMed Central

    Slauson, D. O.; Hahn, F. F.; Benjamin, S. A.; Chiffelle, T. L.; Jones, R. K.

    1976-01-01

    The histopathologic events in the developing acute pulmonary inflammatory reaction to inhaled particles of Yttrium 90 are detailed. In animals that died or were sacrificed during the first year after inhalation exposure, microscopic findings of acute inflammation predominated and included vascular congestion; stasis, focal hemorrhage; edema; various inflammatory cell infiltrates; cytolysis and desquamation of bronchiolar and alveolar epithelium followed by regeneration; vascular injury and repair; and the eventual development of pulmonary fibrosis. Accumulation of alveolar fibrin deposits was an additional characteristic, though not a constant feature of the early stages of radiation pneumonitis. In addition to the direct effects of radiation on pulmonary cell populations, the histopathologic findings were suggestive of diverse activation of various cellular and humoral mediation systems in their pathogenesis. The potential interrelationships of systems responsible for increased vascular permeability, coagulation and fibrinolysis, chemotaxis, and direct cellular injury were discussed and related to the pathogenesis of the microscopic findings characteristic of early pulmonary radiation injury. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:1258976

  5. Acute nephritic syndrome

    MedlinePlus

    Glomerulonephritis - acute; Acute glomerulonephritis; Nephritis syndrome - acute ... Acute nephritic syndrome is often caused by an immune response triggered by an infection or other disease. Common causes ...

  6. Simulation and optimization of pulsed radio frequency irradiation scheme for chemical exchange saturation transfer (CEST) MRI-demonstration of pH-weighted pulsed-amide proton CEST MRI in an animal model of acute cerebral ischemia.

    PubMed

    Sun, Phillip Zhe; Wang, Enfeng; Cheung, Jerry S; Zhang, Xiaoan; Benner, Thomas; Sorensen, A Gregory

    2011-10-01

    Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is capable of measuring dilute labile protons and microenvironmental properties. However, the CEST contrast is dependent upon experimental conditions-particularly, the radiofrequency (RF) irradiation scheme. Although continuous-wave RF irradiation has been used conventionally, the limited RF pulse duration or duty cycle of most clinical systems requires the use of pulsed RF irradiation. Here, the conventional numerical simulation is extended to describe pulsed-CEST MRI contrast as a function of RF pulse parameters (i.e., RF pulse duration and flip angle) and labile proton properties (i.e., exchange rate and chemical shift). For diamagnetic CEST agents undergoing slow or intermediate chemical exchange, simulation shows a linear regression relationship between the optimal mean RF power of pulsed-CEST MRI and continuous-wave-CEST MRI. The optimized pulsed-CEST contrast is approximately equal to that of continuous-wave-CEST MRI for exchange rates less than 50 s(-1), as confirmed experimentally using a multicompartment pH phantom. In the acute stroke animals, we showed that pulsed- and continuous-wave-amide proton CEST MRI demonstrated similar contrast. In summary, our study elucidated the RF irradiation dependence of pulsed-CEST MRI contrast, providing useful insights to guide its experimental optimization and quantification. PMID:21437977

  7. Simulation and optimization of pulsed radio frequency (RF) irradiation scheme for chemical exchange saturation transfer (CEST) MRI – demonstration of pH-weighted pulsed-amide proton CEST MRI in an animal model of acute cerebral ischemia

    PubMed Central

    Sun, Phillip Zhe; Wang, Enfeng; Cheung, Jerry S.; Zhang, Xiaoan; Benner, Thomas; Sorensen, A Gregory

    2011-01-01

    Chemical exchange saturation transfer (CEST) MRI is capable of measuring dilute labile protons and microenvironment properties; however, the CEST contrast is also dependent upon experimental conditions, particularly, the RF irradiation scheme. Although continuous-wave (CW) RF irradiation has been conventionally utilized, the RF pulse duration or duty cycle are limited on most clinical systems, for which pulsed RF irradiation must be chosen. Here, conventional numerical simulation was extended to describe pulsed-CEST MRI contrast as a function of RF pulse parameters (i.e., RF pulse duration and flip angle) and labile proton properties (i.e., exchange rate and chemical shift). For diamagnetic CEST agents undergoing slow/intermediate chemical exchange, our simulation showed a linear regression relationship between the optimal mean RF power for pulsed-CEST MRI and that of CW-CEST MRI. Worth noting, the optimized pulsed-CEST contrast was approximately equal to that of CW-CEST MRI for exchange rates below 50 s−1, as confirmed experimentally using a multi-compartment pH phantom. Moreover, acute stroke animals were imaged with both pulsed- and CW- amide protons CEST MRI, which showed similar contrast. In summary, our study elucidated the RF irradiation dependence of pulsed-CEST MRI contrast, providing useful insights to guide its experimental optimization and quantification. PMID:21437977

  8. Patterns of Immunotoxicity Associated with Chronic as Compared with Acute Exposure to Chemical or Physical Stressors and their Relevance with Regard to the Role of Stress and with Regard to Immunotoxicity Testing

    PubMed Central

    Pruett, Stephen B.; Fan, Ruping; Zheng, Qiang; Schwab, Carlton

    2009-01-01

    Previous studies have demonstrated that the stress response induced by some drugs and chemicals contributes in a predictable way to alteration of particular immunological parameters in mice. It has not been determined if mice can become tolerant or habituated with regard to the stress response and consequent immunological effects. Addressing this issue was the purpose of the present study. Mice were dosed daily for 28 days with atrazine, ethanol, propanil, or subjected to restraint, which are known to induce neuroendocrine stress responses and thereby to alter several immunological parameters. On day 29, a blood sample was taken and the spleen was removed for analysis of cellular phenotypes, differential cell counts (for blood), and natural killer (NK) cell activity. Corticosterone concentration at various times after dosing (or restraint) was also measured. Comparison of these results with results from previous studies with a single acute exposure revealed that the corticosterone response was almost completely absent in mice treated with ethanol, reduced in mice treated with restraint and propanil, and for atrazine the response was the same as noted for acute exposure. In most cases, the changes in immunological parameters were consistent with expectations based on these corticosterone responses. However, in a few cases (e.g., NK cell activity), it was clear that there were effects not mediated by stress. These results indicate that the nature of the stressor determines whether mice become tolerant with regard to the stress response and consequent immunological effects. This finding has practical implications for safety testing in mice. PMID:19357072

  9. Acute and delayed toxicities of total body irradiation

    SciTech Connect

    Deeg, H.J.

    1983-12-01

    Total body irradiation is being used with increasing frequency for the treatment of lymphopoietic malignancies and in preparation for marrow transplantation. Acute toxicities include reversible gastroeneritis, mucositis, myelosuppression alopecia. As the success of treatment improves and more patients become long-term survivors, manifestations of delayed and chronic toxicity become evident. These include impairment of growth and development, gonadal failure and sterility, cataract formation and possibly secondary malignancies. The contribution of total body irradiation to the development of pneumonitis and pulmonary fibrosis is still poorly understood. Some of these changes are reversible or correctable, whereas others are permanent. Nevertheless, until equally effective but less toxic regimens become available, total body irradiation appears to be the treatment of choice to prepare patients with leukemia for marrow transplantation.

  10. The Case of a Zebra That Was Misdiagnosed as a Horse: Pulmonary Tumor Thrombotic Microangiopathy, a New Paraneoplastic Syndrome, Mimicking PD-1-Induced Pneumonitis

    PubMed Central

    Carter, Corey A.; Browning, Robert; Oronsky, Bryan T.; Scicinski, Jan J.; Brzezniak, Christina

    2016-01-01

    A case report of a 47-year-old woman with triple-negative breast cancer on a clinical trial called PRIMETIME (NCT02518958) who received the anti-PD-1 inhibitor nivolumab and the experimental anticancer agent RRx-001 is presented. Although initially diagnosed and treated for anti-PD-1-induced pneumonitis, clinical and radiological abnormalities triggered further investigation, leading to the diagnosis of pulmonary tumor thrombotic microangiopathy (PTTM). This example highlights the importance of exercising due diligence in determining immune-related adverse events and suggests that PD-1-induced pneumonitis should be a diagnosis of exclusion rather than a diagnosis by default. A case history and review of the literature are presented for PTTM, which we propose to define as a paraneoplastic syndrome. PMID:26933422

  11. A combination of intravenous immunoglobulin and pulse methylprednisolone extended survival in pulmonary alveolar proteinosis with chronic interstitial pneumonitis: a case report.

    PubMed

    Jirarattanasopa, Nongnapa; Tantikul, Chutsumarn; Vichyanond, Pakit; Pacharn, Punchama; Visitsunthorn, Nualanong; Suttinont, Panthep; Jirapongsananuruk, Orathai

    2010-01-01

    Pulmonary alveolar proteinosis (PAP) is characterized by intra-alveolar accumulation of lipoproteinaceous material. The severe chronic pulmonary disease and susceptibility to pulmonary infection is a prominent feature of the disease. We reported a case of postnatal-onset PAP and chronic interstitial pneumonitis in a girl with chronic respiratory distress since she was 5 months of age. A lung biopsy confirmed the diagnosis. The therapeutic bronchoalveolar lavages, a short trial of granulocyte colony-stimulation factor (G-CSF) and a combination of low dose methylprednisolone and hydroxychloroquine were used at different times without noting satisfactory improvement. Intravenous immunoglobulin (IVIG) and pulse methylprednisolone were given monthly with gradual recovery. She did not require oxygen supplement after 21 months of this combination. Our report suggested that IVIG and pulse methylprednisolone might have a potential role in the treatment of PAP with chronic interstitial pneumonitis. PMID:21038791

  12. A Novel Two-Step Hierarchial Quantitative Structure-Activity Relationship Modeling Workflow for Predicting Acute Toxicity of Chemicals in Rodents

    EPA Science Inventory

    Background: Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Methods and results: A database co...

  13. Acute sacroiliitis.

    PubMed

    Slobodin, Gleb; Rimar, Doron; Boulman, Nina; Kaly, Lisa; Rozenbaum, Michael; Rosner, Itzhak; Odeh, Majed

    2016-04-01

    The purpose of this study was to review the data on the etiology, risk factors, clinical presentations, and diagnosis of acute sacroiliitis. A Pubmed search utilizing the indexing term "acute sacroiliitis" was conducted and the data pertinent to the aim of the review was extracted and organized in accordance with the preplanned structure of the manuscript. The diagnosis of acute sacroiliitis is often challenging because of both the relative rarity of this presentation and diverse character of acute sacroiliac pain, frequently mimicking other, more prevalent disorders. Technetium bone scintigraphy can localize the disease process to the sacroiliac joint, while computed tomography or magnetic resonance imaging can be used for the detailed characterization and the extent of the disease as well as the diagnosis of complications. Pyogenic sacroiliitis is by far the most common cause of acute sacroiliitis. Brucellosis, acute sacroiliitis in the course of reactive arthritis, and crystalline-induced sacroiliitis frequently imitate pyogenic sacroiliitis. Acute sacroiliitis can rarely be also related to hematological malignancies or treatment with isotretinoin. Awareness to the possibility of acute sacroiliitis and a thorough physical examination are the necessary prerequisites to its timely diagnosis, while the appropriate laboratory and imaging studies should confirm the precise diagnosis and direct the appropriate treatment strategy. PMID:26847855

  14. Intensity-Modulated Radiotherapy Might Increase Pneumonitis Risk Relative to Three-Dimensional Conformal Radiotherapy in Patients Receiving Combined Chemotherapy and Radiotherapy: A Modeling Study of Dose Dumping

    SciTech Connect

    Vogelius, Ivan S.; Westerly, David C.; Cannon, George M.; Mackie, Thomas R.; Mehta, Minesh P.; Sugie, Chikao; Bentzen, Soren M.

    2011-07-01

    Purpose: To model the possible interaction between cytotoxic chemotherapy and the radiation dose distribution with respect to the risk of radiation pneumonitis. Methods and Materials: A total of 18 non-small-cell lung cancer patients previously treated with helical tomotherapy at the University of Wisconsin were selected for the present modeling study. Three treatment plans were considered: the delivered tomotherapy plans; a three-dimensional conformal radiotherapy (3D-CRT) plan; and a fixed-field intensity-modulated radiotherapy (IMRT) plan. The IMRT and 3D-CRT plans were generated specifically for the present study. The plans were optimized without adjusting for the chemotherapy effect. The effect of chemotherapy was modeled as an independent cell killing process by considering a uniform chemotherapy equivalent radiation dose added to all voxels of the organ at risk. The risk of radiation pneumonitis was estimated for all plans using the Lyman and the critical volume models. Results: For radiotherapy alone, the critical volume model predicts that the two IMRT plans are associated with a lower risk of radiation pneumonitis than the 3D-CRT plan. However, when the chemotherapy equivalent radiation dose exceeds a certain threshold, the radiation pneumonitis risk after IMRT is greater than after 3D-CRT. This threshold dose is in the range estimated from clinical chemoradiotherapy data sets. Conclusions: Cytotoxic chemotherapy might affect the relative merit of competing radiotherapy plans. More work is needed to improve our understanding of the interaction between chemotherapy and the radiation dose distribution in clinical settings.

  15. Lochgoilhead fever: outbreak of non-pneumonic legionellosis due to Legionella micdadei.

    PubMed

    Goldberg, D J; Wrench, J G; Collier, P W; Emslie, J A; Fallon, R J; Forbes, G I; McKay, T M; Macpherson, A C; Markwick, T A; Reid, D

    1989-02-11

    Analysis of case histories from 187 people who had visited a hotel and leisure complex in Lochgoilhead, a village on the west coast of Scotland, indicated that 170 had had an acute illness characterised by headache, fatigue, arthralgia, myalgia, cough, and breathlessness. These symptoms were consistent with Pontiac fever-like illness. Legionella micdadei was isolated from the leisure complex whirlpool spa at the time that 60 of 72 individuals with symptoms seroconverted to L micdadei antigen. This outbreak is thought to be the first of a Pontiac fever-like illness ascribed to L micdadei and the first large-scale outbreak of its kind to have occurred outside North America. Whirlpool spas can be a major reservoir of legionella organisms; they must therefore be properly maintained and operated to prevent outbreaks of infection. PMID:2563467

  16. Evaluation of chemical mediators and cellular response during acute and chronic gut inflammatory response induced by dextran sodium sulfate in mice.

    PubMed

    Bento, Allisson Freire; Leite, Daniela Ferraz Pereira; Marcon, Rodrigo; Claudino, Rafaela Franco; Dutra, Rafael Cypriano; Cola, Maíra; Martini, Alessandra Cadete; Calixto, João B

    2012-12-01

    Inflammatory bowel disease (IBD) affects millions of people worldwide but its pathophysiology remains unclear. Therefore, experimental models of colitis have contributed crucially for the understanding of IBD, and also in the investigations for effective therapies. Herein we investigated the kinetics of inflammatory mediator production and cell infiltration during acute and chronic dextran sodium sulfate (DSS)-induced colitis. The induction phases with DSS were characterized by severe disease activity with massive colonic polymorphonuclear infiltration and increased levels of tumor necrosis factor-α (TNF-α), keratinocyte-derived chemokine (CXCL1/KC), interleukin (IL)-17 and vascular adhesion molecule-1 (VCAM-1). Interestingly, in the recovery periods, we found marked increase of anti-inflammatory mediators IL-10, IL-4, transforming growth factor-β (TGF-β) and cyclooxygenase 2 (COX-2) that seems be essential for the resolution of intestinal inflammation. Furthermore, nuclear factor κB (NFκB) and regulatory T cell marker forkhead box P3 (FoxP3) were increased gradually during experimental colitis, demonstrating a discrepant profile response and evident immune disbalance in the chronic phase of intestinal mucosal inflammation. Taken together, these results provide valuable information for studies on DSS-induced colitis and especially for the identification of biomarkers that predict disease course and possible therapeutic interventions. PMID:23000912

  17. Acute malocclusion.

    PubMed

    Dupont, John S

    2006-01-01

    Acute malocclusion can result from disturbances in the maxillary/mandibular tooth relationship. These alterations in the occlusal position can result from high fillings, sinus problems, abscesses, periodontal disease, and moving or erupting teeth. Conditions seen less frequently include acute malocclusions secondary to an event (such as trauma) that make a stable dental relationship an unstable one. Patients can demonstrate any of a number of clinical conditions that interfere with their comfort and ability to function. This article provides information on some of the less familiar causes of acute malocclusion. PMID:16689064

  18. Different characteristics associated with intensive care unit transfer from the medical ward between patients with acute exacerbations of chronic obstructive pulmonary disease with and without pneumonia

    PubMed Central

    Shin, Hong-Joon; Park, Cheol-Kyu; Kim, Tae-Ok; Ban, Hee-Jung; Oh, In-Jae; Kim, Yu-Il; Kwon, Yong-Soo; Kim, Young-Chul

    2016-01-01

    Background The rate of hospitalization due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is increasing. Few studies have examined the clinical, laboratory and treatment differences between patients in general wards and those who need transfer to an intensive care unit (ICU). Methods We retrospectively reviewed clinical, laboratory, and treatment characteristics of 374 patients who were initially admitted to the general ward at Chonnam National University Hospital in South Korea due to AECOPD (pneumonic, 194; non-pneumonic, 180) between January 2008 and March 2015. Of these patients, 325 were managed at the medical ward during their hospitalization period (ward group), and 49 required ICU transfer (ICU group). We compared the clinical, laboratory, and treatment characteristics associated with ICU transfer between patients with AECOPD with and without pneumonia. Results Male patients were 86.5% in the ward group and 79.6% in the ICU group. High glucose levels [median 154.5 mg/dL, interquartile range (IQR) 126.8–218.3 in ICU group vs. median 133.0, IQR 109.8–160.3 in ward group], high pneumonia severity index scores (median 100.5, IQR 85.5–118.5 vs. median 86.0, IQR 75.0–103.5), low albumin levels (median 2.9 g/dL, IQR 2.6–3.6 vs. median 3.4, IQR 3.0–3.7), and anemia (73.3% vs. 43.3%) independently increased the risk of ICU transfer in the pneumonic AECOPD group. High PaCO2 levels (median 53.1 mmHg in ICU group, IQR 38.5–84.6 vs. median 39.7, IQR 34.2–48.6 in ward group) independently increased the risk of ICU transfer in the non-pneumonic AECOPD group. Treatment with systemic corticosteroids (≥30 mg of daily prednisolone) during hospitalization in the medical ward independently reduced the risk of ICU transfer in both groups. Conclusions The characteristics associated with ICU transfer differed between the pneumonic and non-pneumonic AECOPD groups, and systemic corticosteroids use was associated with lower rate of ICU

  19. Analysis of clinical and dosimetric factors associated with treatment-related pneumonitis (TRP) in patients with non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT)

    SciTech Connect

    Wang Shulian; Liao Zhongxing . E-mail: zliao@mail.mdanderson.org; Wei Xiong; Liu, Helen H.; Tucker, Susan L.; Hu Chaosu; Mohan, Rodhe; Cox, James D.; Komaki, Ritsuko

    2006-12-01

    Purpose: To investigate factors associated with treatment-related pneumonitis in non-small-cell lung cancer patients treated with concurrent chemoradiotherapy. Patients and Methods: We retrospectively analyzed data from 223 patients treated with definitive concurrent chemoradiotherapy. Treatment-related pneumonitis was graded according to Common Terminology Criteria for Adverse Events version 3.0. Univariate and multivariate analyses were performed to identify predictive factors. Results: Median follow-up was 10.5 months (range, 1.4-58 months). The actuarial incidence of Grade {>=}3 pneumonitis was 22% at 6 months and 32% at 1 year. By univariate analyses, lung volume, gross tumor volume, mean lung dose, and relative V5 through V65, in increments of 5 Gy, were all found to be significantly associated with treatment-related pneumonitis. The mean lung dose and rV5-rV65 were highly correlated (p < 0.0001). By multivariate analysis, relative V5 was the most significant factor associated with treatment-related pneumonitis; the 1-year actuarial incidences of Grade {>=}3 pneumonitis in the group with V5 {<=}42% and V5 >42% were 3% and 38%, respectively (p = 0.001). Conclusions: In this study, a number of clinical and dosimetric factors were found to be significantly associated with treatment-related pneumonitis. However, rV5 was the only significant factor associated with this toxicity. Until it is better understood which dose range is most relevant, multiple clinical and dosimetric factors should be considered in treatment planning for non-small-cell lung cancer patients receiving concurrent chemoradiotherapy.

  20. Acute Bronchitis

    MedlinePlus

    ... bronchitis? Acute bronchitis is almost always caused by viruses that attack the lining of the bronchial tree ... infection. As your body fights back against these viruses, more swelling occurs and more mucus is produced. ...

  1. Acute Pericarditis

    MedlinePlus

    ... large pericardial effusions). Acute pericarditis usually responds to colchicine or NSAIDs (such as aspirin and ibuprofen ) taken ... reduce pain but relieves it by reducing inflammation. Colchicine also decreases the chance of pericarditis returning later. ...

  2. Recurrent Interstitial Pneumonitis in a Patient with Entero-Behçet's Disease Initially Treated with Mesalazine

    PubMed Central

    Miyamura, Tomoya; Wu, Brian; Suematsu, Eiichi

    2016-01-01

    A 65-year-old man with entero-Behçet's disease (BD) being treated with mesalazine was presented to our hospital complaining of dyspnea. Computed tomography (CT) of the chest showed ground-glass opacities and he was initially diagnosed with mesalazine-induced interstitial pneumonitis (IP). Besides the discontinuation of mesalazine, a high dose of oral prednisolone was administered and the patient seemed to recover. However, four months later, dyspnea recurred and repeated CT revealed more extensive pulmonary infiltration despite steroid therapy. After the exclusion of infections, we suspected either a recurrence of mesalazine-induced IP or BD-related IP as a clinical manifestation of BD. The patient was treated with intravenous methylprednisolone and cyclophosphamide, followed by orally administered azathioprine, based on the assumption of underlying vasculitis. Thereafter, his condition improved. BD-related IP is an extremely rare condition with limited reports in the literature. Mesalazine-induced IP is also uncommon but the prognosis is generally good after discontinuation of mesalazine with or without steroid therapy. We discuss an extremely rare case, especially focusing on BD-related IP and mesalazine-induced IP as a potential cause of recurrent IP in a patient with entero-BD. PMID:27429824

  3. Radiation pneumonitis in patients with lung and mediastinal tumours: a retrospective study of risk factors focused on pulmonary emphysema

    PubMed Central

    Kimura, T; Togami, T; Takashima, H; Nishiyama, Y; Ohkawa, M; Nagata, Y

    2012-01-01

    Objectives To evaluate the impact of pulmonary emphysema (PE) on the incidence and severity of radiation pneumonitis (RP) in patients with lung and mediastinal tumours. Methods 92 patients were enrolled. Involved-field radiation therapy (non-small cell carcinoma or mediastinal tumours in 69 patients; median 70 Gy) and accelerated hyperfractionation (limited disease small cell carcinoma in 23 patients; median 45 Gy) were performed. Common Terminology Criteria for Adverse Events v.3.0 was used to evaluate RP and the relationship with the percentage of pulmonary volume irradiated to >20 Gy (V20) and PE. PE was diagnosed by the presence of low-attenuation areas (LAAs) on CT scans and was classified into Grades 0–4 according to the extent of the LAAs. Results The median follow-up time was 16 months. The 6-month cumulative incidence of RP at Grade 3 or greater was 7.7% and 34.1% in patients with a V20 of <25% and ≥25%, respectively (p=0.017). In patients with PE Grades 0, 1, 2 and 3 or greater, the incidence of RP was 16.5%, 9.1%, 8.6% and 54.0%, respectively. As the PE Grade increased, the incidence of RP also increased significantly. Conclusion The incidence and severity of RP are significantly higher in patients with a high V20 value as well as in those with severe PE. PMID:21385918

  4. [Intraspecies diversity of Trichosporon asahii as the causative agent of opportunistic fungal infection and summer-type hypersensitivity pneumonitis].

    PubMed

    Sugita, Takashi

    2003-01-01

    Trichosporon asahii is the major causative agent of the opportunistic infection trichosporonosis, and also causes summer-type hypersensitivity pneumonitis (SHP). Random amplification of polymorphic DNA analysis was used to determine the intraspecies diversity of T. asahii isolates from clinical specimens,the houses of SHP patients, and environmental material. Clinical isolates formed a cluster, characterized by a 90% matching coefficient, but they did not cluster with strains isolated from SHP patients houses or environmental sources. The biochemical characteristics of T. asahii isolates from the three sources were compared, and a phenogram was constructed. One of the two clusters included most of the clinical isolates and strains isolated from the houses, and the other cluster included most of the environmental isolates. There was a remarkable difference in the abilities of the strains belonging to these clusters to utilize several compounds. These results suggest that the genetic diversity and biochemical characteristics of T. asahii are related to the source of the isolates. In addition, based on the IGS1 sequence, which is located between the 26S and 5S rRNA genes, we identified five genotypes of T. asahii, which is a major causative agent of deep-seated trichosporonosis. Of the five genotypes, three were isolates that originated in Japan, whereas two were American isolates. IGS sequence analysis shows great potential as a new epidemiological tool. PMID:12590253

  5. Acute physiological responses while wearing various configurations of the MCU-2/P groundcrew chemical defense mask. Final report, 19 January 1990-19 July 1991

    SciTech Connect

    Antunano, M.J.; Chen, Y.T.; Constable, S.H.

    1992-10-01

    Resistance to breathing is a major factor that determines individual tolerance to physical work while wearing a protective mask. This study evaluated some of the acute effects associated with the use of the MCU-2/P mask. Three MCU-2/P mask configurations (MC) were tested: mask + 1 filter (MCU-IF), mask + 2 filters in parallel (MCU-2F), and mask + 1 filter + air blower (MCU-lAB). The air blower provided 65 L min-1 (2.3 cfm) of ambient air through the filter. Five subjects pedaled a cycle ergometer at 2 workloads (60 120 watts). Each MC was tested consecutively for 5 min under each workload, for a total of 30 min per experiment. Each subject repeated the experiment three times while randomizing the mask/workload test order. Variables measured included heart rate, respiratory rate, tidal volume, minute volume, inspiratory and expiratory mask cavity pressures, perceived inspiratory expiratory effort, and overall breathing discomfort. The lowest inspiratory resistance was observed with the MCU1AB, followed by MCU-2F and MCU-IF. Subjects experienced less breathing effort and discomfort with the MCU-IAB, followed by a more modest reduction with the MCU-2F. Heart rates, respiratory rates, tidal volumes, and minute volumes showed no correlation with the three levels of inspiratory resistance, but were related to workload. The best approach to reduce the respiratory burden imposed by the MCU-2/P mask is to provide powered ventilation through the filter. Unfortunately, this approach creates logistical problems. A more practical approach may simply be to attach a second filter canister to the mask. Breathing resistance, M17 Mask, MCU-2/P Mask, Physical exercise, Breathing discomfort, Manikin testing, Human testing.

  6. The identification and antimicrobial susceptibility of anaerobic bacteria from pneumonic cattle lungs.

    PubMed Central

    Chirino-Trejo, J M; Prescott, J F

    1983-01-01

    One hundred and forty-four lungs obtained postmortem from cattle with pneumonia were cultured for anaerobic bacteria. Forty-five lungs yielded 73 anaerobic isolates belonging to 20 species. The number of isolations of anaerobes from acute fibrinous or suppurative bronchopneumonias (32.5%) was slightly lower than from similar chronic bronchopneumonias (36.5%). Anaerobes were not recovered from 15 lungs showing macroscopic changes not of bacterial origin, nor from 13 healthy lungs. The predominant genera isolated were Bacteroides, Peptococcus, Fusobacterium and Clostridium. The most common species were P. indolicus (15 isolates), B. asaccharolyticus (nine), F. necrophorum (six), C. perfringens (four) and B. fragilis (four). There was a significant correlation between the presence of Corynebacterium pyogenes (p less than 0.001) or Escherichia coli (p less than 0.01) and the presence of anaerobes in the lungs. The isolated anaerobic bacteria were generally susceptible to ampicillin, penicillin G, cefoxitin, cephalothin, clindamycin, chloramphenicol, erythromycin, tetracycline and metronidazole. The B. fragilis and C. perfringens isolates showed multiple antibiotic resistance, and five P. indolicus isolates were resistant to tetracycline. PMID:6640410

  7. Acute myelogenous leukemia (AML) - children

    MedlinePlus

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  8. Acute and Long-Term Response of Dopamine Nigrostriatal Synapses to a Single Low Dose Episode of 3-Nitropropionic Acid-Mediated Chemical Hypoxia

    PubMed Central

    Crawford, Cynthia A.; Akopian, Garnik; Ring, Justin; Jakowec, Michael W.; Petzinger, Giselle M.; Andersen, Julie K.; Vittozzi-Wong, Philip; Wang, Kristie; Farley, Cristal M.; Charntikov, Sergios; Mitroi, Danut; Beal, M. Flint; Chow, Robert; Walsh, John P.

    2010-01-01

    The goal of the present investigation was to determine the persistence of striatal dopaminergic dysfunction after a mild chemically-induced hypoxic event in Fisher 344 rats. To this end, we gave a single injection of the mitochondrial complex II inhibitor 3-nitropropionic acid (3-NP; 16.5 mg/kg, i.p.) to 2 month old male F344 rats and measured various indices of striatal dopaminergic functioning and lipid peroxidation over a 3 month span. Separate groups of rats were used to measure rod walking, evoked dopamine (DA) release, DA content, MDA accumulation, DA receptor binding, and tyrosine hydroxylase activity. The results showed that 3-NP exposure reduced most measures of DA functioning including motoric ability, DA release, and D2 receptor densities for 1 to 3 months post drug administration. Interestingly, DA content was reduced 1 week after 3-NP exposure, but rose to 147% of control values 1 month after 3-NP treatment. MDA accumulation, a measure of lipid peroxidation activity, was increased 24 hr and 1 month after 3-NP treatment. 3-NP did not affect tyrosine hydroxylase activity, suggesting that alterations in DA functioning were not the result of nigrostriatal terminal loss. These data demonstrate that a brief mild hypoxic episode caused by 3-NP exposure has long-term detrimental effects on the functioning of the nigrostriatal DA system. PMID:20730800

  9. Demonstrating approaches to chemically modify the surface of Ag nanoparticles in order to influence their cytotoxicity and biodistribution after single dose acute intravenous administration.

    PubMed

    Pang, Chengfang; Brunelli, Andrea; Zhu, Conghui; Hristozov, Danail; Liu, Ying; Semenzin, Elena; Wang, Wenwen; Tao, Wuqun; Liang, Jingnan; Marcomini, Antonio; Chen, Chunying; Zhao, Bin

    2016-03-01

    With the advance in material science and the need to diversify market applications, silver nanoparticles (AgNPs) are modified by different surface coatings. However, how these surface modifications influence the effects of AgNPs on human health is still largely unknown. We have evaluated the uptake, toxicity and pharmacokinetics of AgNPs coated with citrate, polyethylene glycol, polyvinyl pyrolidone and branched polyethyleneimine (Citrate AgNPs, PEG AgNPs, PVP AgNPs and BPEI AgNPs, respectively). Our results demonstrated that the toxicity of AgNPs depends on the intracellular localization that was highly dependent on the surface charge. BPEI AgNPs (ζ potential = +46.5 mV) induced the highest cytotoxicity and DNA fragmentation in Hepa1c1c7. In addition, it showed the highest damage to the nucleus of liver cells in the exposed mice, which is associated with a high accumulation in liver tissues. The PEG AgNPs (ζ potential = -16.2 mV) showed the cytotoxicity, a long blood circulation, as well as bioaccumulation in spleen (34.33 µg/g), which suggest better biocompatibility compared to the other chemically modified AgNPs. Moreover, the adsorption ability with bovine serum albumin revealed that the PEG surface of AgNPs has an optimal biological inertia and can effectively resist opsonization or non-specific binding to protein in mice. The overall results indicated that the biodistribution of AgNPs was significantly dependent on surface chemistry: BPEI AgNPs > Citrate AgNPs = PVP AgNPs > PEG AgNPs. This toxicological data could be useful in supporting the development of safe AgNPs for consumer products and drug delivery applications. PMID:25962681

  10. Acute Pneumonia.

    PubMed

    Arshad, Hammad; Fasanya, Adebayo; Cheema, Tariq; Singh, Anil C

    2016-01-01

    Acute pneumonia is an active infection of the lungs that results when an individual at risk gets exposed to a particular microbiological pathogen. Acute pneumonia is the leading cause of death in the United States that is attributable to an infection. The risk factors, pathogenesis, and microbiological organisms involved differ if the pneumonia develops in the community versus health care-associated environment. The development of concise and comprehensive guidelines has led to an improvement in the management of the problem. However, the emergence of multidrug-resistant organisms and the increase in the percentage of elderly population keep mortality risk very substantial. PMID:26919676

  11. Endoscopic autofluorescence micro-spectroimaging of alveoli: comparative spectral analysis of amiodarone-induced pneumonitis patients and healthy smokers

    NASA Astrophysics Data System (ADS)

    Bourg-Heckly, G.; Vever-Bizet, C.; Blondel, W.; Salaün, M.; Thiberville, L.

    2011-03-01

    Fibered confocal fluorescence microscopy (FCFM) with spectroscopic analysis capability was used during bronchoscopy, at 488nm excitation, to record autofluorescence images and associated emission spectra of the alveoli of 5 healthy smoking volunteers and 7 non-smoking amiodarone-induced pneumonitis (AIP) patients. Alveolar fluorescent cellular infiltration was observed in both groups. Our objective was to assess the potential of spectroscopy in differentiating these two groups. Methods: We previously demonstrated that in healthy smokers alveolar elastin backbone and tobacco tar contained in macrophages contribute to the observed signal. Each normalized spectrum was modeled as a linear combination of 3 components: Sexp(λ) = Ce.Se(λ)+Ct.St(λ)+CG.SG(λ), Ce, Ct and CG are amplitude coefficients. Se(λ) and St(λ) are respectively the normalized elastin and tobacco tar emission spectra measured experimentally and SG(λ) a gaussian spectrum with tunable width and central wavelength. Levenbergt-Marquardt algorithm determined the optimal set of coefficients. Results: AIP patient autofluorescence spectra can be uniquely modelized by the linear combination of the elastin spectrum (Ce = 0.61) and of a gaussian spectrum (center wavelength 550nm, width 40nm); the tobacco tar spectrum coefficient Ct is found to be zero. For healthy smoking volunteers, only two spectral components were considered: the tobacco tar component (Ct = 1,03) and the elastin component (Ce = 0). Conclusion: Spectral analysis is able to distinguish cellular infiltrated images from AIP patients and healthy smoking volunteers. It appears as a powerful complementary tool for FCFM.

  12. Effect of induction chemotherapy on estimated risk of radiation pneumonitis in bulky non–small cell lung cancer

    SciTech Connect

    Amin, Neha P.; Miften, Moyed; Thornton, Dale; Ryan, Nicole; Kavanagh, Brian; Gaspar, Laurie E

    2013-10-01

    Patients with bulky non–small cell lung cancer (NSCLC) may be at a high risk for radiation pneumonitis (RP) if treated with up-front concurrent chemoradiation. There is limited information about the effect of induction chemotherapy on the volume of normal lung subsequently irradiated. This study aims to estimate the reduction in risk of RP in patients with NSCLC after receiving induction chemotherapy. Between 2004 and 2009, 25 patients with Stage IV NSCLC were treated with chemotherapy alone (no surgery or radiation therapy [RT]) and had computed tomography (CT) scans before and after 2 cycles of chemotherapy. Simulated RT plans were created for the prechemotherapy and postchemotherapy scans so as to deliver 60 Gy to the thoracic disease in patients who had either a >20% volumetric increase or decrease in gross tumor volume (GTV) from chemotherapy. The prechemotherapy and postchemotherapy scans were analyzed to compare the percentage of lung volume receiving≥20 Gy (V20), mean lung dose (MLD), and normal tissue complication probability (NTCP). Eight patients (32%) had a GTV reduction >20%, 2 (8%) had GTV increase >20%, and 15 (60%) had stable GTV. In the 8 responders, there was an absolute median GTV decrease of 88.1 cc (7.3 to 351.6 cc) or a 48% (20% to 62%) relative reduction in tumor burden. One had >20% tumor progression during chemotherapy, yet had an improvement in dosimetric parameters postchemotherapy. Among these 9 patients, the median decrease in V20, MLD, and NTCP was 2.6% (p<0.01), 2.1 Gy (p<0.01), and 5.6% (p<0.01), respectively. Less than one-third of patients with NSCLC obtain >20% volumetric tumor reduction from chemotherapy alone. Even with that amount of volumetric reduction, the 5% reduced risk of RP was only modest and did not convert previously ineligible patients to safely receive definitive thoracic RT.

  13. Acquired immunodeficiency syndrome (AIDS) with lymphocytic interstitial pneumonitis (LIP) in a multi transfused child with thalassemia major.

    PubMed

    Sen, S; Goyal, R S; Kumar, A; Pande, I; Khare, S D; Chattopadhya, D; Malaviya, A N

    1992-11-01

    The case of a 10.5-year-old girl, who was diagnosed with a case of thalassemia major at the age of 8 months and had been on regular blood transfusions since then, is related. Donor screening for HIV was started in mid-1988, thus she had received unscreened blood for a number of years. In February 1991, she presented with a dry persistent cough, moderate grade continuous fever, and breathlessness on exertion for over 2 weeks. Chest X-ray showed bilateral infiltrations. She was put on penicillin and chloramphenicol with a provisional diagnosis of bronchopneumonia. In March 1991, she had to be hospitalized for impending respiratory failure. After treatment with intravenous fluids and parenteral antimicrobials, her condition stabilized and she was discharged. In April 1991, she was readmitted because of complaints of difficulty in swallowing and weight loss. Her chest signs had persisted and she had developed oropharyngeal candidiasis with ulcerations. She also had alopecia, a generalized lymphadenopathy, digital clubbing, and bilateral parotid enlargement. Candidiasis responded to vigorous therapy with clotrimazole. Fine needle aspiration of lymph node showed a reactive hyperplasia. HIV antibodies were detected in the serum with ELISA and confirmed by Western blot. Immunologic tests showed evidence of severe immunodeficiency. The Multitest CMI, which simultaneously tests delayed skin hypersensitivity to seven common recall antigens, was totally nonreactive. She was classified as having AIDS according to World Health Organization criteria for children under 13 years of age. The diagnosis of lymphocytic interstitial pneumonitis (LIP) was also made based on the symptoms. Oral prednisolone was given 2 mg/kg/day in 3 divided doses for a month. The cough and dyspnea showed great improvement and the parotid swellings disappeared; lymphadenopathy, clubbing, and alopecia, however, persisted. The child was kept on maintenance therapy of prednisolone and on alternate day co

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

    SciTech Connect

    Xiong, Huihua; Liao, Zhongxing; Liu, Zhensheng; Xu, Ting; Wang, Qiming; Liu, Hongliang; Komaki, Ritsuko; Gomez, Daniel; Wang, Li-E; Wei, Qingyi

    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.

  15. Chronic hypersensitivity pneumonitis caused by Saccharopolyspora rectivirgula is not associated with a switch to a Th2 response.

    PubMed

    Andrews, Kelly; Ghosh, Manik C; Schwingshackl, Andreas; Rapalo, Gabriel; Luellen, Charlean; Waters, Christopher M; Fitzpatrick, Elizabeth A

    2016-03-01

    Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease results in alveolitis and granuloma formation and may progress to a chronic form associated with fibrosis; a greater understanding of the immunopathogenic mechanisms leading to chronic HP is needed. We used the Saccharopolyspora rectivirgula (SR) mouse model of HP to determine the extent to which a switch to a Th2-type immune response is associated with chronic HP. Exposure of wild-type (WT) and tlr2/9(-/-) mice to SR for 14 wk resulted in neutrophilic and lymphocytic alveolitis that was not dependent on Toll-like receptors (TLRs) 2 and 9. Long-term exposure of WT mice to SR resulted in a significant increase in collagen deposition, protein leakage, and IL-1α accompanied by a decrease in quasistatic compliance and total lung capacity compared with unexposed mice. This was associated with an increase in IL-17 but not IL-4 production or recruitment of Th2 cells. tlr2/9(-/-) mice exhibited an increase in protein leakage but less IL-1α and collagen deposition in the lungs compared with WT mice, yet they still displayed a decrease in quasistatic compliance, although total lung capacity was not affected. These mice exhibited an increase in both IL-13 and IL-17, which suggests that IL-13 may ameliorate some of the lung damage caused by long-term SR exposure. Our results suggest that lung pathology following long-term SR exposure in WT mice is associated with the IL-17 response and that TLRs 2 and 9 may inhibit the development of the IL-13/Th2 response. PMID:26719148

  16. Severe anemia, gastric ulcer, pneumonitis and cholangitis in a liver transplant patient: multiple organic dysfunction and one etiology: a case report.

    PubMed

    García-Pajares, F; Santos-Santamarta, F; Fernández-Fontecha, E; Sánchez-Ocaña, R; Amo-Alonso, R; Loza-Vargas, A; Madrigal, B; Pérez-Saborido, B; Almohalla, C; Sánchez-Antolín, G

    2015-01-01

    Cytomegalovirus (CMV) is the most common viral pathogen that negatively affects the outcome of liver transplantation. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases it invades tissues, including the transplanted allograft. In addition, CMV has been significantly associated with an increased predisposition to allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survivals. We carried out a study on a Spanish adult liver transplant recipient who rapidly presented anemia and was diagnosed as having Coomb negative (nonimmune) hemolytic anemia, gastric ulcer, pneumonitis, and cholangitis associated with a CMV infection. PMID:25645792

  17. Recombinant V antigen protects mice against pneumonic and bubonic plague caused by F1-capsule-positive and -negative strains of Yersinia pestis.

    PubMed Central

    Anderson, G W; Leary, S E; Williamson, E D; Titball, R W; Welkos, S L; Worsham, P L; Friedlander, A M

    1996-01-01

    The purified recombinant V antigen from Yersinia pestis, expressed in Escherichia coli and adsorbed to aluminum hydroxide, an adjuvant approved for human use, was used to immunize outbred Hsd:ND4 mice subcutaneously. Immunization protected mice from lethal bubonic and pneumonic plague caused by CO92, a wild-type F1+ strain, or by the isogenic F1- strain C12. This work demonstrates that a subunit plague vaccine formulated for human use provides significant protection against bubonic plague caused by an F1- strain (C12) or against substantial aerosol challenges from either F1+ (CO92) or F1-(C12) Y. pestis. PMID:8890210

  18. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  19. [Acute toxic pneumopathies].

    PubMed

    Garnier, R

    1998-06-15

    The nature and extent of the acute injury due to toxic inhalants depend on the inhalant's solubility in water pH and chemical reactivity, on the aerodynamic diameter of particles (when the inhalant is an aerosol), and on the degree of exposure. Initial signs and symptoms indicate upper airways and bronchial irritation. Laryngeal oedema and (or) severe bronchospasm may be rapidly lethal. After cessation of exposure a transient improvement is generally observed; however a delayed pulmonary oedema may occur within the first 48 hours. On the following days, bacterial surinfection is a common complication. Possible long-term sequelae are reactive airways dysfunction syndrome and bronchiolitis obliterans. PMID:9781191

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

    NASA Astrophysics Data System (ADS)

    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

  1. IMRT may increase pneumonitis risk relative to 3D-CRT in patients receiving combined chemotherapy and radiation therapy: a modeling study of dose dumping

    PubMed Central

    Vogelius, Ivan S.; Westerly, David C.; Cannon, George M.; Mackie, Thomas R.; Mehta, Minesh P.; Sugie, Chikao; Bentzen, Søren M.

    2011-01-01

    Purpose To model the possible interaction between cytotoxic chemotherapy and radiation dose distribution with respect to the risk of radiation pneumonitis (RP). Methods and materials Eighteen non-small cell lung cancer patients previously treated with helical tomotherapy at the University of Wisconsin were selected for this modeling study. Three treatment plans were considered in the study: (1) the delivered tomotherapy plans; (2) a 3D conformal radiotherapy (3D-CRT) plan; and (3) a fixed field intensity modulated radiotherapy (IMRT) plan. The IMRT and 3D-CRT plans were generated specifically for this study. Plans were optimized without adjusting for the chemotherapy effect. The effect of chemotherapy was modeled as an independent cell killing process by considering a uniform chemotherapy equivalent radiation dose (CERD) added to all voxels of the organ at risk. Risk of radiation pneumonitis was estimated for all plans using the Lyman and the Critical Volume models. Results For radiation therapy alone, the Critical Volume model predicts that the two IMRT plans are associated with a lower risk of RP than the 3D-CRT plan. However, when the CERD exceeds a certain threshold, the RP risk after IMRT is higher than after 3D-CRT. This threshold dose is in the range estimated from clinical chemo-radiation data sets. Conclusions Cytotoxic chemotherapy may affect the relative merit of competing radiation therapy plans. More work is needed to improve our understanding of the interaction between chemotherapy and radiation dose distribution in clinical settings. PMID:21477946

  2. Comparative Analyses of Transcriptional Profiles in Mouse Organs Using a Pneumonic Plague Model after Infection with Wild-Type Yersinia pestis CO92 and Its Braun Lipoprotein Mutant

    PubMed Central

    Galindo, Cristi L.; Moen, Scott T.; Kozlova, Elena V.; Sha, Jian; Garner, Harold R.; Agar, Stacy L.; Chopra, Ashok K.

    2009-01-01

    We employed Murine GeneChips to delineate the global transcriptional profiles of the livers, lungs, and spleens in a mouse pneumonic plague infection model with wild-type (WT) Y. pestis CO92 and its Braun lipoprotein (Δlpp) mutant with reduced virulence. These organs showed differential transcriptional responses to infection with WT Y. pestis, but the overall host functional processes affected were similar across all three tissues. Gene expression alterations were found in inflammation, cytokine signaling, and apoptotic cell death-associated genes. Comparison of WT and Δlpp mutant-infected mice indicated significant overlap in lipopolysaccharide- (LPS-) associated gene expression, but the absence of Lpp perturbed host cell signaling at critical regulatory junctions resulting in altered immune response and possibly host cell apoptosis. We generated a putative signaling pathway including major inflammatory components that could account for the synergistic action of LPS and Lpp and provided the mechanistic basis of attenuation caused by deletion of the lpp gene from Y. pestis in a mouse model of pneumonic plague. PMID:20145715

  3. Remote monitoring of the progression of primary pneumonic plague in Brown Norway rats in high-capacity, high-containment housing

    PubMed Central

    Coate, Eric A.; Kocsis, Andrew G.; Peters, Kristen N.; Anderson, Paul E.; Ellersieck, Mark R.; Fine, Deborah M.; Anderson, Deborah M.

    2014-01-01

    Development of new vaccines, diagnostics and therapeutics for biodefense or other relatively rare infectious diseases is hindered by the lack of naturally occurring human disease on which to conduct clinical trials of efficacy. To overcome this experimental gap, the U.S. Food and Drug Administration established the Animal Rule, in which efficacy testing in two well-characterized animal models that closely resemble human disease may be accepted in lieu of large scale clinical trials for diseases with limited natural human incidence. In this report, we evaluated the Brown Norway rat as a model for pneumonic plague and describe the natural history of clinical disease following inhalation exposure to Yersinia pestis. In high-capacity, high-containment housing, we monitored temperature, activity, heart rate and rhythm by capturing electronic impulses transmitted from abdominal telemeter implants. Using this system, we show that reduced activity and development of fever are sensitive indications of disease progression. Furthermore, we identified heart arrhythmias as contributing factors to the rapid progression to lethality following the fever response. Together these data validate the Brown Norway rat as an experimental model for human pneumonic plague and provide new insight that may ultimately lead to novel approaches in post-exposure treatment of this devastating infection. PMID:24719212

  4. Acute diarrhea.

    PubMed

    Barr, Wendy; Smith, Andrew

    2014-02-01

    Acute diarrhea in adults is a common problem encountered by family physicians. The most common etiology is viral gastroenteritis, a self-limited disease. Increases in travel, comorbidities, and foodborne illness lead to more bacteria-related cases of acute diarrhea. A history and physical examination evaluating for risk factors and signs of inflammatory diarrhea and/or severe dehydration can direct any needed testing and treatment. Most patients do not require laboratory workup, and routine stool cultures are not recommended. Treatment focuses on preventing and treating dehydration. Diagnostic investigation should be reserved for patients with severe dehydration or illness, persistent fever, bloody stool, or immunosuppression, and for cases of suspected nosocomial infection or outbreak. Oral rehydration therapy with early refeeding is the preferred treatment for dehydration. Antimotility agents should be avoided in patients with bloody diarrhea, but loperamide/simethicone may improve symptoms in patients with watery diarrhea. Probiotic use may shorten the duration of illness. When used appropriately, antibiotics are effective in the treatment of shigellosis, campylobacteriosis, Clostridium difficile, traveler's diarrhea, and protozoal infections. Prevention of acute diarrhea is promoted through adequate hand washing, safe food preparation, access to clean water, and vaccinations. PMID:24506120

  5. Sinusitis (acute)

    PubMed Central

    2008-01-01

    Introduction Acute sinusitis is defined pathologically, by transient inflammation of the mucosal lining of the paranasal sinuses lasting less than 4 weeks. Clinically, it is characterised by nasal congestion, rhinorrhoea, facial pain, hyposmia, sneezing, and, if more severe, additional malaise and fever. It affects 1−5% of the adult population each year in Europe. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with clinically diagnosed acute sinusitis, and with radiologically or bacteriologically confirmed acute sinusitis? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (amoxicillin, co-amoxiclav, doxycycline, cephalosporins, macrolides, different doses [amoxicillin, co-amoxiclav, doxycycline, cephalosporins, macrolides], long-course regimens), antihistamines, cephalosporins or macrolides, decongestants (xylometazoline, phenylephrine, pseudoephedrine), doxycycline, saline nasal washes, steam inhalation, and topical corticosteroids (intra-nasal). PMID:19450327

  6. Sinusitis (acute)

    PubMed Central

    2011-01-01

    Introduction Acute sinusitis is defined pathologically, by transient inflammation of the mucosal lining of the paranasal sinuses lasting less than 4 weeks. Clinically, it is characterised by nasal congestion, rhinorrhoea, facial pain, hyposmia, sneezing, and, if more severe, additional malaise and fever. It affects 1% to 5% of the adult population each year in Europe. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with clinically diagnosed acute sinusitis, and in people with radiologically or bacteriologically confirmed acute sinusitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (amoxicillin, amoxicillin–clavulanic acid [co-amoxiclav], doxycycline, cephalosporins, macrolides; different doses, long-course regimens), antihistamines, decongestants (xylometazoline, phenylephrine, pseudoephedrine), saline nasal washes, steam inhalation, and topical corticosteroids (intranasal). PMID:22189346

  7. Acute glomerulonephritis.

    PubMed

    Yoshizawa, N

    2000-09-01

    Acute glomerulonephritis (AGN) is a representative disease of acute nephritic syndrome characterized by the sudden appearance of edema, hematuria, proteinuria, and hypertension. The prototype of AGN is acute poststreptococcal glomerulonephritis (APSGN). "Nephritogenic streptococci" are defined as organisms that are cultured from a patient who develops AGN. Although only a limited number of M-types of streptococci have been recognized as "nephritogenic streptococci", all M-types of streptococci may have nephritogenic potential because the genes for major putative nephritogenic antigens such as SPEB and NAPIr are found to be present in all group A streptococci thus far examined. Pathogenic mechanisms for APSGN involving both humoral and cell-mediated immunity have been recently proposed. The role of humoral immunity is presumed to be mediated by the in situ formation of nephritogenic streptococcal antigen-antibody complexes and circulating immune complexes. While in the cellular immune component a role for delayed-type hypersensitivity has been suggested to contribute to the pathogenesis of APSGN. PMID:10969898

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

    SciTech Connect

    Liu Hui; Zhang Xu; Vinogradskiy, Yevgeniy Y.; Swisher, Stephen G.; Komaki, Ritsuko; Chang, Joe Y.

    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.

  9. LcrV Delivered via Type III Secretion System of Live Attenuated Yersinia pseudotuberculosis Enhances Immunogenicity against Pneumonic Plague

    PubMed Central

    Sanapala, Shilpa; Henderson, Jeremy C.; Sam, Shandiin; Olinzock, Joseph; Trent, M. Stephen; Curtiss, Roy

    2014-01-01

    Here, we constructed a Yersinia pseudotuberculosis mutant strain with arabinose-dependent regulated and delayed shutoff of crp expression (araC PBAD crp) and replacement of the msbB gene with the Escherichia coli msbB gene to attenuate it. Then, we inserted the asd mutation into this construction to form χ10057 [Δasd-206 ΔmsbB868::PmsbB msbB(EC) ΔPcrp21::TT araC PBAD crp] for use with a balanced-lethal Asd-positive (Asd+) plasmid to facilitate antigen synthesis. A hybrid protein composed of YopE (amino acids [aa]1 to 138) fused with full-length LcrV (YopENt138-LcrV) was synthesized in χ10057 harboring an Asd+ plasmid (pYA5199, yopENt138-lcrV) and could be secreted through a type III secretion system (T3SS) in vitro and in vivo. Animal studies indicated that mice orally immunized with χ10057(pYA5199) developed titers of IgG response to whole-cell lysates of Y. pestis (YpL) and subunit LcrV similar to those seen with χ10057(pYA3332) (χ10057 plus an empty plasmid). However, only immunization of mice with χ10057(pYA5199) resulted in a significant secretory IgA response to LcrV. χ10057(pYA5199) induced a higher level of protection (80% survival) against intranasal (i.n.) challenge with ∼240 median lethal doses (LD50) (2.4 × 104 CFU) of Y. pestis KIM6+(pCD1Ap) than χ10057(pYA3332) (40% survival). Splenocytes from mice vaccinated with χ10057(pYA5199) produced significant levels of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-17 (IL-17) after restimulation with LcrV and YpL antigens. Our results suggest that it is possible to use an attenuated Y. pseudotuberculosis strain delivering the LcrV antigen via the T3SS as a potential vaccine candidate against pneumonic plague. PMID:25114109

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

    SciTech Connect

    Tang, Chad; Gomez, Daniel R.; Wang, Hongmei; Levy, Lawrence B.; Zhuang, Yan; Xu, Ting; Nguyen, Quynh; Komaki, Ritsuko; Liao, Zhongxing

    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.

  11. The acute toxicity of inhaled beryllium metal in rats

    SciTech Connect

    Haley, P.J.; Finch, G.L.; Hoover, M.D.; Cuddihy, R.G. )

    1990-01-01

    The authors exposed rats once by nose only for 50 min to a mean concentration of 800 [mu]g/m[sup 3] of beryllium metal to characterize the acute toxic effects within the lung. Histological changes within the lung and enzyme changes within bronchoalveolar lavage (BAL) fluid were evaluated at 3, 7, 10, 14, 31, 59, 115, and 171 days postexposure (dpe). Beryllium metal-exposed rats developed acute, necrotizing, hemorrhagic, exudative pneumonitis and intraalveolar fibrosis that peaked at 14 dpe. By 31 dpe, inflammatory lesions were replaced by minimal interstitial and intraalveolar fibrosis. Necrotizing inflammation was observed again at 59 dpe which progressed to chronic-active inflammation by 115 dpe. Low numbers of diffusely distributed lymphocytes were also present but they were not associated with granulomas as is observed in beryllium-induced disease in man. Lymphocytes were not elevated in BAL samples collected from beryllium-exposed rats at any time after exposure. Lactate dehydrogenase (LDH), [beta]-glucuronidase, and protein levels were elevated in BAL fluid from 3 through 14 dpe but returned to near normal levels by 31 dpe. LDH increased once again at 59 dpe and remained elevated at 171 dpe. [beta]-Glucuronidase and protein levels were slightly, but not significantly, elevated from 31 through 171 dpe.

  12. Nintedanib Compared With Placebo in Treating Against Radiation-Induced Pneumonitis in Patients With Non-small Cell Lung Cancer That Cannot Be Removed by Surgery and Are Undergoing Chemoradiation Therapy

    ClinicalTrials.gov

    2016-04-27

    Radiation-Induced Pneumonitis; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  13. Association between Genetic Variants in DNA Double-Strand Break Repair Pathways and Risk of Radiation Therapy-Induced Pneumonitis and Esophagitis in Non-Small Cell Lung Cancer

    PubMed Central

    Zhao, Lina; Pu, Xia; Ye, Yuanqing; Lu, Charles; Chang, Joe Y.; Wu, Xifeng

    2016-01-01

    Radiation therapy (RT)-induced pneumonitis and esophagitis are commonly developed side effects in non-small cell lung cancer (NSCLC) patients treated with definitive RT. Identifying patients who are at increased risk for these toxicities would help to maximize treatment efficacy while minimizing toxicities. Here, we systematically investigated single nucleotide polymorphisms (SNPs) within double-strand break (DSB) repair pathway as potential predictive markers for radiation-induced esophagitis and pneumonitis. We genotyped 440 SNPs from 45 genes in DSB repair pathways in 250 stage I–III NSCLC patients who received definitive radiation or chemoradiation therapy, followed by internal validation in 170 additional patients. We found that 11 SNPs for esophagitis and 8 SNPs for pneumonitis showed consistent effects between discovery and validation populations (same direction of OR and reached significance in meta-analysis). Among them, rs7165790 in the BLM gene was significantly associated with decreased risk of esophagitis in both discovery (OR = 0.59, 95% CI: 0.37–0.97, p = 0.037) and validation subgroups (OR = 0.45, 95% CI: 0.22–0.94, p = 0.032). A strong cumulative effect was observed for the top SNPs, and gene-based tests revealed 12 genes significantly associated with esophagitis or pneumonitis. Our results support the notion that genetic variations within DSB repair pathway could influence the risk of developing toxicities following definitive RT in NSCLC. PMID:26901225

  14. [Acute myocarditis].

    PubMed

    Combes, Alain

    2012-06-01

    Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Acute myocarditis must be considered in patients who present with recent-onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackievirus and adenovirus being the most frequently viruses responsible for the disease. Treatment of myocarditis remains largely supportive, since immunosuppression has not been proven to be beneficial for acute lymphocytic myocarditis. Trials of antiviral therapies, or immunostimulants such as interferons, suggest a potential therapeutic role but require further investigation. Lastly, early recognition of patients rapidly progressing to refractory cardiac failure and their immediate transfer to a medical-surgical center experienced in mechanical circulatory support is warranted. In this setting, ECMO should be the first-line mechanical assistance. For highly unstable patients, a Mobile Cardiac Assistance Unit, that rapidly travels to primary care hospitals with a portable ECMO system and hooks it up before refractory multiorgan failure takes hold, is the preferred option. PMID:22515999

  15. [Acute myocarditis].

    PubMed

    Combes, Alain

    2013-05-01

    Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Acute myocarditis must be considered in patients who present with recent onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackievirus and adenovirus being the most frequently viruses responsible for the disease. Treatment of myocarditis remains largely supportive, since immunosuppression has not been proven to be beneficial for acute lymphocytic myocarditis. Trials of antiviral therapies, or immunostimulants such as interferons, suggest a potential therapeutic role but require further investigation. Lastly, early recognition of patients rapidly progressing to refractory cardiac failure and their immediate transfer to a medical-surgical center experienced in mechanical circulatory support is warranted. In this setting, ECMO should be the first-line mechanical assistance. For highly unstable patients, a Mobile Cardiac Assistance Unit, that rapidly travels to primary care hospitals with a portable ECMO system and hooks it up before refractory multiorgan failure takes hold, is the preferred option. PMID:23789482

  16. A Case of Acute Generalized Pustular Psoriasis of von Zumbusch Triggered by Hypocalcemia

    PubMed Central

    Guerreiro de Moura, Carlos Antônio Gusmão; de Assis, Luiz Henrique; Góes, Paulo; Rosa, Fabiana; Nunes, Victor; Gusmão, Ítalo Magalhães; Cruz, Constança Margarida Sampaio

    2015-01-01

    Psoriasis is an autoimmune disease triggered by different conditions in genetically susceptible people. It is characterized by variable cutaneous manifestations including localized or disseminated pustules. Generalized pustular psoriasis (GPP) has two main clinical forms: von Zumbusch psoriasis, characterized by severe erythrodermia and scaling skin after the resolution of pustules, and the annular form. GPP may also present severe extracutaneous manifestations including pneumonitis, heart failure and hepatitis. Old reports showed a relationship between hypoparathyroidism and hypocalcemia as triggers for GPP highlighting the importance of adequate workup of the patient and possible therapeutic changes in acute situations. Here, we present a case of severe von Zumbusch psoriasis with life-threatening complications triggered by severe hypocalcemia secondary to hypoparathyroidism successfully treated with aggressive calcium reposition. PMID:26955330

  17. Bone marrow transplantation for acute myelogenous leukemia: factors associated with early mortality

    SciTech Connect

    Bortin, M.M.; Gale, R.P.; Kay, H.E.; Rimm, A.A.

    1983-03-04

    Comprehensive data were reported to the International Bone Marrow Transplant Registry, Milwaukee, regarding 156 patients with acute myelogenous leukemia who were treated with allogeneic bone marrow transplantation between 1978 and 1980. The minimum observation period was 15 months after transplant and most deaths occurred within the first six months. Prognostic factors were evaluated for associations with early mortality or life-threatening complications. Most early deaths were due to infections, interstitial pneumonitis, and graft-v-host disease (GVHD). Multivariate analyses disclosed five factors with significant associations with early death or a major cause of early death: (1) disease status; (2) dose-rate of irradiation; (3) drug used to prevent GVHD; (4) severity of GVHD; and (5) dose of marrow cells.It is emphasized that several of the important prognostic factors are within the control of the referring physician or the transplant team.

  18. Acute cerebellar ataxia

    MedlinePlus

    Cerebellar ataxia; Ataxia - acute cerebellar; Cerebellitis; Post-varicella acute cerebellar ataxia; PVACA ... Acute cerebellar ataxia in children, especially younger than age 3, may occur several weeks after an illness caused by a virus. ...

  19. Ear infection - acute

    MedlinePlus

    Otitis media - acute; Infection - inner ear; Middle ear infection - acute ... Casselbrandt ML, Mandel EM. Acute otitis media and otitis media with effusion. In: Flint PW, Haughey BH, Lund V, et al, eds. Cummings Otolaryngology: Head & Neck Surgery . 6th ed. ...

  20. Electrophiles and acute toxicity to fish.

    PubMed Central

    Hermens, J L

    1990-01-01

    Effect concentrations in fish LC50 tests with directly acting electrophiles are lower than those of unreactive chemicals that act by narcosis. LC50 values of more hydrophobic reactive chemicals tend to approach those of unreactive chemicals. Quantitative studies to correlate fish LC50 data to physical-chemical properties indicate that LC50 values of reactive chemicals depend on hydrophobicity as well as chemical reactivity. In this paper, several examples will be given of chemical structures that are known as direct electrophiles. This classification might be useful to identify chemicals that are more effective at lower concentrations than unreactive compounds. Chemicals that require bioactivation are not included because almost no information is available on the influence of bioactivation on acute toxic effects in aquatic organisms. PMID:2269228

  1. Isocyanate exposure and hypersensitivity pneumonitis--report of a probable case and prevalence of specific immunoglobulin G antibodies among exposed individuals.

    PubMed

    Seldén, A I; Belin, L; Wass, U

    1989-06-01

    A car painter experienced three episodes of a hypersensitivity pneumonitis-like disease after exposure to two-component acrylic lacquers with hexamethylene diisocyanate (HDI) as the curing agent. High titers of HDI-specific immunoglobulin (Ig) G antibodies were found in the patient's serum by means of enzyme-linked immunosorbent assay (ELISA). In the ELISA, 5 to 10% of the sera from 455 isocyanate-exposed but asymptomatic workers were positive, depending on the criterion used for a positive test, whereas 0% of the sera from 157 unexposed referents was found to be positive. Among 10 subjects with isocyanate-induced asthma and isocyanate-specific IgE antibodies, 50% had specific IgG. It was concluded that the presence of isocyanate-specific IgG antibodies in serum is correlated with isocyanate exposure rather than with symptoms of isocyanate-induced disease. PMID:2781254

  2. Acute pain.

    PubMed

    Good, M

    1999-01-01

    The review of acute pain describes the problem of unresolved pain and its effects on the neural, autonomic, and immune systems. Conceptualizations and mechanisms of pain are reviewed as well as theories of pain management. Descriptive studies of patient and nurse factors that inhibit effective pain management are discussed, followed by studies of pharmacological and nonpharmacological interventions. Critical analysis reveals that most studies were atheoretical, and therefore, this proliferation of information lacked conceptual coherence and organization. Furthermore, the nature and extent of barriers to pain management were described, but few intervention studies have been devised, as yet, to modify the knowledge, beliefs, and attitudes of nurses and patients that are barriers to pain management. Although some of the complementary therapies have sufficient research support to be used in clinical pain management, the physiological mechanisms and outcomes need to be studied. It is critical at this time to design studies of interventions to improve assessment, decision making, attentive care, and patient teaching. PMID:10418655

  3. [Imaging in acute toxic encephalopathy].

    PubMed

    Dietemann, J-L; Botelho, C; Nogueira, T; Vargas, M I; Audibert, C; Abu Eid, M; Bogorin, A; Bernardo, R; Jacques, C; Kremer, S; Zöllner, G

    2004-09-01

    Neuroimaging, particularly MR imaging, plays a major role for the diagnosis of many acute toxic encephalopathies. Toxic disorders are related to drugs (immunosuppressive agents, chemotherapeutic agents, anti-epileptic drugs, heroin...), to metals (lead, manganese, mercury...), and to industrial and environmental chemicals (solvent, carbon monoxide...). MR imaging with diffusion and perfusion imaging provides information regarding brain lesions induced by the toxic agents (vasogenic edema, cytotoxic edema, infarction, hemorrhage, demyelination...). PMID:15545943

  4. Clinical and Dosimetric Predictors of Radiation Pneumonitis in a Large Series of Patients Treated With Stereotactic Body Radiation Therapy to the Lung

    SciTech Connect

    Baker, Ryan; Han Gang; Sarangkasiri, Siriporn; DeMarco, MaryLou; Turke, Carolyn; Stevens, Craig W.; Dilling, Thomas J.

    2013-01-01

    Purpose: To report clinical and dosimetric factors predictive of radiation pneumonitis (RP) in patients receiving lung stereotactic body radiation therapy (SBRT) from a series of 240 patients. Methods and Materials: Of the 297 isocenters treating 263 patients, 240 patients (n=263 isocenters) had evaluable information regarding RP. Age, gender, current smoking status and pack-years, O{sub 2} use, Charlson Comorbidity Index, prior lung radiation therapy (yes/no), dose/fractionation, V{sub 5}, V{sub 13}, V{sub 20}, V{sub prescription}, mean lung dose, planning target volume (PTV), total lung volume, and PTV/lung volume ratio were recorded. Results: Twenty-nine patients (11.0%) developed symptomatic pneumonitis (26 grade 2, 3 grade 3). The mean V{sub 20} was 6.5% (range, 0.4%-20.2%), and the average mean lung dose was 5.03 Gy (0.547-12.2 Gy). In univariable analysis female gender (P=.0257) and Charlson Comorbidity index (P=.0366) were significantly predictive of RP. Among dosimetric parameters, V{sub 5} (P=.0186), V{sub 13} (P=.0438), and V{sub prescription} (where dose = 60 Gy) (P=.0128) were significant. There was only a trend toward significance for V{sub 20} (P=.0610). Planning target volume/normal lung volume ratio was highly significant (P=.0024). In multivariable analysis the clinical factors of female gender, pack-years smoking, and larger gross internal tumor volume and PTV were predictive (P=.0094, .0312, .0364, and .052, respectively), but no dosimetric factors were significant. Conclusions: Rate of symptomatic RP was 11%. Our mean lung dose was <600 cGy in most cases and V20 <10%. In univariable analysis, dosimetric factors were predictive, while tumor size (or tumor/lung volume ratio) played a role in multivariable and univariable and analysis, respectively.

  5. Bone marrow transplantation alters lung antigen presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection

    PubMed Central

    Zhou, Xiaofeng; Loomis-King, Hillary; Gurczynski, Stephen J.; Wilke, Carol A.; Konopka, Kristine E.; Ptaschinski, Catherine; Coomes, Stephanie M; Iwakura, Yoichiro; van Dyk, Linda F.; Lukacs, Nicholas W.; Moore, Bethany B.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplant (BMT) followed by infection with murine gamma herpesvirus (γHV-68) that results in pneumonitis and fibrosis and mimics human “non-infectious” HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection (dpi). CD4 T cells in BMT mice are skewed towards IL-17A rather than IFN-γ production. Transplantation of bone marrow from Il-17a−/− donors or treatment with anti-IL-17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more TGF-β1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-γ but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non-BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest “non-infectious” HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset. PMID:26376362

  6. A Yersinia pestis tat Mutant Is Attenuated in Bubonic and Small-Aerosol Pneumonic Challenge Models of Infection but Not As Attenuated by Intranasal Challenge

    PubMed Central

    Bozue, Joel; Cote, Christopher K.; Chance, Taylor; Kugelman, Jeffrey; Kern, Steven J.; Kijek, Todd K.; Jenkins, Amy; Mou, Sherry; Moody, Krishna; Fritz, David; Robinson, Camenzind G.; Bell, Todd; Worsham, Patricia

    2014-01-01

    Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge. PMID:25101850

  7. Distribution of the ompA-types among ruminant and swine pneumonic strains of Pasteurella multocida exhibiting various cap-locus and toxA patterns.

    PubMed

    Vougidou, C; Sandalakis, V; Psaroulaki, A; Siarkou, V; Petridou, E; Ekateriniadou, L

    2015-05-01

    Pasteurella multocida is an important pathogen in food-producing animals and numerous virulence genes have been identified in an attempt to elucidate the pathogenesis of pasteurellosis. Currently, some of these genes including the capsule biosynthesis genes, the toxA and the OMPs-encoding genes have been suggested as epidemiological markers. However, the number of studies concerning ruminant isolates is limited, while, no attempt has ever been made to investigate the existence of ompA sequence diversity among P. multocida isolates. The aim of the present study was the comparative analysis of 144 P. multocida pneumonic isolates obtained from sheep, goats, cattle and pigs by determining the distribution of the ompA-types in conjunction with the cap-locus and toxA patterns. The ompA genotypes of the isolates were determined using both a PCR-RFLP method and DNA sequence analysis. The most prevalent capsule biosynthesis gene among the isolates was capA (86.1%); a noticeable, however, rate of capD-positive isolates (38.6%) was found among the ovine isolates that had been associated primarily with the capsule type A in the past. Moreover, an unexpectedly high percentage of toxA-positive pneumonic isolates was noticed among small ruminants (93.2% and 85.7% in sheep and goats, respectively), indicating an important epidemiological role of toxigenic P. multocida for these species. Despite their great heterogeneity, certain ompA-genotypes were associated with specific host species, showing evidence of a host preference. The OmpA-based PCR-RFLP method developed proved to be a valuable tool in typing P. multocida strains. PMID:25946323

  8. Acute Inhalation Injury

    PubMed Central

    Gorguner, Metin; Akgun, Metin

    2010-01-01

    Inhaled substances may cause injury in pulmonary epithelium at various levels of respiratory tract, leading from simple symptoms to severe disease. Acute inhalation injury (AII) is not uncommon condition. There are certain high risk groups but AII may occur at various places including home or workplace. Environmental exposure is also possible. In addition to individual susceptibility, the characteristics of inhaled substances such as water solubility, size of substances and chemical properties may affect disease severity as well as its location. Although AII cases may recover in a few days but AII may cause long-term complications, even death. We aimed to discuss the effects of short-term exposures (minutes to hours) to toxic substances on the lungs. PMID:25610115

  9. Exploring waiving opportunities for mammalian acute systemic toxicity tests.

    PubMed

    Graepel, Rabea; Asturiol, David; Prieto, Pilar; Worth, Andrew P

    2016-07-01

    A survey was carried out to explore opportunities for waiving mammalian acute systemic toxicity tests. We were interested in finding out whether data from a sub-acute toxicity test could be used to predict the outcome of an acute systemic toxicity test. The survey was directed at experts in the field of toxicity testing, and was carried out in the context of the upcoming 2018 final registration deadline for chemicals under the EU REACH Regulation. In addition to the survey, a retrospective data analysis of chemicals that had already been registered with the European Chemicals Agency, and for which both acute and sub-acute toxicity data were available, was carried out. This data analysis was focused on chemicals that were administered via the oral route. The answers to the questionnaire showed a willingness to adopt waiving opportunities. In addition, the responses showed that data from a sub-acute toxicity test or dose-range finding study might be useful for predicting chemicals that do not require classification for acute oral toxicity (LD50 > 2000mg/kg body weight). However, with the exception of substances that fall into the non-classified category, it is difficult to predict current acute oral toxicity categories. PMID:27494626

  10. Chemical crowd control agents.

    PubMed

    Menezes, Ritesh G; Hussain, Syed Ather; Rameez, Mansoor Ali Merchant; Kharoshah, Magdy A; Madadin, Mohammed; Anwar, Naureen; Senthilkumaran, Subramanian

    2016-03-01

    Chemical crowd control agents are also referred to as riot control agents and are mainly used by civil authorities and government agencies to curtail civil disobedience gatherings or processions by large crowds. Common riot control agents used to disperse large numbers of individuals into smaller, less destructive, and more easily controllable numbers include chloroacetophenone, chlorobenzylidenemalononitrile, dibenzoxazepine, diphenylaminearsine, and oleoresin capsicum. In this paper, we discuss the emergency medical care needed by sufferers of acute chemical agent contamination and raise important issues concerning toxicology, safety and health. PMID:26658556

  11. Chemical Emergencies

    MedlinePlus

    When a hazardous chemical has been released, it may harm people's health. Chemical releases can be unintentional, as in the case of an ... the case of a terrorist attack with a chemical weapon. Some hazardous chemicals have been developed by ...

  12. Acute oral, dermal, and inhalation studies.

    PubMed

    Thomann, P; Krüger, L

    1975-01-01

    By appropriate testing procedures, it has been demonstrated that the compounds used as fluorescent whitening agents (FWAs) have a very low order of systemic toxicity in acute experiments. No evidence of dermal toxicity has been found. The full chemical names of the fluorescent whitening agents (FWAs) investigated in this study are listed below. They have been numbered for easy identification and classified by chemical groups. PMID:1064537

  13. Pneumomediastinum, subcutaneous emphysema, and pneumothorax after a pulmonary function testing in a patient with bleomycin-induced interstitial pneumonitis*

    PubMed Central

    Araujo, Mariana Sponholz; Fernandes, Frederico Leon Arrabal; Kay, Fernando Uliana; Carvalho, Carlos Roberto Ribeiro

    2013-01-01

    Spontaneous pneumomediastinum is an uncommon event, the clinical picture of which includes retrosternal chest pain, subcutaneous emphysema, dyspnea, and dysphonia. The pathophysiological mechanism involved is the emergence of a pressure gradient between the alveoli and surrounding structures, causing alveolar rupture with subsequent dissection of the peribronchovascular sheath and infiltration of the mediastinum and subcutaneous tissue with air. Known triggers include acute exacerbations of asthma and situations that require the Valsalva maneuver. We described and documented with HRCT scans the occurrence of pneumomediastinum after a patient with bleomycin-induced interstitial lung disease underwent pulmonary function testing. Although uncommon, the association between pulmonary function testing and air leak syndromes has been increasingly reported in the literature, and lung diseases, such as interstitial lung diseases, include structural changes that facilitate the occurrence of this complication. PMID:24310635

  14. Acute toxicity of gasoline and some additives

    SciTech Connect

    Reese, E.; Kimbrough, R.D.

    1993-12-01

    The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels. 128 refs., 7 tabs.

  15. Acute toxicity of gasoline and some additives.

    PubMed Central

    Reese, E; Kimbrough, R D

    1993-01-01

    The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels. PMID:8020435

  16. Acute kidney failure

    MedlinePlus

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  17. Acute arterial occlusion - kidney

    MedlinePlus

    Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... kidneys need a good blood supply. The main artery to the kidney is called the renal artery. ...

  18. Acute arterial occlusion - kidney

    MedlinePlus

    ... arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... often result in permanent kidney failure. Acute arterial occlusion of the renal artery can occur after injury ...

  19. Acute Lymphocytic Leukemia

    MedlinePlus

    ... hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too ... of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in ...

  20. Stereotactic body radiotherapy for Stage I lung cancer with chronic obstructive pulmonary disease: special reference to survival and radiation-induced pneumonitis

    PubMed Central

    Inoue, Toshihiko; Shiomi, Hiroya; Oh, Ryoong-Jin

    2015-01-01

    This retrospective study aimed to evaluate radiation-induced pneumonitis (RIP) and a related condition that we define in this report—prolonged minimal RIP (pmRIP)—after stereotactic body radiotherapy (SBRT) for Stage I primary lung cancer in patients with chronic obstructive pulmonary disease (COPD). We assessed 136 Stage I lung cancer patients with COPD who underwent SBRT. Airflow limitation on spirometry was classified into four Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, with minor modifications: GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe) and GOLD 4 (very severe). On this basis, we defined two subgroups: COPD-free (COPD −) and COPD-positive (COPD +). There was no significant difference in overall survival or cause-specific–survival between these groups. Of the 136 patients, 44 (32%) had pmRIP. Multivariate analysis showed that COPD and the Brinkman index were statistically significant risk factors for the development of pmRIP. COPD and the Brinkman index were predictive factors for pmRIP, although our findings also indicate that SBRT can be tolerated in early lung cancer patients with COPD. PMID:25887042

  1. A rare association of localized scleroderma type morphea, vitiligo, autoimmune hypothyroidism, pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case report

    PubMed Central

    2012-01-01

    Background The localized scleroderma (LS) known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our knowledge this is the first case of a morphea forming part of a multiple autoimmune syndrome (MAS) and presenting simultaneously with autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case presentation We report an uncommon case of a white 53 year old female patient with LS as part of a multiple autoimmune syndrome associated with pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis presenting a favorable response with thrombopoietin receptor agonists, pulses of methylprednisolone and cyclophosphamide. Conclusion Is likely that LS have an autoimmune origin and in this case becomes part of MAS, which consist on the presence of three or more well-defined autoimmune diseases in a single patient. PMID:23256875

  2. Redox-Triggered Release of Moxifloxacin from Mesoporous Silica Nanoparticles Functionalized with Disulfide Snap-Tops Enhances Efficacy Against Pneumonic Tularemia in Mice.

    PubMed

    Lee, Bai-Yu; Li, Zilu; Clemens, Daniel L; Dillon, Barbara Jane; Hwang, Angela A; Zink, Jeffrey I; Horwitz, Marcus A

    2016-07-01

    Effective and rapid treatment of tularemia is needed to reduce morbidity and mortality of this potentially fatal infectious disease. The etiologic agent, Francisella tularensis, is a facultative intracellular bacterial pathogen which infects and multiplies to high numbers in macrophages. Nanotherapeutics are particularly promising for treatment of infectious diseases caused by intracellular pathogens, whose primary host cells are macrophages, because nanoparticles preferentially target and are avidly internalized by macrophages. A mesoporous silica nanoparticle (MSN) has been developed functionalized with disulfide snap-tops that has high drug loading and selectively releases drug intracellularly in response to the redox potential. These nanoparticles, when loaded with Hoechst fluorescent dye, release their cargo exclusively intracellularly and stain the nuclei of macrophages. The MSNs loaded with moxifloxacin kill F. tularensis in macrophages in a dose-dependent fashion. In a mouse model of lethal pneumonic tularemia, MSNs loaded with moxifloxacin prevent weight loss, illness, and death, markedly reduce the burden of F. tularensis in the lung, liver, and spleen, and are significantly more efficacious than an equivalent amount of free drug. An important proof-of-principle for the potential therapeutic use of a novel nanoparticle drug delivery platform for the treatment of infectious diseases is provided. PMID:27246117

  3. Correlation between imaging features of Pneumocystis Jiroveci Pneumonitis (PCP), CD4+ T lymphocyte count, and plasma HIV viral load: A study in 50 consecutive AIDS patients

    PubMed Central

    Deng, Ying-Ying; Liu, Shui-Teng; Liu, Yan; Liu, Ying-Xia; Wang, Yi-Xiang J; Zhu, Wen-Ke; Le, Xiao-Hua; Yu, Wei-Ye; Zhou, Bo-Ping

    2012-01-01

    Purpose To investigate the imaging manifestations of Pneumocystis Jiroveci Pneumonitis (PCP) in AIDS patients, and the correlation between imaging features, CD4+ lymphocyte count, and plasma HIV viral load. Materials and methods A total of consecutive 50 AIDS patients with PCP were reviewed retrospectively. Chest CT manifestations, CD4+ lymphocyte count, and plasma HIV viral load were analyzed to investigate their correlation. Results PCP chest CT manifestations included ground-glass opacities dominated in 28 cases (28/50, 56%), lung cysts dominated in 10 cases (10/50, 20%), consolidation dominated in 6 cases (6/50, 12%), interstitial lesion dominated in 3 cases (3/50, 6%), and mixed lesions in 3 cases (3/50, 6%). In these 50 patients, CD4+ lymphocyte count ranged from 2 to 373 cells/µL. Plasma HIV viral load ranged from 500 to 5.28×107 copies/mL. CD4+ lymphocyte count in ground-glass opacities dominated patients was higher than that of lung cyst dominated patients (P<0.05). Plasma virus load of lung cysts dominated PCP patients was higher than that of consolidation dominated patients (P<0.05). Conclusions The typical chest imaging features of PCP in AIDS patients included lung ground-glass opacities and lung cysts. The chest imaging features were correlated with CD4+ T lymphocyte count and plasma HIV viral load. PMID:23256070

  4. Association of P53 and ATM Polymorphisms With Risk of Radiation-Induced Pneumonitis in Lung Cancer Patients Treated With Radiotherapy

    SciTech Connect

    Yang Ming; Zhang Li; Bi Nan; Ji Wei; Tan Wen; Zhao Lujun; Yu Dianke; Wu Chen; Wang Luhua

    2011-04-01

    Purpose: Radiation-induced pneumonitis (RP) is the most common dose-limiting complication in lung cancer patients treated with radiotherapy. Accumulating evidence indicates that P53 and the ataxia telangiectasia-mutated protein (ATM)-dependent signaling response cascade play a crucial role in radiation-induced diseases. Consistent with this, our previous study showed that a functional genetic ATM polymorphism was associated with increased RP risk. Methods and Materials: To evaluate the role of genetic P53 polymorphism in RP, we analyzed the P53 Arg72Pro polymorphism in a cohort including 253 lung cancer patients receiving thoracic irradiation. Results: We found that the P53 72Arg/Arg genotype was associated with increased RP risk compared with the 72Pro/Pro genotype. Furthermore, the P53 Arg72Pro and ATM -111G>A polymorphisms display an additive combination effect in intensifying the risk of developing RP. The cross-validation test showed that 63.2% of RP cases can be identified by P53 and ATM genotypes. Conclusions: These results indicate that genetic polymorphisms in the ATM-P53 pathway influence susceptibility to RP and genotyping P53 and ATM polymorphisms might help to identify patients susceptible to developing RP when receiving radiotherapy.

  5. Regulatory T Cells Contribute to the Inhibition of Radiation-Induced Acute Lung Inflammation via Bee Venom Phospholipase A2 in Mice

    PubMed Central

    Shin, Dasom; Lee, Gihyun; Sohn, Sung-Hwa; Park, Soojin; Jung, Kyung-Hwa; Lee, Ji Min; Yang, Jieun; Cho, Jaeho; Bae, Hyunsu

    2016-01-01

    Bee venom has long been used to treat various inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. Previously, we reported that bee venom phospholipase A2 (bvPLA2) has an anti-inflammatory effect through the induction of regulatory T cells. Radiotherapy is a common anti-cancer method, but often causes adverse effects, such as inflammation. This study was conducted to evaluate the protective effects of bvPLA2 in radiation-induced acute lung inflammation. Mice were focally irradiated with 75 Gy of X-rays in the lung and administered bvPLA2 six times after radiation. To evaluate the level of inflammation, the number of immune cells, mRNA level of inflammatory cytokine, and histological changes in the lung were measured. BvPLA2 treatment reduced the accumulation of immune cells, such as macrophages, neutrophils, lymphocytes, and eosinophils. In addition, bvPLA2 treatment decreased inflammasome-, chemokine-, cytokine- and fibrosis-related genes’ mRNA expression. The histological results also demonstrated the attenuating effect of bvPLA2 on radiation-induced lung inflammation. Furthermore, regulatory T cell depletion abolished the therapeutic effects of bvPLA2 in radiation-induced pneumonitis, implicating the anti-inflammatory effects of bvPLA2 are dependent upon regulatory T cells. These results support the therapeutic potential of bvPLA2 in radiation pneumonitis and fibrosis treatments. PMID:27144583

  6. Regulatory T Cells Contribute to the Inhibition of Radiation-Induced Acute Lung Inflammation via Bee Venom Phospholipase A₂ in Mice.

    PubMed

    Shin, Dasom; Lee, Gihyun; Sohn, Sung-Hwa; Park, Soojin; Jung, Kyung-Hwa; Lee, Ji Min; Yang, Jieun; Cho, Jaeho; Bae, Hyunsu

    2016-01-01

    Bee venom has long been used to treat various inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. Previously, we reported that bee venom phospholipase A₂ (bvPLA₂) has an anti-inflammatory effect through the induction of regulatory T cells. Radiotherapy is a common anti-cancer method, but often causes adverse effects, such as inflammation. This study was conducted to evaluate the protective effects of bvPLA₂ in radiation-induced acute lung inflammation. Mice were focally irradiated with 75 Gy of X-rays in the lung and administered bvPLA₂ six times after radiation. To evaluate the level of inflammation, the number of immune cells, mRNA level of inflammatory cytokine, and histological changes in the lung were measured. BvPLA₂ treatment reduced the accumulation of immune cells, such as macrophages, neutrophils, lymphocytes, and eosinophils. In addition, bvPLA₂ treatment decreased inflammasome-, chemokine-, cytokine- and fibrosis-related genes' mRNA expression. The histological results also demonstrated the attenuating effect of bvPLA₂ on radiation-induced lung inflammation. Furthermore, regulatory T cell depletion abolished the therapeutic effects of bvPLA₂ in radiation-induced pneumonitis, implicating the anti-inflammatory effects of bvPLA₂ are dependent upon regulatory T cells. These results support the therapeutic potential of bvPLA₂ in radiation pneumonitis and fibrosis treatments. PMID:27144583

  7. Imaging of Acute Pancreatitis.

    PubMed

    Thoeni, Ruedi F

    2015-11-01

    Acute pancreatitis is an acute inflammation of the pancreas. Several classification systems have been used in the past but were considered unsatisfactory. A revised Atlanta classification of acute pancreatitis was published that assessed the clinical course and severity of disease; divided acute pancreatitis into interstitial edematous pancreatitis and necrotizing pancreatitis; discerned an early phase (first week) from a late phase (after the first week); and focused on systemic inflammatory response syndrome and organ failure. This article focuses on the revised classification of acute pancreatitis, with emphasis on imaging features, particularly on newly-termed fluid collections and implications for the radiologist. PMID:26526433

  8. Acute loss of consciousness.

    PubMed

    Tristán, Bekinschtein; Gleichgerrcht, Ezequiel; Manes, Facundo

    2015-01-01

    Acute loss of consciousness poses a fascinating scenario for theoretical and clinical research. This chapter introduces a simple yet powerful framework to investigate altered states of consciousness. We then explore the different disorders of consciousness that result from acute brain injury, and techniques used in the acute phase to predict clinical outcome in different patient populations in light of models of acute loss of consciousness. We further delve into post-traumatic amnesia as a model for predicting cognitive sequels following acute loss of consciousness. We approach the study of acute loss of consciousness from a theoretical and clinical perspective to conclude that clinicians in acute care centers must incorporate new measurements and techniques besides the classic coma scales in order to assess their patients with loss of consciousness. PMID:25702218

  9. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  10. Acute chylous peritonitis due to acute pancreatitis.

    PubMed

    Georgiou, Georgios K; Harissis, Haralampos; Mitsis, Michalis; Batsis, Haralampos; Fatouros, Michalis

    2012-04-28

    We report a case of acute chylous ascites formation presenting as peritonitis (acute chylous peritonitis) in a patient suffering from acute pancreatitis due to hypertriglyceridemia and alcohol abuse. The development of chylous ascites is usually a chronic process mostly involving malignancy, trauma or surgery, and symptoms arise as a result of progressive abdominal distention. However, when accumulation of "chyle" occurs rapidly, the patient may present with signs of peritonitis. Preoperative diagnosis is difficult since the clinical picture usually suggests hollow organ perforation, appendicitis or visceral ischemia. Less than 100 cases of acute chylous peritonitis have been reported. Pancreatitis is a rare cause of chyloperitoneum and in almost all of the cases chylous ascites is discovered some days (or even weeks) after the onset of symptoms of pancreatitis. This is the second case in the literature where the patient presented with acute chylous peritonitis due to acute pancreatitis, and the presence of chyle within the abdominal cavity was discovered simultaneously with the establishment of the diagnosis of pancreatitis. The patient underwent an exploratory laparotomy for suspected perforated duodenal ulcer, since, due to hypertriglyceridemia, serum amylase values appeared within the normal range. Moreover, abdominal computed tomography imaging was not diagnostic for pancreatitis. Following abdominal lavage and drainage, the patient was successfully treated with total parenteral nutrition and octreotide. PMID:22563182

  11. Acute toxicity of trichloroethylene to saltwater organisms

    SciTech Connect

    Ward, G.S.; Tolmsoff, A.J.; Petrocelli, S.R.

    1986-12-01

    Trichloroethylene (TCE) is a chlorinated aliphatic hydrocarbon primarily utilized for vapor-phase degreasing in the fabricated metals industry. Other applications include cold-metal cleaning and use in the manufacture of organic chemicals. TCE enters the environment as a result of volatilization during its production and through its industrial uses. TCE has been detected in aquatic environments and organisms at part-per-trillion (pptr) concentrations. Although TCE is indicated to be widely distributed, relatively limited data exist on the acute effects of TCE on aquatic organisms, especially saltwater species. Results of static acute tests of TCE with a saltwater alga, invertebrate, and fish are reported here to enhance the data base.

  12. In Vivo Nanodetoxication for Acute Uranium Exposure.

    PubMed

    Guzmán, Luis; Durán-Lara, Esteban F; Donoso, Wendy; Nachtigall, Fabiane M; Santos, Leonardo S

    2015-01-01

    Accidental exposure to uranium is a matter of concern, as U(VI) is nephrotoxic in both human and animal models, and its toxicity is associated to chemical toxicity instead of radioactivity. We synthesized different PAMAM G4 and G5 derivatives in order to prove their interaction with uranium and their effect on the viability of red blood cells in vitro. Furthermore, we prove the effectiveness of the selected dendrimers in an animal model of acute uranium intoxication. The dendrimer PAMAM G4-Lys-Fmoc-Cbz demonstrated the ability to chelate the uranyl ion in vivo, improving the biochemical and histopathologic features caused by acute intoxication with uranium. PMID:26083036

  13. Towards Development of an Edible Vaccine against Bovine Pneumonic Pasteurellosis Using Transgenic White Clover Expressing a Mannheimia haemolytica A1 Leukotoxin 50 Fusion Protein

    PubMed Central

    Lee, Raymond W. H.; Strommer, Judith; Hodgins, Doug; Shewen, Patricia E.; Niu, Yongqing; Lo, Reggie Y. C.

    2001-01-01

    Development of vaccines against bovine pneumonia pasteurellosis, or shipping fever, has focused mainly on Mannheimia haemolytica A1 leukotoxin (Lkt). In this study, the feasibility of expressing Lkt in a forage plant for use as an edible vaccine was investigated. Derivatives of the M. haemolytica Lkt in which the hydrophobic transmembrane domains were removed were made. Lkt66 retained its immunogenicity and was capable of eliciting an antibody response in rabbits that recognized and neutralized authentic Lkt. Genes encoding a shorter Lkt derivative, Lkt50, fused to a modified green fluorescent protein (mGFP5), were constructed for plant transformation. Constructs were screened by Western immunoblot analysis for their ability to express the fusion protein after agroinfiltration in tobacco. The fusion construct pBlkt50-mgfp5, which employs the cauliflower mosaic virus 35S promoter for transcription, was selected and introduced into white clover by Agrobacterium tumefaciens-mediated transformation. Transgenic lines of white clover were recovered, and expression of Lkt50-GFP was monitored and confirmed by laser confocal microscopy and Western immunoblot analysis. Lkt50-GFP was found to be stable in clover tissue after drying of the plant material at room temperature for 4 days. An extract containing Lkt50-GFP from white clover was able to induce an immune response in rabbits (via injection), and rabbit antisera recognized and neutralized authentic Lkt. This is the first demonstration of the expression of an M. haemolytica antigen in plants and paves the way for the development of transgenic plants expressing M. haemolytica antigens as an edible vaccine against bovine pneumonic pasteurellosis. PMID:11500456

  14. Pre–radiation Therapy Fluorine 18 Fluorodeoxyglucose PeT helps identify Patients with esophageal cancer at high risk for radiation Pneumonitis1

    PubMed Central

    Castillo, Richard; Pham, Ngoc; Castillo, Edward; Aso-Gonzalez, Samantha; Ansari, Sobiya; Hobbs, Brian; Palacio, Diana; Skinner, Heath; Guerrero, Thomas M.

    2015-01-01

    Purpose To examine the association between pre–radiation therapy (RT) fluorine 18 fluorodeoxyglucose (FDG) uptake and post-RT symptomatic radiation pneumonitis (RP). Materials and Methods In accordance with the retrospective study protocol approved by the institutional review board, 228 esophageal cancer patients who underwent FDG PET/CT before chemotherapy and RT were examined. RP symptoms were evaluated by using the Common Terminology Criteria for Adverse Events, version 4.0, from the consensus of five clinicians. By using the cumulative distribution of standardized uptake values (SUVs) within the lungs, those values greater than 80%–95% of the total lung voxels were determined for each patient. The effect of pre-chemotherapy and RT FDG uptake, dose, and patient or treatment characteristics on RP toxicity was studied by using logistic regression. Results The study subjects were treated with three-dimensional conformal RT (n = 36), intensity-modulated RT (n = 135), or proton therapy (n = 57). Logistic regression analysis demonstrated elevated FDG uptake at pre-chemotherapy and RT was related to expression of RP symptoms. Study subjects with elevated 95% percentile of the SUV (SUV95) were more likely to develop symptomatic RP (P .000012); each 0.1 unit increase in SUV95 was associated with a 1.36-fold increase in the odds of symptomatic RP. Receiver operating characteristic (ROC) curve analysis resulted in area under the ROC curve of 0.676 (95% confidence interval: 0.58, 0.77), sensitivity of 60%, and specificity of 71% at the 1.17 SUV95 threshold. CT imaging and dosimetric parameters were found to be poor predictors of RP symptoms. Conclusion The SUV95, a biomarker of pretreatment pulmonary metabolic activity, was shown to be prognostic of symptomatic RP. Elevation in this pretreatment biomarker identifies patients at high risk for posttreatment symptomatic RP. PMID:25584706

  15. Role of type II pneumocytes in pathogenesis of radiation pneumonitis: dose response of radiation-induced lung changes in the transient high vascular permeability period.

    PubMed

    Osterreicher, Jan; Pejchal, Jaroslav; Skopek, Jirí; Mokrỳ, Jaroslav; Vilasová, Zdena; Psutka, Jan; Vávrová, Jirina; Mazurová, Yvona

    2004-12-01

    We studied the dose response of pulmonary changes at 3 weeks after 1-25 Gy irradiation and we investigated the effects of an anti-inflammatory drug. Wistar rats were given a single dose of 1-25Gy irradiation to the thorax. Group one was treated with saline only, while group two was administered subcutaneously a combination of pentoxifylline (35 mg/kg) and dexamethasone (1 mg/kg) twice per week. Lungs were examined histochemically and number of neutrophile granulocytes, alveolar septal thickness, air/tissue ratio, number of alveoli per field, number of type II pneumocytes per alveolus, and occludin 1 expression were measured. A significant dose-dependent depletion of type II pneumocytes was found after irradiation with a dose of 1 Gy and higher. Alveolar neutrophils increased after 1 Gy with a dose dependency noted after 10-25Gy and alveolar septa thickening followed 5-25 Gy. A lower occludin 1 expression was observed in animals irradiated with the doses of 5 20 Gy, indicating an effect on vascular permeability. Anti-inflammatory therapy partially inhibited the increase of neutrophils at all radiation doses and the depletion of type II pneumocytes after doses of 1, 10, and 15 Gy. Occludin 1 did not decrease in the lungs of rats treated with the anti-inflammatory drugs as it did in most rats treated only with saline. Our results suggest that pneumocytes depletion is a major factor responsible for radiation pneumonitis development and that these changes may be compensated for provided radiation doses are below the threshold. PMID:15625787

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

    SciTech Connect

    Gordon, J; Snyder, K; Zhong, H; Chetty, I

    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

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

    SciTech Connect

    Lopez Guerra, Jose Luis; Gomez, Daniel; Zhuang Yan; Levy, Lawrence B.; Eapen, George; Liu Hongmei; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing

    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. Initial Evaluation of Treatment-Related Pneumonitis in Advanced-Stage Non-Small-Cell Lung Cancer Patients Treated With Concurrent Chemotherapy and Intensity-Modulated Radiotherapy

    SciTech Connect

    Yom, Sue S.; Liao Zhongxing . E-mail: zliao@mdanderson.org; Liu, H. Helen; Tucker, Susan L.; Hu, C.-S.; Wei Xiong; Wang Xuanming; Wang Shulian; Mohan, Radhe; Cox, James D.; Komaki, Ritsuko

    2007-05-01

    Purpose: To investigate the rate of high-grade treatment-related pneumonitis (TRP) in patients with advanced non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). Methods and Materials: From August 2002 to August 2005, 151 NSCLC patients were treated with IMRT. We excluded patients who did not receive concurrent chemotherapy or who had early-stage cancers, a history of major lung surgery, prior chest RT, a dose <50 Gy, or IMRT combined with three-dimensional conformal RT (3D-CRT). Toxicities were graded by Common Terminology Criteria for Adverse Events version 3.0. Grade {>=}3 TRP for 68 eligible IMRT patients was compared with TRP among 222 similar patients treated with 3D-CRT. Results: The median follow-up durations for the IMRT and 3D-CRT patients were 8 months (range, 0-27 months) and 9 months (range, 0-56 months), respectively. The median IMRT and 3D-CRT doses were 63 Gy. The median gross tumor volume was 194 mL (range, 21-911 mL) for IMRT, compared with 142 mL (range, 1.5-1,186 mL) for 3D-CRT (p = 0.002). Despite the IMRT group's larger gross tumor volume, the rate of Grade {>=}3 TRP at 12 months was 8% (95% confidence interval 4%-19%), compared with 32% (95% confidence interval 26%-40%) for 3D-CRT (p = 0.002). Conclusions: In advanced NSCLC patients treated with chemoradiation, IMRT resulted in significantly lower levels of Grade {>=}3 TRP compared with 3D-CRT. Clinical, dosimetric, and patient selection factors that may have influenced rates of TRP require continuing investigation. A randomized trial comparing IMRT with 3D-CRT has been initiated.

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

    SciTech Connect

    Pang, Qingsong; Wei, Qingyi; Xu, Ting; Yuan, Xianglin; Lopez Guerra, Jose Luis; Levy, Lawrence B.; Liu, Zhensheng; Gomez, Daniel R.; Zhuang, Yan; Wang, Li-E.; Mohan, Radhe; Komaki, Ritsuko; Liao, Zhongxing

    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.

  20. A Single Nucleotide Polymorphism in the MTHFR Gene is Associated with Risk of Radiation Pneumonitis in Lung Cancer Patients Treated with Thoracic Radiation Therapy

    PubMed Central

    Mak, Raymond H.; Alexander, Brian M.; Asomaning, Kofi; Heist, Rebecca S.; Liu, Chen-yu; Su, Li; Zhai, Rihong; Ancukiewicz, Marek; Napolitano, Brian; Niemierko, Andrzej; Willers, Henning; Choi, Noah C.; Christiani, David C.

    2011-01-01

    Background To study the association between functional single nucleotide polymorphisms (SNPs) in candidate genes from oxidative stress pathways, and risk of radiation pneumonitis (RP) in patients treated with thoracic radiation therapy (RT) for locally advanced lung cancer (LC). Methods We reviewed 136 patients treated with RT for LC between 2001 and 2007, and had prior genotyping of functional SNPs in oxidative stress genes including superoxide dismutase 2 (SOD2; rs4880) and methylenetetrahydrofolate reductase (MTHFR; rs1801131, rs1801133). RP events were retrospectively scored using the Common Terminology Criteria for Adverse Events, version 4.0. Cox proportional hazard regression was performed to identify clinical variables and genotypes associated with risk of grade ≥2 and grade ≥3 RP on univariate and multivariate analysis. P-values were corrected for multiple hypothesis testing. Results With a median follow-up of 21.4 months, the incidence of ≥grade 2 RP was 29% and ≥grade 3 RP was 14%. On multivariate analysis, after adjusting for clinical factors such as concurrent chemotherapy, and consolidation docetaxel, and lung dosimetric parameters such as V20 and mean lung dose, MTHFR genotype (rs1801131; AA versus AC/CC) was significantly associated with risk of ≥grade 2 RP (Hazard ratio [HR]: 0.37; 95% confidence interval [CI]: 0.18-0.76; p=0.006, corrected p=0.018) and ≥grade 3 RP (HR: 0.21; 95% CI: 0.06-0.70; p=0.01; corrected p=0.03). SOD2 genotype was not associated with RP. Conclusions Our study showed an association between MTHFR genotype and risk of clinically significant RP. Further study of MTHFR-related pathways may provide insight into the mechanisms behind RP. PMID:22144047

  1. Detection of human cytomegalovirus antigenaemia: a rapid diagnostic technique for predicting cytomegalovirus infection/pneumonitis in lung and heart transplant recipients.

    PubMed Central

    Egan, J. J.; Barber, L.; Lomax, J.; Fox, A.; Yonan, N.; Rahman, A. N.; Campbell, C. S.; Deiraniya, A. K.; Carroll, K. B.; Craske, J.

    1995-01-01

    BACKGROUND--New rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromised patients at risk of developing CMV disease. The use of human CMV antigenaemia as a predictor of clinical CMV infection and disease in lung and heart transplant recipients was studied prospectively. METHODS--Twenty three heart and nine lung transplant recipients who survived 40 days were observed by standard CMV surveillance with serological testing, culture, and by sequential testing for CMV antigenaemia. CMV antigenaemia testing is a rapid and quantifiable technique in which a viral lower matrix protein is detected in cytospin preparations of peripheral blood polymorphonuclear leucocytes (PMNLs) by immunofluorescent staining. RESULTS--Eleven patients developed CMV infection and five developed CMV disease (four pneumonitis, one duodenitis). These clinical events occurred at a median of 65 days following transplantation. CMV antigenaemia occurred in 17 patients at a median of 35 days following transplantation. Detection of CMV antigenaemia had a sensitivity of 100%, a specificity of 93.7%, and a positive predictive value of 94.1% for CMV related illness. CMV antigenaemia was positive at a significant interval before the clinical event. High levels of CMV antigenaemia (> 50 CMV antigen positive cells/2 x 10(5) PMNLs) occurred in 11 patients and five of these developed disease. CMV antigenaemia of > 50 CMV antigen positive cells/2 x 10(5) PMNLs had a positive predictive value of 45.5% for disease but a negative predictive value of 100%. Patients with disease had higher levels of antigenaemia than those without disease. CONCLUSIONS--CMV antigenaemia is a rapid diagnostic technique which can identify patients likely to develop CMV disease, potentially allowing early treatment. Images PMID:7886659

  2. Acute Arterial Emergencies

    PubMed Central

    Dagnone, L. E.; Brown, P. M.

    1983-01-01

    The response of the primary care physician in the initial assessment and management of acute arterial injuries will often be the deciding factor in survival of life, limb or organ system. Most arterial emergencies occur as a result of trauma, disruption of vessel wall and/or occlusion of flow. The common clinical syndromes of acute arterial emergencies are injuries to and beyond the aorta, acute aortic dissection, ruptured aortic aneurysm, and thromboembolic occlusive arterial disease. The role of arteriography and the urgency of definitive surgical repair in acute arterial emergencies is summarized. PMID:21283323

  3. Acute phase reaction and acute phase proteins*

    PubMed Central

    Gruys, E.; Toussaint, M.J.M.; Niewold, T.A.; Koopmans, S.J.

    2005-01-01

    A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes, negative and positive acute phase proteins (APPs) with function and associated pathology is given. It appears that APPs represent appropriate analytes for assessment of animal health. Whereas they represent non-specific markers as biological effect reactants, they can be used for assessing nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. When such acute phase index is applied to separate healthy animals from animals with some disease, much better results are obtained than with single analytes and statistically acceptable results for culling individual animals may be reached. Unfortunately at present no cheap, comprehensive and easy to use system is available for assessing various acute phase proteins in serum or blood samples at the same time. Protein microarray or fluid phase microchip technology may satisfy this need; and permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease specific variables. Applying such technology may help to solve health problems in various countries not only in animal husbandry but also in human populations. PMID:16252337

  4. Zebrafish Models for Human Acute Organophosphorus Poisoning

    PubMed Central

    Faria, Melissa; Garcia-Reyero, Natàlia; Padrós, Francesc; Babin, Patrick J.; Sebastián, David; Cachot, Jérôme; Prats, Eva; Arick II, Mark; Rial, Eduardo; Knoll-Gellida, Anja; Mathieu, Guilaine; Le Bihanic, Florane; Escalon, B. Lynn; Zorzano, Antonio; Soares, Amadeu M.V.M; Raldúa, Demetrio

    2015-01-01

    Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning. PMID:26489395

  5. Zebrafish Models for Human Acute Organophosphorus Poisoning.

    PubMed

    Faria, Melissa; Garcia-Reyero, Natàlia; Padrós, Francesc; Babin, Patrick J; Sebastián, David; Cachot, Jérôme; Prats, Eva; Arick Ii, Mark; Rial, Eduardo; Knoll-Gellida, Anja; Mathieu, Guilaine; Le Bihanic, Florane; Escalon, B Lynn; Zorzano, Antonio; Soares, Amadeu M V M; Raldúa, Demetrio

    2015-01-01

    Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning. PMID:26489395

  6. Proton Resonance Frequency Chemical Shift Thermometry: Experimental Design and Validation Towards High-Resolution Non-Invasive Temperature Monitoring, and in vivo Experience in a Non-human Primate Model of Acute Ischemic Stroke

    PubMed Central

    Mao, Hui; Howell, Leonard; Zhang, Xiaodong; Pate, K S; Magrath, P R; Tong, Frank; Wei, L; Qiu, D; Fleischer, C; Oshinski, J N

    2016-01-01

    BACKGROUND AND PURPOSE Applications for non-invasive biological temperature monitoring are widespread in biomedicine, and of particular interest in the context of brain temperature regulation, where traditionally costly and invasive monitoring schemes limit their applicability in many settings. Brain thermal regulation therefore remains controversial, motivating the development of non-invasive approaches such as temperature-sensitive NMR phenomena. The purpose of this work was to compare the utility of competing approaches to MR thermometry (MRT) employing proton resonance frequency chemical shift. Three methodologies were tested, hypothesizing the feasibility of a fast and accurate approach to chemical shift thermometry, in a phantom study at 3.0 Tesla. MATERIALS AND METHODS A conventional, paired approach (DIFF-1), an accelerated single-scan approach (DIFF-2), and a new, further accelerated strategy (DIFF-3) were tested. Phantom temperatures were modulated during real-time fiber optic temperature monitoring, with MRT derived simultaneously from temperature-sensitive changes in the water proton chemical shift (~0.01 ppm/°C). MRT was subsequently performed in a series of in vivo non-human primate experiments under physiologic and ischemic conditions testing its reproducibility and overall performance. RESULTS Chemical shift thermometry demonstrated excellent agreement with phantom temperatures for all three approaches (DIFF-1 linear regression R2=0.994, p<0.001, acquisition time 4 min 40 s; DIFF-2 R2=0.996, p<0.001, acquisition time 4 min; DIFF-3 R2=0.998, p<0.001, acquisition time 40 s). CONCLUSION These findings confirm the comparability in performance of three competing approaches MRT, and present in vivo applications under physiologic and ischemic conditions in a primate stroke model. PMID:25655874

  7. Biomass - chemicals

    SciTech Connect

    Kovaly, K.A.

    1982-08-01

    A host of industrial chemicals, specialty items, solvents, plastics, elastomers, fibers and films can be produced from agricultural crops, wood, paper mill wastes, food processing wastes, municipal waste and sewage. Existing chemical processes based on readily renewable plant materials are reviewed. These include ethanol and acetone-butanol fermentations, oilseed chemicals, furfural and cellulosics. (Refs. 16).

  8. Chemical sensor

    NASA Technical Reports Server (NTRS)

    Rauh, R. David (Inventor)

    1990-01-01

    A sensor for detecting a chemical substance includes an insertion element having a structure which enables insertion of the chemical substance with a resulting change in the bulk electrical characteristics of the insertion element under conditions sufficient to permit effective insertion; the change in the bulk electrical characteristics of the insertion element is detected as an indication of the presence of the chemical substance.

  9. Acute kidney injury.

    PubMed

    Lang, Joanna; Zuber, Kim; Davis, Jane

    2016-04-01

    Acute kidney injury (AKI) complicates up to 20% of all hospital admissions. Responding to the increase in admissions, complications, mortality, morbidity, and cost of AKI, Kidney Disease: Improving Global Outcomes convened an expert panel to study the issue, review the literature, and publish guidelines to evaluate and treat patients with AKI in the acute setting. This article reviews those guidelines. PMID:27023656

  10. Acute Disseminated Encephalomyelitis.

    PubMed

    Gray, Matthew Philip; Gorelick, Marc H

    2016-06-01

    Acute disseminated encephalomyelitis is a primarily pediatric, immune-mediated disease characterized by demyelination and polyfocal neurologic symptoms that typically occur after a preceding viral infection or recent immunization. This article presents the pathophysiology, diagnostic criteria, and magnetic resonance imaging characteristics of acute disseminated encephalomyelitis. We also present evaluation and management strategies. PMID:27253358

  11. Poznan acute Astronomical Observatory

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    This Poznan acute Astronomical Observatory is a unit of the Adam Mickiewicz University, located in Poznan acute, Poland. From its foundation in 1919, it has specialized in astrometry and celestial mechanics (reference frames, dynamics of satellites and small solar system bodies). Recently, research activities have also included planetary and stellar astrophysics (asteroid photometry, catalysmic b...

  12. Chemical Leukoderma.

    PubMed

    Bonamonte, Domenico; Vestita, Michelangelo; Romita, Paolo; Filoni, Angela; Foti, Caterina; Angelini, Gianni

    2016-01-01

    Chemical leukoderma, often clinically mimicking idiopathic vitiligo and other congenital and acquired hypopigmentation, is an acquired form of cutaneous pigment loss caused by exposure to a variety of chemicals that act through selective melanocytotoxicity. Most of these chemicals are phenols and aromatic or aliphatic catechols derivatives. These chemicals, however, are harmful for melanocytes in individuals with an individual susceptibility. Nowadays, chemical leukoderma is fairly common, caused by common domestic products. The presence of numerous acquired confetti- or pea-sized macules is clinically characteristic of chemical leukoderma, albeit not diagnostic. Other relevant diagnostic elements are a history of repeated exposure to a known or suspected depigmenting agent at the sites of onset and a macules distribution corresponding to sites of chemical exposure. Spontaneous repigmentation has been reported when the causative agent is avoided; the repigmentation process is perifollicular and gradual, taking place for a variable period of weeks to months. PMID:27172302

  13. Experimental models of hepatotoxicity related to acute liver failure.

    PubMed

    Maes, Michaël; Vinken, Mathieu; Jaeschke, Hartmut

    2016-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. PMID:26631581

  14. Experimental models of hepatotoxicity related to acute liver failure

    PubMed Central

    Maes, Michaël; Vinken, Mathieu; Jaeschke, Hartmut

    2015-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. PMID:26631581

  15. FISH ACUTE TOXICITY SYNDROMES: APPLICATION TO THE DEVELOPMENT OF MECHANISM-SPECIFIC QSARS (QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIPS)

    EPA Science Inventory

    Predictive models based on quantitative structure activity relationships (QSARs), are used as rapid screening tools to identify potentially hazardous chemicals. Several QSARs are now available that predict the acute toxicity of narcotic-industrial chemicals. Predictions for compo...

  16. Comparative Toxicity of Eight Oil Dispersants, Louisiana Sweet Crude Oil (LSC) and Chemically Dispersed LSC to Two Aquatic Test Species

    EPA Science Inventory

    This study describes the acute toxicity of eight commercial oil dispersants, Louisiana sweet crude oil (LSC), and chemically dispersed LSC. The approach utilized consistent test methodologies within a single laboratory in assessing the relative acute toxicity of the eight dispers...

  17. Comparison of acute toxicity of process chemicals used in the oil refinery industry, tested with the diatom Chaetoceros gracilis, the flagellate Isochrysis galbana, and the zebra fish, Brachydanio rerio

    SciTech Connect

    Roseth, S.; Edvardsson, T.; Botten, T.M.; Fuglestad, J.; Fonnum, F.; Stenersen, J.

    1996-07-01

    Chemicals under the trade names Nalco 537-DA, Nalco 625, Nalco 7607, Nalco 5165, Ivamin, and technical monoethanolamine are used extensively in the oil refinery industry. Aquatic toxicity tests were conducted using zebra fish fry (Brachydanio rerio) and the unicellular algae Isochrysis galbana (a flagellate) and Chaetoceros gracilis (a diatom). Inhibition of cell division, chlorophyll content, and {sup 14}CO{sub 2} uptake in the algae were sensitive end points. The effective concentrations (EC50s) of growth inhibition were 0.1 mg/L (Ivamin; I. galbana), 0.8 mg/L (Nalco 7607; I. galbana), 6 mg/L (Nalco 625; I. galbana), 10 mg/L (Nalco 5165; C. gracilis), and 15 mg/L (Nalco 537-DA; C. gracilis). The lethal concentrations (LC50s) (96 h) toward zebra fish fry was 1 mg/L for Nalco 7607, 6.5 mg/L for Nalco 537-DA, 7.1 mg/L for Nalco 625, and 20 mg/L for Ivamin 803. Monoethanolamine had an LC50 higher than 5,000 mg/L. Nalco 5165 was not tested on fish fry. The heartbeat frequency of fish embryos was reduced by 2.5 mg/L Nalco 537-DA, but this was an insensitive end point for the other chemicals.

  18. Survival from acute renal failure after severe burns.

    PubMed

    Sawada, Y; Momma, S; Takamizawa, A; Nishida, S

    1984-12-01

    We describe a patient with 50 per cent, third degree flame burns who had a history of paint thinner inhalation for over 10 years. Moreover, chlorpromazine had been administered for the treatment of insomnia caused by chronic thinner intoxication. He developed oliguric acute renal failure soon after the burn injury, although adequate resuscitation therapy was given, and survived following frequent haemodialysis. Although survival from acute renal failure after severe burns is rare, once the diagnosis of acute renal failure has been made, haemodialysis should be instituted as early as possible. Furthermore, in a severely burnt patient with episodes of chronic and acute intoxication from organic chemicals or drugs which may have caused renal damage, acute renal failure may occur, so that careful observation is advised. PMID:6525538

  19. Single-nucleotide polymorphisms of TGFβ1 and ATM associated with radiation-induced pneumonitis: a prospective cohort study of thoracic cancer patients in China

    PubMed Central

    Xiao, Ying; Yuan, Xianglin; Qiu, Hong; Li, Qianxia

    2015-01-01

    Background: We examined the effects of the rs1800469 and rs1800470 single nucleotide polymorphisms (SNPs) of the transforming growth factor-β1 (TGFβ1) gene and the rs189037 and rs373759 SNPs of the ataxia telangiectasia mutated (ATM) gene on the risk of radiation-induced pneumonitis (RP) in patients who underwent radiotherapy for various thoracic malignancies. Methods: We determined the genotype and allele distributions of rs1800469 (C-509T), rs1800470 (C869T), rs189037 (A-111G), and rs373759 (126713 G>A) in 141 Han Chinese patients who underwent definitive thoracic radiotherapy (50 to 77 Gy, 5 days/wk) for lung cancer (small cell or non-small cell tumors, n = 97), esophageal squamous cell carcinoma (ESCC, n = 27), or mediastinal cancer (n = 17). Clinical variables were evaluated using multivariate logistic regression models to calculate the relative risk of RP associated with the clinical variables, and a Pearson correlation analysis was used to evaluate the relationship between the SNP genotypes and alleles and the incidence of RP for the various risk factors. Results: The T alleles of rs1800470 (CT/TT) and rs1800469 (CT/TT) and the G allele of rs189037 (GA/GG) were associated with the risk of ≥ grade-2 RP in the ESCC patients (P = 0.0006, P = 0.0127, and P = 0.0412, respectively), and that the A alleles of rs189037 (AG/AA) and rs373759 (AG/AA) were associated with the risk of ≥ grade-2 RP in the patients with mediastinal cancer (P = 0.0063 and P = 0.0003, respectively). None of the SNP genotypes were associated with the risk of RP in lung cancer patients. Conclusion: The T alleles of the rs1800470 (CT/TT) and rs1800469 (CT/TT) SNPs of TGFβ1 and the G allele of the rs189037 (GA/GG) SNP of ATM are independent risk factors for RP in Chinese ESCC patients, and the A alleles of the rs189037 (AG/AA) and rs373759 (AG/AA) SNPs of ATM are independent risk factors for RP in Chinese patients with mediastinal cancer. These SNPs might represent useful biomarkers for

  20. 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

    SciTech Connect

    Liu Fan; Yorke, Ellen D.; Belderbos, Jose S.A.; Borst, Gerben R.; Rosenzweig, Kenneth E.; Lebesque, Joos V.; Jackson, Andrew

    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.

  1. A Dose-Volume Analysis of Radiation Pneumonitis in Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy

    SciTech Connect

    Barriger, R. Bryan; Forquer, Jeffrey A.; Brabham, Jeffrey G.; Andolino, David L.; Shapiro, Ronald H.; Henderson, Mark A.; Johnstone, Peter A.S.; Fakiris, Achilles J.

    2012-01-01

    Purpose: To examine the rates and risk factors of radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). Methods and Materials: Dosimetry records for 251 patients with lymph node-negative Stage I-IIB NSCLC and no prior chest radiation therapy (RT) treated with SBRT were reviewed. Patients were coded on the basis of the presence of at least Grade (G) 2 RP using the Common Toxicity Criteria version 2 criteria. Radiation doses, V5, V10, V20, and mean lung dose (MLD) data points were extracted from the dose-volume histogram (DVH). Results: Median PTV volume was 48 cc. Median prescribed radiation dose was 60 Gy delivered in three fractions to the 80% isodose line. Median age at treatment was 74 years. Median follow-up was 17 months. RP was reported after treatment of 42 lesions: G1 in 19 (8%), G2 in 17 (7%), G3 in 5 (2%), and G4 in 1 (0.4%). Total lung DVHs were available for 143 patients. For evaluable patients, median MLD, V5, V10, and V20 were 4.1 Gy, 20%, 12%, and 4%, respectively. Median MLDs were 4 Gy and 5 Gy for G0-1 and G2-4 groups, respectively (p = 0.14); median V5 was 20% for G0-1 and 24% for G2-4 (p = 0.70); median V10 was 12% in G0-1 and 16% in G2-4 (p = 0.08), and median V20 was 4% in G0-1 and 6.6% in G2-4 (p = 0.05). G2-4 RP was noted in 4.3% of patients with MLD {<=}4 Gy compared with 17.6% of patients with MLD >4 Gy (p = 0.02), and in 4.3% of patients with V20 {<=}4% compared with 16.4% of patients with V20 >4% (p = 0.03). Conclusion: Overall rate of G2-4 RP in our population treated with SBRT was 9.4%. Development of symptomatic RP in this series correlated with MLD and V20.

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

    SciTech Connect

    Cunliffe, Alexandra; Armato, Samuel G.; Castillo, Richard; Pham, Ngoc; Guerrero, Thomas; Al-Hallaq, Hania A.

    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

  3. Differences in Virulence Between Bovine-Derived Clinical Isolates of Pasteurella multocida Serotype A from the UK and the USA in a Model of Bovine Pneumonic Pasteurellosis.

    PubMed

    Dagleish, M P; Bayne, C W; Moon, G G; Finlayson, J; Sales, J; Williams, J; Hodgson, J C

    2016-07-01

    ), caused pneumonic pasteurellosis in a single host with significantly different severity of pathology. This information is relevant to the development of novel vaccine control and interpretation of diagnostic results. PMID:27338785

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

    PubMed Central

    Cunliffe, Alexandra; Armato, Samuel G.; Castillo, Richard; Pham, Ngoc; Guerrero, Thomas; Al-Hallaq, Hania A.

    2015-01-01

    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

  5. Dose-Volume Analysis of Radiation Pneumonitis in Non-Small-Cell Lung Cancer Patients Treated With Concurrent Cisplatinum and Etoposide With or Without Consolidation Docetaxel

    SciTech Connect

    Barriger, R. Bryan; Fakiris, Achilles J.; Hanna, Nasser; Yu Menggang; Mantravadi, Prasad; McGarry, Ronald C.

    2010-12-01

    Purpose: To examine the rates and risk factors for radiation pneumonitis (RP) in non-small-cell lung cancer (NSCLC) patients treated with chemoradiotherapy. Methods and Materials: We reviewed dosimetry records from Stage III NSCLC patients treated on a prospective randomized trial. Patients received concurrent cisplatinum/etoposide with radiation therapy to 59.4Gy. A total of 243 patients were enrolled; 167 did not experience progression and were randomized to observation (OB) or consolidation docetaxel (CD). Toxicity was coded based on the presence of Grade 0 to 1 vs. Grade 2 to 5 RP using the Common Toxicity Criteria and Adverse Events (CTCAE) v3.0. Results: Median age and follow-up were 63 years and 16 months, respectively. Overall, Grade 0 to 1 and Grade 2 to 5 RP were reported in 226 patients and 17 patients (7%) respectively. Median mean lung dose (MLD), V5, V20, and V30 for evaluable patients were 18 Gy, 52%, 35%, and 29%. MLD in Grade 0 to 1 and Grade 2 to 5 patients was 1,748 c Gy and 2,013 cGy in respectively (p = 0.12). Grade 2 to 5 RP developed in 2.2% and 19% of patients with MLD < 18 Gy and MLD > 18 Gy, respectively (p = 0.015). Mean V20 was 33.7% and 37.7% for Grade 0 to 1 and Grade 2 to 5 groups, respectively (p = 0.29). Grade 2 to 5 RP developed in 4.8% and 17% of patients with V20 < 35% and V20 > 35%, respectively. The OB and CD groups had similar MLD and V20, and the RP rates were 3.6% and 14.6%, respectively (p = 0.015). Patients who developed Grade 0 to 1 and Grade 2 to 5 RP had similar mean V5, V10, V15, V20, V25, V30, age, smoking history, and tumor characteristics. Conclusions: The overall rate of Grade 2 to 5 RP was 7% in patients treated with chemoradiotherapy. In this analysis, predictive factors for RP were MLD > 18 Gy and treatment with CD.

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

    SciTech Connect

    Anthony, G; Cunliffe, A; Armato, S; Al-Hallaq, H; Castillo, R; Pham, N; Guerrero, T

    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

  7. [Chemical weapons and chemical terrorism].

    PubMed

    Nakamura, Katsumi

    2005-10-01

    Chemical Weapons are kind of Weapons of Mass Destruction (WMD). They were used large quantities in WWI. Historically, large quantities usage like WWI was not recorded, but small usage has appeared now and then. Chemical weapons are so called "Nuclear weapon for poor countrys" because it's very easy to produce/possession being possible. They are categorized (1) Nerve Agents, (2) Blister Agents, (3) Cyanide (blood) Agents, (4) Pulmonary Agents, (5) Incapacitating Agents (6) Tear Agents from the viewpoint of human body interaction. In 1997 the Chemical Weapons Convention has taken effect. It prohibits chemical weapons development/production, and Organization for the Prohibition of Chemical Weapons (OPCW) verification regime contributes to the chemical weapons disposal. But possibility of possession/use of weapons of mass destruction by terrorist group represented in one by Matsumoto and Tokyo Subway Sarin Attack, So new chemical terrorism countermeasures are necessary. PMID:16296384

  8. Acute Hepatic Porphyria

    PubMed Central

    Bissell, D. Montgomery; Wang, Bruce

    2015-01-01

    The porphyrias comprise a set of diseases, each representing an individual defect in one of the eight enzymes mediating the pathway of heme synthesis. The diseases are genetically distinct but have in common the overproduction of heme precursors. In the case of the acute (neurologic) porphyrias, the cause of symptoms appears to be overproduction of a neurotoxic precursor. For the cutaneous porphyrias, it is photosensitizing porphyrins. Some types have both acute and cutaneous manifestations. The clinical presentation of acute porphyria consists of abdominal pain, nausea, and occasionally seizures. Only a small minority of those who carry a mutation for acute porphyria have pain attacks. The triggers for an acute attack encompass certain medications and severely decreased caloric intake. The propensity of females to acute attacks has been linked to internal changes in ovarian physiology. Symptoms are accompanied by large increases in delta-aminolevulinic acid and porphobilinogen in plasma and urine. Treatment of an acute attack centers initially on pain relief and elimination of inducing factors such as medications; glucose is administered to reverse the fasting state. The only specific treatment is administration of intravenous hemin. An important goal of treatment is preventing progression of the symptoms to a neurological crisis. Patients who progress despite hemin administration have undergone liver transplantation with complete resolution of symptoms. A current issue is the unavailability of a rapid test for urine porphobilinogen in the urgent-care setting. PMID:26357631

  9. Chemical microsensors

    DOEpatents

    Li, DeQuan; Swanson, Basil I.

    1995-01-01

    An article of manufacture is provided including a substrate having an oxide surface layer and a selective thin film of a cyclodextrin derivative chemically bound upon said substrate, said film is adapted for the inclusion of a selected organic compound therewith. Such an article can be either a chemical sensor capable of detecting a resultant mass change from inclusion of the selected organic compound or a chemical separator capable of reversibly selectively separating a selected organic compound.

  10. Acute Lung Failure

    PubMed Central

    Mac Sweeney, Rob; McAuley, Daniel F.; Matthay, Michael A.

    2013-01-01

    Lung failure is the most common organ failure seen in the intensive care unit. The pathogenesis of acute respiratory failure (ARF) can be classified as (1) neuromuscular in origin, (2) secondary to acute and chronic obstructive airway diseases, (3) alveolar processes such as cardiogenic and noncardiogenic pulmonary edema and pneumonia, and (4) vascular diseases such as acute or chronic pulmonary embolism. This article reviews the more common causes of ARF from each group, including the pathological mechanisms and the principles of critical care management, focusing on the supportive, specific, and adjunctive therapies for each condition. PMID:21989697

  11. Acute porphyric disorders.

    PubMed

    Moore, A W; Coke, J M

    2000-09-01

    Acute porphyrias are classified into 3 distinct groups of rare genetic disorders of metabolic enzyme biosynthesis. Acute porphyrias can significantly impact multiple organ systems, which often provides a challenge to the dentist presented with such a patient. A case of hereditary coproporphyria is reported in a patient with many of the classical signs and symptoms. The patient also had complex dental needs that required special medical and pharmacotherapeutic modifications. The acute porphyrias are reviewed by the authors with presentation of this challenging case. Recommendations for other dental health care professionals encountering these patients are then presented. PMID:10982942

  12. SURVEY OF CHEMICAL AND BIOLOGICAL STRUCTURE IN THREE FLORIDA BAYOU-ESTUARIES.

    EPA Science Inventory

    Structural and functional characteristics of the benthic biota were determined and compared for three urbanized bayous, in conjuction with sediment chemical quality and acute toxicity. Sediment chemical contamination in the bayous was common. Numerical sediment quality assessmen...

  13. A SURVEY OF CHEMICAL AND BIOLOGICAL STRUCTURE IN THREE FLORIDA BAYOU-ESTUARIES

    EPA Science Inventory

    Structural and functional characteristics of the benthic biota were determined and compared for three urbanized bayous, in conjuction with sediment chemical quality and acute toxicity. Sediment chemical contamination in the bayous was common. Numerical sediment quality assessmen...

  14. Health effects of chemical products.

    PubMed

    Steensberg, J

    1982-01-01

    An outline is given of the data on human health effects that are needed as a foundation for the administration of legislation on chemical substances and products. Danish data on mortality and morbidity from acute poisoning and some published clinical studies are presented. Serious problems may persist in subgroups of the population and the prevention of acute poisoning is still a basic aim of this legislation. Allergic reactions to chemicals are discussed. Not all sensitized individuals can be protected but steps should be taken to prevent contact with the sensitizing agents that are of the greatest public health importance. Chronic health effects following exposure to chemicals have influenced the recent strengthening of regulations but carcinogenic risks especially are extremely difficult for administrative and political systems to handle in an approximately rational way. While we are reducing the use of suspected carcinogenic chemicals our populations must, however, be given a greater appreciation of the cancer risk problem, particularly the fact that we cannot eliminate all cancer risks. Biological monitoring of human populations is a necessary supplement to the traditional registration of diseases as part of our health surveillance systems. Fortunately our societies have been able to pay increasing attention to the long-term public health consequences of exposures to chemical factors in our environment. PMID:6236969

  15. Translational toxicological research: investigating and preventing acute lung injury in organophosphorus insecticide poisoning.

    PubMed

    Hulse, Elspeth J; Clutton, R E; Drummond, G; Eddleston, M

    2014-06-01

    Poisoning through ingestion of organophosphorus (OP) insecticide is a leading cause of suicide globally. Severe poisoning with OP compounds creates an unconscious, paralysed patient with respiratory failure. These symptoms make pulmonary aspiration of stomach contents highly likely, potentially causing an acute lung injury. To explore this hypothesis, we created a Gottingen minipig pulmonary aspiration model (n=26) to investigate the mechanism and severity of lung injury created through pulmonary instillation of 0.5 mL/kg mixtures of porcine gastric juice (GJ), OP and/or its solvent. Early results show that aspiration of OP and GJ causes pulmonary neutrophil sequestration, alveolar haemorrhage and interstitial oedema, with disruption of the alveolar-capillary membrane. Further measurements will include quantitative CT imaging, histopathology scoring, acute lung injury biomarkers and respiratory function. In order to test the validity of the minipig model, a pilot study in Sri Lanka has been devised to observe signs of lung injury in human patients who have ingested OP insecticide with or without clinical evidence of pulmonary aspiration. Lung injury will be assessed with PaO2/FIO2 ratios and physiological dead space measurement. Blood, bronchoalveolar lavage and urine will be taken at 24 and 48 h after poisoning and at 3-4 h in surgical control patients to measure acute lung injury biomarkers. An unpublished toxicology study from Sri Lanka, 2011-2012, showed that over 40% of unconscious poisoned patients with a GCS <9 were not intubated for ambulance transfer between rural and district hospitals. Delay in intubation leads to aspiration pneumonitis and pneumonia in 38%-45% of unconscious poisoned patients. We hypothesise that non-drug assisted placement of supraglottic airways may be a good tool for use in unconscious poisoned patients requiring transfer from small rural hospitals in Asia. They could confer better airway protection than no airway intervention

  16. Weight Loss & Acute Porphyria

    MedlinePlus

    ... Sale You are here Home Diet and Nutrition Weight loss & acute Porphyria Being overweight is a particular problem ... one of these diseases before they enter a weight-loss program. Also, they should not participate in a ...

  17. Acute mountain sickness

    MedlinePlus

    High altitude cerebral edema; Altitude anoxia; Altitude sickness; Mountain sickness; High altitude pulmonary edema ... Acute mountain sickness is caused by reduced air pressure and lower oxygen levels at high altitudes. The faster you ...

  18. Acute respiratory distress syndrome

    MedlinePlus

    ... chap 33. Lee WL, Slutsky AS. Acute hypoxemic respiratory failure and ARDS. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray and Nadel's Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: ...

  19. Acute coronary syndrome

    MedlinePlus

    Heart attack-ACS; Myocardial infarction-ACS; MI-ACS; Acute MI-ACS; ST-elevation myocardial infarction-ACS; Non-ST-elevation myocardial infarction-ACS; Unstable angina-ACS; Accelerating angina-ACS; New- ...

  20. Ear infection - acute

    MedlinePlus

    ... Risk factors for acute ear infections include: Attending day care (especially centers with more than 6 children) Changes ... hands and toys often. If possible, choose a day care that has 6 or fewer children. This can ...

  1. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... sudden inflammation of the pancreas manifested clinically by abdominal pain, nausea and dehydration that is usually self-limiting ... room for evaluation should they develop any abnormal abdominal pain symptoms. Conclusions While a rare event, acute pancreatitis ...

  2. Acute Flaccid Myelitis

    MedlinePlus

    ... on Facebook Tweet Share Compartir Acute flaccid myelitis (AFM) is a condition that affects the nervous system, ... from a variety of causes including viral infections. AFM is characterized by a sudden weakness in one ...

  3. Acute genital ulcers

    PubMed Central

    Delgado-García, Silvia; Palacios-Marqués, Ana; Martínez-Escoriza, Juan Carlos; Martín-Bayón, Tina-Aurora

    2014-01-01

    Acute genital ulcers, also known as acute vulvar ulcers, ulcus vulvae acutum or Lipschütz ulcers, refer to an ulceration of the vulva or lower vagina of non-venereal origin that usually presents in young women, predominantly virgins. Although its incidence is unknown, it seems a rare entity, with few cases reported in the literature. Their aetiology and pathogenesis are still unknown. The disease is characterised by an acute onset of flu-like symptoms with single or multiple painful ulcers on the vulva. Diagnosis is mainly clinical, after exclusion of other causes of vulvar ulcers. The treatment is mainly symptomatic, with spontaneous resolution in 2 weeks and without recurrences in most cases. We present a case report of a 13-year-old girl with two episodes of acute ulcers that fit the clinical criteria for Lipschütz ulcers. PMID:24473429

  4. Acute Radiation Syndrome

    MedlinePlus

    ... Dictionary Radiation Emergencies & Your Health Possible Health Effects Contamination and Exposure Acute Radiation Syndrome (ARS) Cutaneous Radiation ... Decision Making in Radiation Emergencies Protective Actions Internal Contamination Clinical Reference (ICCR) Application Psychological First Aid in ...

  5. Feigning Acute Intermittent Porphyria

    PubMed Central

    Elkhatib, Rania; Idowu, Modupe; Brown, Gregory S.; Jaber, Yasmeen M.; Reid, Matthew B.; Person, Cheryl

    2014-01-01

    Acute intermittent porphyria (AIP) is an autosomal dominant genetic defect in heme synthesis. Patients with this illness can have episodic life-threatening attacks characterized by abdominal pain, neurological deficits, and psychiatric symptoms. Feigning this illness has not been reported in the English language literature to date. Here, we report on a patient who presented to the hospital with an acute attack of porphyria requesting opiates. Diligent assessment of extensive prior treatment records revealed thirteen negative tests for AIP. PMID:25525547

  6. Chemical preconcentrator

    DOEpatents

    Manginell, Ronald P.; Frye-Mason, Gregory C.

    2001-01-01

    A chemical preconcentrator is disclosed with applications to chemical sensing and analysis. The preconcentrator can be formed by depositing a resistive heating element (e.g. platinum) over a membrane (e.g. silicon nitride) suspended above a substrate. A coating of a sorptive material (e.g. a microporous hydrophobic sol-gel coating or a polymer coating) is formed on the suspended membrane proximate to the heating element to selective sorb one or more chemical species of interest over a time period, thereby concentrating the chemical species in the sorptive material. Upon heating the sorptive material with the resistive heating element, the sorbed chemical species are released for detection and analysis in a relatively high concentration and over a relatively short time period. The sorptive material can be made to selectively sorb particular chemical species of interest while not substantially sorbing other chemical species not of interest. The present invention has applications for use in forming high-sensitivity, rapid-response miniaturized chemical analysis systems (e.g. a "chem lab on a chip").

  7. Chemical sensors

    DOEpatents

    Lowell, Jr., James R.; Edlund, David J.; Friesen, Dwayne T.; Rayfield, George W.

    1991-01-01

    Sensors responsive to small changes in the concentration of chemical species are disclosed, comprising (a) a mechanochemically responsive polymeric film capable of expansion or contraction in response to a change in its chemical environment, operatively coupled to (b) a transducer capable of directly converting said expansion or contraction to a measurable electrical response.

  8. Chemical sensors

    DOEpatents

    Lowell, J.R. Jr.; Edlund, D.J.; Friesen, D.T.; Rayfield, G.W.

    1991-07-02

    Sensors responsive to small changes in the concentration of chemical species are disclosed. The sensors comprise a mechanochemically responsive polymeric film capable of expansion or contraction in response to a change in its chemical environment. They are operatively coupled to a transducer capable of directly converting the expansion or contraction to a measurable electrical response. 9 figures.

  9. Chemical Peels

    MedlinePlus

    ... the complications or potential side effects of a chemical peel? Temporary or permanent change in skin color, particularly for women on birth control pills, who subsequently become pregnant or have a history of brownish facial ... after having a chemical peel? All peels require some follow-up care: ...

  10. Chemical Emergencies

    MedlinePlus

    ... agents such as sarin and VX. Many hazardous chemicals are used in industry - for example, chlorine, ammonia, and benzene. Some can be made from everyday items such as household cleaners. Although there are no guarantees of safety during a chemical emergency, you can take actions to protect yourself. ...

  11. Acute respiratory failure in pregnancy.

    PubMed

    Lapinsky, Stephen E

    2015-09-01

    Respiratory failure affects up to 0.2% of pregnancies, more commonly in the postpartum period. Altered maternal respiratory physiology affects the assessment and management of these patients. Respiratory failure may result from pregnancy-specific conditions such as preeclampsia, amniotic fluid embolism or peripartum cardiomyopathy. Pregnancy may increase the risk or severity of other conditions, including thromboembolism, asthma, viral pneumonitis, and gastric acid aspiration. Management during pregnancy is similar to the nonpregnant patient. Endotracheal intubation in pregnancy carries an increased risk, due to airway edema and rapid oxygen desaturation following apnea. Few data are available to direct prolonged mechanical ventilation in pregnancy. Chest wall compliance is reduced, perhaps permitting slightly higher airway pressures. Optimizing oxygenation is important, but data on the use of permissive hypercapnia are limited. Delivery of the fetus does not always improve maternal respiratory function, but should be considered if benefit to the fetus is anticipated. PMID:27512467

  12. Development of acute lung injury after the combination of intravenous bleomycin and exposure to hyperoxia in rats.

    PubMed Central

    Hay, J G; Haslam, P L; Dewar, A; Addis, B; Turner-Warwick, M; Laurent, G J

    1987-01-01

    Pulmonary toxicity is an important adverse effect of bleomycin treatment. Very little is known of the mechanisms underlying the development of lung injury, especially after intravenous administration, or how it can be modulated. In this study acute lung injury induced by bleomycin has been examined in rats by assessment of alveolar lavage cell profiles, histological examination, and measurement of the total pulmonary extravascular albumin space. Intratracheal instillation of bleomycin 1.5 mg resulted in a severe pneumonitis with influx of inflammatory cells into the alveoli as assessed by alveolar lavage, oedema of the alveolar walls, and up to an eight fold increase in the total pulmonary extravascular albumin space, maximal at 72 hours. Intravenous bleomycin 0.15-5 mg produced no detectable injury when assessed in these ways. Exposure to hyperoxia (40-90%) after intravenous bleomycin, however, induced lung injury similar to that produced by intratracheal bleomycin. A much more severe injury followed administration of intravenous bleomycin after an exposure to hyperoxia, which itself resulted in lung injury; but lung injury was still detectable after bleomycin when the exposure to hyperoxia was insufficient to induce changes in control animals. Lung injury was not observed when the exposure to hyperoxia preceded bleomycin treatment. These results indicate the importance of oxygen in the pathways leading to acute lung injury following intravenous bleomycin. We conclude that exposure to oxygen might induce lung injury during and after bleomycin treatment, and suggest that in these circumstances oxygen therapy should be kept to a minimum. PMID:2443992

  13. Differentiating Acute Otitis Media and Acute Mastoiditis in Hospitalized Children.

    PubMed

    Laulajainen-Hongisto, Anu; Aarnisalo, Antti A; Jero, Jussi

    2016-10-01

    Acute otitis media is a common infection in children. Most acute otitis media episodes can be treated at an outpatient setting with antimicrobials, or only expectant observation. Hospital treatment with parenteral medication, and myringotomy or tympanostomy, may be needed to treat those with severe, prolonged symptoms, or with complications. The most common intratemporal complication of acute otitis media is acute mastoiditis. If a child with acute mastoiditis does not respond to this treatment, or if complications develop, further examinations and other surgical procedures, including mastoidectomy, are considered. Since the treatment of complicated acute otitis media and complicated acute mastoiditis differs, it is important to differentiate these two conditions. This article focuses on the differential diagnostics of acute otitis media and acute mastoiditis in children. PMID:27613655

  14. [Pulmonary complications of acute myocardial infarct. Therapeutic orientation].

    PubMed

    Cano, A E; Meaney, E

    1975-01-01

    The heart and the lung make up an inseparable anatomic and functional unit. The changes in one affect the other and vice versa. In acute myocardial infarction a heart failure syndrome develops. This syndrome is characterized by passive pulmonary congestion, which leads to hypoxemia. This hypoxemia indicate the functional disturbance of the lung, and the hemodinamic evolution of the disease. Arterial gases determination is the best way to assess the sickness progression. A certain paralelism exists among the central venous saturation, cardiac insufficiency and the degree of pulmonary disfunction. Such a procedure is not very appreciable and does not substitute the direct analysis of the arterial PO2. The pulmonary complications in the myocardial infarction shock are directly responsable of death in 50% of the patients. To heart failure and shock, hipperfusion and hypoxia are added. Many vessels close due to the decrease in the pulmonary flow. This brings about the release of substances that are toxic to the vessel causing an inflammatory vascular reaction. The decrease in the flow harms the lung cell and for this reason atelectasia or alveolar colapse occur; besides inducing the formation of shunts. Under these conditions the lung compliance decreases. The areas that are badly ventilated and hypoperfused can easily become infected and pneumonitis and abscesses cause even more harm to the tissue. The decrease in the speed of circulation and hematologic changes of shock, induce a diseminated intravascular coagulation. What was stated before leads to an important reduction of the lung as a depurating organ and makes the shock irreversible. As far as therapy is concerned in the prevention of vascular colaps and the improvement of the oxemia, oxygen is very useful when there is a venous congestion (clinically, X rays, and oxemia). When the concentration of O2 is lower than 50% in the cases with slight cardiac failure; do not use oxygen in higher concentrations unless the

  15. Resolving some practical questions about Daphnia acute toxicity tests

    SciTech Connect

    Barera, Y.; Adams, W.J.

    1981-10-01

    Acute toxicity tests were performed with six age groups of Daphnia magna, ranging from less than or equal to6 h to 216 h, and with five chemicals, selected on the basis of their physical and chemical properties as well as their acute toxicity to D. magna. The age of the daphnids did not significantly alter the 48-h EC/sub 50/ values for the chemicals tested. The maximum difference observed in the 48-h EC/sub 50/ values between the 6-h and 216-h age groups was a factor of 3.9 for linear alkylbenzene sulfonate (LAS). For purposes of standardization, it appears that D. magna up to 48 h of age at the beginning of the test can be used to conduct acute toxicity tests with most chemicals. The results of static acute toxicity tests conducted with butylbenzyl phthalate (BBP) and D. magna in the presence and absence of several commonly used solvents indicate that the acute toxicity of this chemical is not altered by the use of a solvent carrier. The 48-h EC/sub 50/ value for BBP without a solvent was 1.0 mg/L, compared with a range of 1.6 to 2.2 mg/L when acetone, dimethylformamide, ethanol, or triethylene glycol were used as solvent carriers. The acute toxicities of the solvents in the absence of BBP were also determined for D. magna. The values ranged from 9.3 to 52.4 g/L. The results of static acute tests performed with D. magna and BBP in the presence of various concentrations of daphnid foods (algae or trout chow), indicate that the 48-h EC/sub 50/ values increase proportionally with an increase in food concentrations. These results suggest that acute toxicity tests with D. magna should be conducted in the presence of food with chemicals with a high Ksigma if the results are to be used to select the test concentrations for a chronic study with daphnids. The type of food and the concentration used in the acute test should be the same as those used in a chronic test.

  16. How Is Hypersensitivity Pneumonitis Treated?

    MedlinePlus

    ... treat severe chronic disease in some patients. Avoidance strategies If your doctor is able to identify the ... will recommend that you adopt the following avoidance strategies. Remove the causative substance if possible Replace workplace ...

  17. AN EPIDEMIC OF PNEUMONIC PLAGUE

    PubMed Central

    Kellogg, W. H.

    1920-01-01

    Dr. Kellogg calls on health authorities to wake from their apathy with reference to plague in California, and instead of restrictive measures to adopt an aggressive warfare. He points out that there is real danger to the country and urges adequate appropriations to exterminate the animal disease carriers while this may be done with certainty. PMID:18010342

  18. Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague

    PubMed Central

    Tiner, Bethany L.; Ponnusamy, Duraisamy; Baze, Wallace B.; Fitts, Eric C.; Popov, Vsevolod L.; van Lier, Christina J.; Erova, Tatiana E.

    2015-01-01

    Earlier, we showed that the Δlpp ΔmsbB Δail triple mutant of Yersinia pestis CO92 with deleted genes encoding Braun lipoprotein (Lpp), an acyltransferase (MsbB), and the attachment invasion locus (Ail), respectively, was avirulent in a mouse model of pneumonic plague. In this study, we further evaluated the immunogenic potential of the Δlpp ΔmsbB Δail triple mutant and its derivative by different routes of vaccination. Mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) route with two doses (2 × 106 CFU/dose) of the above-mentioned triple mutant with 100% survivability of the animals. Upon subsequent pneumonic challenge with 70 to 92 50% lethal doses (LD50) of wild-type (WT) strain CO92, all of the mice survived when immunization occurred by the i.m. route. Since Ail has virulence and immunogenic potential, a mutated version of Ail devoid of its virulence properties was created, and the genetically modified ail replaced the native ail gene on the chromosome of the Δlpp ΔmsbB double mutant, creating a Δlpp ΔmsbB::ailL2 vaccine strain. This newly generated mutant was attenuated similarly to the Δlpp ΔmsbB Δail triple mutant when administered by the i.m. route and provided 100% protection to animals against subsequent pneumonic challenge. Not only were the two above-mentioned mutants cleared rapidly from the initial i.m. site of injection in animals with no histopathological lesions, the immunized mice did not exhibit any disease symptoms during immunization or after subsequent exposure to WT CO92. These two mutants triggered balanced Th1- and Th2-based antibody responses and cell-mediated immunity. A substantial increase in interleukin-17 (IL-17) from the T cells of vaccinated mice, a cytokine of the Th17 cells, further augmented their vaccine potential. Thus, the Δlpp ΔmsbB Δail and Δlpp ΔmsbB::ailL2 mutants represent excellent vaccine candidates for plague, with the latter mutant still retaining Ail immunogenicity but with

  19. Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague.

    PubMed

    Tiner, Bethany L; Sha, Jian; Ponnusamy, Duraisamy; Baze, Wallace B; Fitts, Eric C; Popov, Vsevolod L; van Lier, Christina J; Erova, Tatiana E; Chopra, Ashok K

    2015-12-01

    Earlier, we showed that the Δlpp ΔmsbB Δail triple mutant of Yersinia pestis CO92 with deleted genes encoding Braun lipoprotein (Lpp), an acyltransferase (MsbB), and the attachment invasion locus (Ail), respectively, was avirulent in a mouse model of pneumonic plague. In this study, we further evaluated the immunogenic potential of the Δlpp ΔmsbB Δail triple mutant and its derivative by different routes of vaccination. Mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) route with two doses (2 × 10(6) CFU/dose) of the above-mentioned triple mutant with 100% survivability of the animals. Upon subsequent pneumonic challenge with 70 to 92 50% lethal doses (LD(50)) of wild-type (WT) strain CO92, all of the mice survived when immunization occurred by the i.m. route. Since Ail has virulence and immunogenic potential, a mutated version of Ail devoid of its virulence properties was created, and the genetically modified ail replaced the native ail gene on the chromosome of the Δlpp ΔmsbB double mutant, creating a Δlpp ΔmsbB::ailL2 vaccine strain. This newly generated mutant was attenuated similarly to the Δlpp ΔmsbB Δail triple mutant when administered by the i.m. route and provided 100% protection to animals against subsequent pneumonic challenge. Not only were the two above-mentioned mutants cleared rapidly from the initial i.m. site of injection in animals with no histopathological lesions, the immunized mice did not exhibit any disease symptoms during immunization or after subsequent exposure to WT CO92. These two mutants triggered balanced Th1- and Th2-based antibody responses and cell-mediated immunity. A substantial increase in interleukin-17 (IL-17) from the T cells of vaccinated mice, a cytokine of the Th17 cells, further augmented their vaccine potential. Thus, the Δlpp ΔmsbB Δail and Δlpp ΔmsbB::ailL2 mutants represent excellent vaccine candidates for plague, with the latter mutant still retaining Ail immunogenicity but

  20. 75 FR 14153 - National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances; Notice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-24

    ...A meeting of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances (NAC/AEGL Committee) will be held on April 13-15, 2010, in San Francisco, CA. At this meeting, the NAC/AEGL Committee will address, as time permits, the various aspects of the acute toxicity and the development of Acute Exposure Guideline Levels (AEGLs) for the following chemicals: 1,3-......

  1. Acute Respiratory Failure Caused by Hepatopulmonary Fistula in a Patient with Hepatocellular Carcinoma

    PubMed Central

    Lee, Jungsil; Kim, Yoon Jun; Kim, Hyung-Jun; Kim, Jee-Min; Kim, Young-Chan

    2016-01-01

    A 59-year-old man presented with acute dyspnea following sudden productive cough and expectoration of a full cup of "blood-tinged" sputum. He had been diagnosed with hepatitis B virus–related hepatocellular carcinoma and had received transarterial chemoembolization 5 years ago for a 20-cm hepatic mass; he denied any history of hematemesis and the last esophagogastroduodenoscopy from a year ago showed absence of varix. Chest computed tomography (CT) with angiography showed new appearance of right basal lung consolidation but no bleeding focus. Despite the use of systemic antibiotics, the patient developed respiratory failure on day 7 of hospitalization. After intubation, a massive amount of brown sputum with anchovy-paste-like consistency was suctioned via the endotracheal tube. Bronchoscopic toileting was performed and the patient was extubated. In the ward, he continued to expectorate the brown sputum. On day 25 of hospitalization, a repeat CT scan showed simultaneous disappearance of the pneumonic consolidation and the necrotic fluid within the hepatic mass, suggesting the presence of a fistula. He has continued to receive systemic antibiotics, sorafenib, and entecavir, and follow up by respiratory and hepato-oncology specialists. PMID:27433178

  2. Acute Respiratory Failure Caused by Hepatopulmonary Fistula in a Patient with Hepatocellular Carcinoma.

    PubMed

    Lee, Jungsil; Kim, Yoon Jun; Kim, Hyung-Jun; Kim, Jee-Min; Kim, Young-Chan; Choi, Sun Mi

    2016-07-01

    A 59-year-old man presented with acute dyspnea following sudden productive cough and expectoration of a full cup of "blood-tinged" sputum. He had been diagnosed with hepatitis B virus-related hepatocellular carcinoma and had received transarterial chemoembolization 5 years ago for a 20-cm hepatic mass; he denied any history of hematemesis and the last esophagogastroduodenoscopy from a year ago showed absence of varix. Chest computed tomography (CT) with angiography showed new appearance of right basal lung consolidation but no bleeding focus. Despite the use of systemic antibiotics, the patient developed respiratory failure on day 7 of hospitalization. After intubation, a massive amount of brown sputum with anchovy-paste-like consistency was suctioned via the endotracheal tube. Bronchoscopic toileting was performed and the patient was extubated. In the ward, he continued to expectorate the brown sputum. On day 25 of hospitalization, a repeat CT scan showed simultaneous disappearance of the pneumonic consolidation and the necrotic fluid within the hepatic mass, suggesting the presence of a fistula. He has continued to receive systemic antibiotics, sorafenib, and entecavir, and follow up by respiratory and hepato-oncology specialists. PMID:27433178

  3. Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

    PubMed

    Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

    2014-08-01

    Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. PMID:24929227

  4. Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Acute Leukemia

    ClinicalTrials.gov

    2013-10-07

    Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. Unnecessary Chemicals

    ERIC Educational Resources Information Center

    Johnson, Anita

    1978-01-01

    Discusses the health hazards resulting from chemical additions of many common products such as cough syrups, food dyes, and cosmetics. Steps being taken to protect consumers from these health hazards are included. (MDR)

  6. Chemical geodynamics

    NASA Astrophysics Data System (ADS)

    Zindler, A.; Hart, S.

    Consideration is given to the following three principal boundary conditions relating to the nature and development of chemical structure in the earth's mantle: (1) inferred scale lengths for mantle chemical heterogeneities, (2) interrelationships of the various isotopic tracers, and (3) the bulk composition of the earth. These boundary conditions are integrated with geophysical constraints in order to evaluate models for the development of the physical and chemical structure of the mantle. Data indicate that: (1) km-size heterogeneities can survive diffusive equilibrium for billions of years; (2) the mantle is chemically heterogeneous on both very small and very large scales; (3) isotopic heterogeneities in the mantle require the existence of four 'end-member' components (DMM, HIMU, EM I, and EM II) and are consistent with the existence of at least two additional components (BSE, PREMA); and (4) primitive undepleted mantle can made up no more than about 55 percent of the total mantle.

  7. Chemical sensors

    DOEpatents

    Lowell, Jr., James R.; Edlund, David J.; Friesen, Dwayne T.; Rayfield, George W.

    1992-01-01

    Sensors responsive to small changes in the concentration of chemical species are disclosed, comprising a mechanicochemically responsive polymeric film capable of expansion or contraction in response to a change in its chemical environment, either operatively coupled to a transducer capable of directly converting the expansion or contraction to a measurable electrical or optical response, or adhered to a second inert polymeric strip, or doped with a conductive material.

  8. Chemical sensors

    DOEpatents

    Lowell, J.R. Jr.; Edlund, D.J.; Friesen, D.T.; Rayfield, G.W.

    1992-06-09

    Sensors responsive to small changes in the concentration of chemical species are disclosed, comprising a mechanicochemically responsive polymeric film capable of expansion or contraction in response to a change in its chemical environment, either operatively coupled to a transducer capable of directly converting the expansion or contraction to a measurable electrical or optical response, or adhered to a second inert polymeric strip, or doped with a conductive material. 12 figs.

  9. Acute bronchial asthma.

    PubMed

    Grover, Sudhanshu; Jindal, Atul; Bansal, Arun; Singhi, Sunit C

    2011-11-01

    Acute asthma is the third commonest cause of pediatric emergency visits at PGIMER. Typically, it presents with acute onset respiratory distress and wheeze in a patient with past or family history of similar episodes. The severity of the acute episode of asthma is judged clinically and categorized as mild, moderate and severe. The initial therapy consists of oxygen, inhaled beta-2 agonists (salbutamol or terbutaline), inhaled budesonide (three doses over 1 h, at 20 min interval) in all and ipratropium bromide and systemic steroids (hydrocortisone or methylprednisolone) in acute severe asthma. Other causes of acute onset wheeze and breathing difficulty such as pneumonia, foreign body, cardiac failure etc. should be ruled out with help of chest radiography and appropriate laboratory investigations in first time wheezers and those not responding to 1 h of inhaled therapy. In case of inadequate response or worsening, intravenous infusion of magnesium sulphate, terbutaline or aminophylline may be used. Magnesium sulphate is the safest and most effective alternative among these. Severe cases may need ICU care and rarely, ventilatory support. PMID:21769523

  10. DETERMINANTS OF VARIABILITY IN ACUTE TO CHRONIC TOXICITY RATIOS IN AQUATIC INVERTEBRATES AND FISH

    EPA Science Inventory

    Variability in acute to chronic ratios (ACRs; LC50/chronic value) has been a continuing interest in aquatic toxicology because of the reliance on ACRs to estimate chronic toxicity for chemicals and species with known acute toxicity but limited or no information on sublethal toxic...

  11. CATEGORICAL REGRESSION ANALYSIS OF ACUTE INHALATION TOXICITY DATA FOR HYDROGEN SULFIDE

    EPA Science Inventory

    Categorical regression is one of the tools offered by the U.S. EPA for derivation of acute reference exposures (AREs), which are dose-response assessments for acute exposures to inhaled chemicals. Categorical regression is used as a meta-analytical technique to calculate probabi...

  12. Acute Appendicitis Secondary to Acute Promyelocytic Leukemia

    PubMed Central

    Rodriguez, Eduardo A.; Lopez, Marvin A.; Valluri, Kartik; Wang, Danlu; Fischer, Andrew; Perdomo, Tatiana

    2015-01-01

    Patient: Female, 43 Final Diagnosis: Myeloid sarcoma appendicitis Symptoms: Abdominal pain • chills • fever Medication: — Clinical Procedure: Laparoscopic appendectomy, bone marrow biopsy Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: The gastrointestinal tract is a rare site for extramedullary involvement in acute promyelocytic leukemia (APL). Case Report: A 43-year-old female with no past medical history presented complaining of mild abdominal pain, fever, and chills for the past day. On examination, she was tachycardic and febrile, with mild tenderness of her right lower quadrant and without signs of peritoneal irritation. Laboratory examination revealed pancytopenia and DIC, with a fibrinogen level of 290 mg/dL. CT of the abdomen showed a thickened and hyperemic appendix without perforation or abscess, compatible with acute appendicitis. The patient was given IV broad-spectrum antibiotics and was transfused with packed red blood cells and platelets. She underwent uncomplicated laparoscopic appendectomy and bone marrow biopsy, which revealed neo-plastic cells of 90% of the total bone marrow cellularity. Flow cytometry indicated presence of 92.4% of immature myeloid cells with t (15: 17) and q (22: 12) mutations, and FISH analysis for PML-RARA demonstrated a long-form fusion transcript, positive for APL. Appendix pathology described leukemic infiltration with co-expression of myeloperoxidase and CD68, consistent with myeloid sarcoma of the appendix. The patient completed a course of daunorubicin, cytarabine, and all trans-retinoic acid. Repeat bone marrow biopsy demonstrated complete remission. She will follow up with her primary care physician and hematologist/oncologist. Conclusions: Myeloid sarcoma of the appendix in the setting of APL is very rare and it might play a role in the development of acute appendicitis. Urgent management, including bone marrow biopsy for definitive diagnosis and urgent surgical intervention

  13. INTER-SPECIES MODELS FOR ACUTE AQUATIC TOXICITY BASED ON MECHANISM OF ACTION

    EPA Science Inventory

    This presentation will provide interspecies QSARs for acute toxicity to 17 aquatic species, such as fish, snail, tadpole, hydrozoan, crustacean, insect larvae, and bacteria developed using 5,000 toxic effect results for approximately 2400 chemicals.

  14. [Acute pancreatitis in children].

    PubMed

    Rottier, B L; Holl, R A; Draaisma, J M

    1998-02-21

    Acute pancreatitis is probably commoner in children than was previously thought. In children it is most commonly associated with trauma or viral infection. The presentation may be subtler than in adults, requiring a high index of suspicion in the clinician. In three children, two boys aged 4 and 10 and a girl of 15 years, acute pancreatitis was suspected because of the findings at ultrasonography and endoscopic retrograde cholangiopancreatography performed when the disease recurred (the boy aged 4), apathy and immobility without dehydration or other obvious causes (the boy aged 10), and severe abdominal pain in combination with vomiting (the girl). All three patients had severely increased (urinary) amylase levels. Most often, acute pancreatitis in children tends to be a self-limiting disease which responds well to conservative treatment. PMID:9562770

  15. Acute acalculous cholecystitis.

    PubMed

    Barie, Philip S; Eachempati, Soumitra R

    2003-08-01

    Acute cholecystitis can develop without gallstones in critically ill or injured patients. However, the development of acute acalculous cholecystitis is not limited to surgical or injured patients, or even to the intensive care unit. Diabetes, malignant disease, abdominal vasculitis, congestive heart failure, cholesterol embolization, and shock or cardiac arrest have been associated with acute acalculous cholecystitis. Children may also be affected, especially after a viral illness. The pathogenesis of acute acalculous cholecystitis is a paradigm of complexity. Ischemia and reperfusion injury, or the effects of eicosanoid proinflammatory mediators, appear to be the central mechanisms, but bile stasis, opioid therapy, positive-pressure ventilation, and total parenteral nutrition have all been implicated. Ultrasound of the gallbladder is the most accurate diagnostic modality in the critically ill patient, with gallbladder wall thickness of 3.5 mm or greater and pericholecystic fluid being the two most reliable criteria. The historical treatment of choice for acute acalculous cholecystitis has been cholecystectomy, but percutaneous cholecystostomy is now the mainstay of therapy, controlling the disease in about 85% of patients. Rapid improvement can be expected when the procedure is performed properly. The mortality rates (historically about 30%) for percutaneous and open cholecystostomy appear to be similar, reflecting the severity of illness, but improved resuscitation and critical care may portend a decreased risk of death. Interval cholecystectomy is usually not indicated after acute acalculous cholecystitis in survivors; if the absence of gallstones is confirmed and the precipitating disorder has been controlled, the cholecystostomy tube can be pulled out after the patient has recovered. PMID:12864960

  16. Acute Prevertebral Calcific Tendinitis

    PubMed Central

    Tamm, Alexander; Jeffery, Caroline C; Ansari, Khalid; Naik, Sandeep

    2015-01-01

    We present a case of neck pain in a middle-aged woman, initially attributed to a retropharyngeal infection and treated with urgent intubation. With the help of computed tomography, the diagnosis was later revised to acute prevertebral calcific tendinitis, a self-limiting condition caused by abnormal calcium hydroxyapatite deposition in the longus colli muscles. It is critical to differentiate between these two disease entities due to dramatic differences in management. A discussion of acute prevertebral calcific tendinitis and its imaging findings is provided below. PMID:27252789

  17. The Acute Abdominal Aorta.

    PubMed

    Mellnick, Vincent M; Heiken, Jay P

    2015-11-01

    Acute disorders of the abdominal aorta are potentially lethal conditions that require prompt evaluation and treatment. Computed tomography (CT) is the primary imaging method for evaluating these conditions because of its availability and speed. Volumetric CT acquisition with multiplanar reconstruction and three-dimensional analysis is now the standard technique for evaluating the aorta. MR imaging may be useful for select applications in stable patients in whom rupture has been excluded. Imaging is indispensable for diagnosis and treatment planning, because management has shifted toward endoluminal repair. Acute abdominal aortic conditions most commonly are complications of aneurysms and atherosclerosis. PMID:26526434

  18. Acute acalculous cholecystitis

    SciTech Connect

    Fox, M.S.; Wilk, P.J.; Weissmann, H.S.; Freeman, L.M.; Gliedman, M.L.

    1984-07-01

    Sixty-eight patients with acute acalculous cholecystitis were reviewed. The results of history and physical examinations were usually nondiagnostic. IDA cholescintigraphy (93 per cent accuracy rate) was the only reliable diagnostic modality. The results of oral cholecystography, intravenous cholangiography and ultrasonography were considerably less reliable. One-half of the patients had gangrenous cholecystitis. Cholecystectomy was the preferred operation with an over-all mortality of 9 per cent. IDA cholescintigraphy is an important new modality for the diagnosis of acute acalculous cholecystitis which, in the past, has often been difficult to diagnose.

  19. Acute Gynecologic Disorders.

    PubMed

    Donaldson, Carolyn K

    2015-11-01

    Premenopausal women with acute pelvic pain comprise a significant percentage of patients who present to the emergency room. Etiologies can be gynecologic, urologic, gastrointestinal, or vascular. Signs and symptoms are often nonspecific and overlapping. The choice of imaging modality is determined by the clinically suspected differential diagnosis. Ultrasound (US) is the preferred imaging modality for suspected obstetric or gynecologic disorders. CT is more useful when gastrointestinal or urinary tract pathology is likely. MR imaging is rarely used in the emergent setting, except to exclude appendicitis in pregnant women. This article presents a comprehensive review of imaging of acute gynecologic disorders. PMID:26526439

  20. Acute oral ulcers.

    PubMed

    Lehman, Julia S; Rogers, Roy S

    2016-01-01

    Accurate diagnosis of acute oral ulcers can be challenging. Important historic details include the pattern of recurrence, anatomic areas of involvement within the mouth and elsewhere on the mucocutaneous surface, associated medical symptoms or comorbidities, and symptomology. Careful mucocutaneous examination is essential. When necessary, biopsy at an active site without ulceration is generally optimal. Depending on the clinical scenario, supplemental studies that may be useful include cultures; perilesional biopsy for direct immunofluorescence testing; and evaluation for infectious diseases, gluten sensitivity, inflammatory bowel disease, human immunodeficiency virus infection, connective tissue diseases, or hematinic deficiencies. Clinicians should maintain a broad differential diagnosis when evaluating patients with acute oral ulcers. PMID:27343961

  1. Chemical sensors

    SciTech Connect

    Hubbard, C.W.; Gordon, R.L.

    1987-05-01

    The revolution in analytical chemistry promised by recent developments in the field of chemical sensors has potential for significant positive impact on both research and production activities conducted by and for the Department of Energy. Analyses which were, in the past, performed only with a roomful of expensive equipment can now be performed with miniature solid-state electronic devices or small optical probes. Progress in the development of chemical sensors has been rapid, and the field is currently growing at a great rate. In accordance, Pacific Northwest Laboratory initiated a survey of recent literature so that contributors to active programs in research on analytical methods could be made aware of principles and applications of this new technology. This report presents the results of that survey. The sensors discussed here are divided into three types: micro solid-state devices, optical sensors, and piezoelectric crystal devices. The report is divided into three corresponding sections. The first section, ''Micro Solid-State Devices,'' discusses the design, operation, and application of electronic sensors that are produced in much the same way as standard solid-state electronic devices. The second section, ''Optrodes,'' covers the design and operation of chemical sensors that use fiber optics to detect chemically induced changes in optical properties. The final section, ''Piezoelectric Crystal Detectors,'' discusses two types of chemical sensors that depend on the changes in the properties of an oscillating piezoelectric crystal to detect the presence of certain materials. Advantages and disadvantages of each type of sensor are summarized in each section.

  2. Chemical networks

    NASA Astrophysics Data System (ADS)

    Thi, Wing-Fai

    2015-09-01

    This chapter discusses the fundamental ideas of how chemical networks are build, their strengths and limitations. The chemical reactions that occur in disks combine the cold phase reactions used to model cold molecular clouds with the hot chemistry applied to planetary atmosphere models. With a general understanding of the different types of reactions that can occur, one can proceed in building a network of chemical reactions and use it to explain the abundance of species seen in disks. One on-going research subject is finding new paths to synthesize species either in the gas-phase or on grain surfaces. Specific formation routes for water or carbon monoxide are discussed in more details. 13th Lecture of the Summer School "Protoplanetary Disks: Theory and Modelling Meet Observations"

  3. What Is Acute Myeloid Leukemia?

    MedlinePlus

    ... about acute myeloid leukemia? What is acute myeloid leukemia? Cancer starts when cells in a part of ... the body from doing their jobs. Types of leukemia Not all leukemias are the same. There are ...

  4. INTERSPECIES CORRELATION ESTIMATIONS: ACUTE TOXICITY TO AQUATIC ORGANISMS

    EPA Science Inventory

    Predictive toxicological models, including estimates of uncertainty, are necessary to address the trend towards probability-based ecological risk assessments. A method and software were developed to aid in estimating acute toxicity of chemicals to species where data is lacking, p...

  5. Acute Neuroactive Drug Exposures alter Locomotor Activity in Larval Zebrafish

    EPA Science Inventory

    As part of the development of a rapid in vivo screen for prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae by assessing the acute effects of prototypic drugs that act on the central nervous system. Initially,...

  6. Nutrition, Inflammation, and Acute Pancreatitis

    PubMed Central

    Petrov, Max

    2013-01-01

    Acute pancreatitis is acute inflammatory disease of the pancreas. Nutrition has a number of anti-inflammatory effects that could affect outcomes of patients with pancreatitis. Further, it is the most promising nonspecific treatment modality in acute pancreatitis to date. This paper summarizes the best available evidence regarding the use of nutrition with a view of optimising clinical management of patients with acute pancreatitis. PMID:24490104

  7. Acute Septic Arthritis

    PubMed Central

    Shirtliff, Mark E.; Mader, Jon T.

    2002-01-01

    Acute septic arthritis may develop as a result of hematogenous seeding, direct introduction, or extension from a contiguous focus of infection. The pathogenesis of acute septic arthritis is multifactorial and depends on the interaction of the host immune response and the adherence factors, toxins, and immunoavoidance strategies of the invading pathogen. Neisseria gonorrhoeae and Staphylococcus aureus are used in discussing the host-pathogen interaction in the pathogenesis of acute septic arthritis. While diagnosis rests on isolation of the bacterial species from synovial fluid samples, patient history, clinical presentation, laboratory findings, and imaging studies are also important. Acute nongonococcal septic arthritis is a medical emergency that can lead to significant morbidity and mortality. Therefore, prompt recognition, rapid and aggressive antimicrobial therapy, and surgical treatment are critical to ensuring a good prognosis. Even with prompt diagnosis and treatment, high mortality and morbidity rates still occur. In contrast, gonococcal arthritis is often successfully treated with antimicrobial therapy alone and demonstrates a very low rate of complications and an excellent prognosis for full return of normal joint function. In the case of prosthetic joint infections, the hardware must be eventually removed by a two-stage revision in order to cure the infection. PMID:12364368

  8. Acute coronary care 1986

    SciTech Connect

    Califf, R.M.; Wagner, G.S.

    1985-01-01

    This book contains 22 chapters. Some of the titles are: The measurement of acute myocardial infarct size by CT; Magnetic resonance imaging for evaluation of myocardial ischemia and infarction; Poistron imaging in the evaluation of ischemia and myocardial infarction; and New inotropic agents.

  9. Acute radiation risk models

    NASA Astrophysics Data System (ADS)

    Smirnova, Olga

    Biologically motivated mathematical models, which describe the dynamics of the major hematopoietic lineages (the thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems) in acutely/chronically irradiated humans are developed. These models are implemented as systems of nonlinear differential equations, which variables and constant parameters have clear biological meaning. It is shown that the developed models are capable of reproducing clinical data on the dynamics of these systems in humans exposed to acute radiation in the result of incidents and accidents, as well as in humans exposed to low-level chronic radiation. Moreover, the averaged value of the "lethal" dose rates of chronic irradiation evaluated within models of these four major hematopoietic lineages coincides with the real minimal dose rate of lethal chronic irradiation. The demonstrated ability of the models of the human thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems to predict the dynamical response of these systems to acute/chronic irradiation in wide ranges of doses and dose rates implies that these mathematical models form an universal tool for the investigation and prediction of the dynamics of the major human hematopoietic lineages for a vast pattern of irradiation scenarios. In particular, these models could be applied for the radiation risk assessment for health of astronauts exposed to space radiation during long-term space missions, such as voyages to Mars or Lunar colonies, as well as for health of people exposed to acute/chronic irradiation due to environmental radiological events.

  10. [Acute pancreatitis and pregnancy].

    PubMed

    Scollo, P; Licitra, G

    1993-12-01

    Aetiologic factors (gallstones, hyperlipidemia I-IV, hypertriglyceridaemia) make their occurrence, mainly, in the third trimester of gestation. Two cases of acute pancreatitis in pregnancy are described; in both cases patients referred healthy diet, no habit to smoke and no previous episode of pancreatitis. An obstructive pathology of biliary tract was the aetiologic factor. Vomiting, upper abdominal pain are aspecific symptoms that impose a differential diagnosis with acute appendicitis, cholecystitis and obstructive intestinal pathology. Laboratory data (elevated serum amylase and lipase levels) and ultrasonography carry out an accurate diagnosis. The management of acute pancreatitis is based on the use of symptomatic drugs, a low fat diet alternated to the parenteral nutrition when triglycerides levels are more than 28 mmol/L. Surgical therapy, used only in case of obstructive pathology of biliary tract, is optimally collected in the third trimester or immediately after postpartum. Our patients, treated only medically, delivered respectively at 38th and 40th week of gestation. Tempestivity of diagnosis and appropriate therapy permit to improve prognosis of a pathology that, although really associated with pregnancy, presents high maternal mortality (37%) cause of complications (shock, coagulopathy, acute respiratory insufficiency) and fetal (37.9%) by occurrence of preterm delivery. PMID:8139793

  11. [Acute blood pressure elevations].

    PubMed

    Chamontin, B; Amar, J; Chollet, F; Rouge, P; Bonetti-d'Esteve, L; Guittard, J; Salvador, M

    2000-11-01

    Blood pressure (BP) elevations may correspond to different clinical situations. Hypertensives emergencies are situations that require immediate reduction in BP because of acute or rapidly progressing target organ damage: accelerated malignant hypertension, hypertensive encephalopathy, acute myocardial infarction, acute aortic dissection, acute left ventricular failure, and eclampsia. Hypertensive urgencies are those with marked elevated BP in which it is desirable to reduce BP progressively within few hours, such as severe hypertension, progressive target organ damage, perioperative hypertension. Cerebrovascular accidents have to be individualized. In most patients in the immediate post-stroke period, BP should not be lowered. Caution is advised in lowering BP in these patients because excessive falls may precipitate cerebral ischemia. In situations without symptoms or progressive target organ it is necessary to exclude proximate causes of elevated BP such as pain and elevated BP alone rarely requires antihypertensive treatment. Among parenteral antihypertensive (AH) drugs labetalol, nicardipine, urapidil, and nitroprussiate are generally used, and the choice of AH drug depends on the clinical situation. It is not required to normalize BP immediately but to reduce mean BP no more than 25%, then toward 160/100 mmHg as recommended by JNC VI, in order to avoid an impairment of renal, cerebral or coronary ischemia. Oral long-acting dihydropyridines are often subsequently administrated, except in myocardial ischemia. Therapeutic attitudes vary considerably according to the clinical situation: abstention, immediate decrease or progressive decrease in BP have to be decided. PMID:11190294

  12. Gadolinium induced recurrent acute pancreatitis.

    PubMed

    Blasco-Perrin, H; Glaser, B; Pienkowski, M; Peron, J M; Payen, J L

    2013-01-01

    Acute pancreatitis is a sudden swelling and inflammation of the pancreas. The two most common causes are alcohol use and biliary stones. Drug-induced acute pancreatitis are rare (1.4-2%). In this present study, we present a case of recurrent acute pancreatitis induced by a specific magnetic-resonance-imaging (MRI) contrast agent called gadobenate dimeglumine. PMID:23395575

  13. Acute hepatitis E complicated by acute pancreatitis and multiorgan dysfunction

    PubMed Central

    Karanth, Suman S; Khan, Zohaib; Rau, Nileshwar Radhakrishna; Rao, Karthik

    2014-01-01

    We report this rare case of a 27-year-old man who presented with acute hepatitis E and went on to develop acute epigastric pain. He was diagnosed to have acute severe pancreatitis with shock and acute renal failure due to hepatitis E. Such a phenomenon has rarely been reported in the literature, with patients following a benign course and complete recovery after conservative management and analgesia. Awareness of this potentially life-threatening complication, especially in young men from endemic areas with acute hepatitis E presenting with abdomen pain has been highlighted. PMID:24899005

  14. Delicious Chemicals.

    ERIC Educational Resources Information Center

    Barry, Dana M.

    This paper presents an approach to chemistry and nutrition that focuses on food items that people consider delicious. Information is organized according to three categories of food chemicals that provide energy to the human body: (1) fats and oils; (2) carbohydrates; and (3) proteins. Minerals, vitamins, and additives are also discussed along with…

  15. Chemical sensors

    SciTech Connect

    Janata, J.; Josowicz, M.; DeVaney, D.M. )

    1994-06-15

    This review of chemical sensors contains the following topics of interest: books and reviews; reviews of sensors by their type; fabrication and selectivity; data processing; thermal sensors; mass sensors (fabrication, gas sensors, and liquid sensors); electrochemical sensors (potentiometric sensors, amperometric sensors, and conductometric sensors); and optical sensors (fabrication, liquid sensors, biosensors, and gas sensors). 795 refs., 1 tab.

  16. Chemical Mahjong

    ERIC Educational Resources Information Center

    Cossairt, Travis J.; Grubbs, W. Tandy

    2011-01-01

    An open-access, Web-based mnemonic game is described whereby introductory chemistry knowledge is tested using mahjong solitaire game play. Several tile sets and board layouts are included that are themed upon different chemical topics. Introductory tile sets can be selected that prompt the player to match element names to symbols and metric…

  17. Unfavourable results in acute burn management

    PubMed Central

    Bilwani, P. K.

    2013-01-01

    An etiology based classification has been devised to innumerate all possible unfavorable results (complications) which may occur during acute burn management. Various factors, right from the onset of burns, may affect the final outcome. These factors, starting from the onset of burns till the occurrence of complication, have been discussed in details. Unfavorable results in regional burns (chest, limb, eye, ear, and hand) have been discussed. Unfavorable results in various chemical burns have been described with necessary precautions to prevent. Various septic complications have been narrated and their prevention is also discussed. PMID:24501478

  18. Acute gangrenous cholecystitis: radionuclide diagnosis

    SciTech Connect

    Brachman, M.B.; Tanasescu, D.E.; Ramanna, L.; Waxman, A.D.

    1984-04-01

    Radionuclide hepatobiliary imaging with Tc-99m IDA is a useful procedure for the diagnosis of acute cholecystitis. Visualization of the gallbladder essentially rules out acute cholecystitis. Nonvisualization suggest acute cholecystitis but may also be associated with chronic gallbladder disease or other conditions. The authors recently observed five patients in whom a rim of increased parenchymal liver activity was seen adjacent to the gallbladder fossa. All five patients had acute gangrenous cholecystitis. The rim of increased activity appears to be a useful secondary sign of acute cholecystitis.

  19. Severe Acute Pancreatitis in Pregnancy

    PubMed Central

    Abdullah, Bahiyah; Kathiresan Pillai, Thanikasalam; Cheen, Lim Huay; Ryan, Ray Joshua

    2015-01-01

    This is a case of a pregnant lady at 8 weeks of gestation, who presented with acute abdomen. She was initially diagnosed with ruptured ectopic pregnancy and ruptured corpus luteal cyst as the differential diagnosis. However she then, was finally diagnosed as acute hemorrhagic pancreatitis with spontaneous complete miscarriage. This is followed by review of literature on this topic. Acute pancreatitis in pregnancy is not uncommon. The emphasis on high index of suspicion of acute pancreatitis in women who presented with acute abdomen in pregnancy is highlighted. Early diagnosis and good supportive care by multidisciplinary team are crucial to ensure good maternal and fetal outcomes. PMID:25628906

  20. ESTIMATING ACUTE AND CRONIC TOXICITY OF CHEMICALS FOR ENDANGERED FISHES

    EPA Science Inventory

    Predictive toxicological models, including estimates of uncertainty, are necessary to perform probability-based ecological risk assessments. This is particularly true for the protection of endangered species that are not prudent to test, other species that have not been tested o...

  1. Chemical composition of rainbow trout urine following acute hypoxic stress

    USGS Publications Warehouse

    Hunn, Joseph B.

    1969-01-01

    Rainbow trout (Salmo gairdnerii) were anesthetized with MS-222, catheterized, and introduced into urine collecting chambers. Twenty-four hours after introduction, a 4-hour accumulation of urine was collected to serve as the control. Water flow to the chambers was then discontinued for 30 minutes during which the oxygen content of the water exiting in the chamber dropped from 4.9 to 2.8 mg/l. Following this hypoxic stress fresh water was restored and accumulated urine samples were taken for analysis at 1, 4, and 20 hours post-hypoxic stress. Rainbow trout excrete abnormally high concentrations of Na, K, Mg, Cl, and inorganic PO4 following hypoxia.

  2. Acute chylous ascites mimicking acute appendicitis in a patient with pancreatitis

    PubMed Central

    Smith, Emily K; Ek, Edmund; Croagh, Daniel; Spain, Lavinia A; Farrell, Stephen

    2009-01-01

    We report a case of acute chylous peritonitis mimicking acute appendicitis in a man with acute on chronic pancreatitis. Pancreatitis, both acute and chronic, causing the development of acute chylous ascites and peritonitis has rarely been reported in the English literature. This is the fourth published case of acute chylous ascites mimicking acute appendicitis in the literature. PMID:19824123

  3. Chemical warfare

    PubMed Central

    Samuels, Richard Ian; Mattoso, Thalles Cardoso; Moreira, Denise D.O.

    2013-01-01

    Leaf-cutting ants are well known for their highly complex social organization, which provides them with a strong defense against parasites invading their colonies. Besides this attribute, these insects have morphological, physiological and structural characteristics further reinforcing the defense of their colonies. With the discovery of symbiotic bacteria present on the integument of leaf-cutting ants, a new line of defense was proposed and considered to be specific for the control of a specialized fungal parasite of the ants’ fungus gardens (Escovopsis). However, recent studies have questioned the specificity of the integumental bacteria, as they were also found to inhibit a range of fungi, including entomopathogens. The microbiota associated with the leaf-cutting ant gardens has also been proposed as another level of chemical defense, protecting the garden from parasite invasion. Here we review the chemical defense weaponry deployed by leaf-cutting ants against parasites of their fungus gardens and of the ants themselves. PMID:23795235

  4. Acute Heart Failure Treatment.

    PubMed

    Levy, Phillip D; Bellou, Abdel

    2013-06-01

    Dyspnea is the predominant symptom for patients with acute heart failure and initial treatment is largely directed towards the alleviation of this. Contrary to conventional belief, not all patients present with fluid overload and the approach to management is rapidly evolving from a solitary focus on diuresis to one that more accurately reflects the complex interplay of underlying cardiac dysfunction and acute precipitant. Effective treatment thus requires an understanding of divergent patient profiles and an appreciation of various therapeutic options for targeted patient stabilization. The key principle within this paradigm is directed management that aims to diminish the work of breathing through situation appropriate ventillatory support, volume reduction and hemodynamic improvement. With such an approach, clinicians can more efficiently address respiratory discomfort while reducing the likelihood of avoidable harm. PMID:24223323

  5. Acute Biliary Septic Shock

    PubMed Central

    1990-01-01

    Forty-seven cases of biliary tract infection with septic shock are presented. The sepsis was caused by empyema of the gallbladder in 23 cases and by cholangitis in the remainder. Gallstones were most frequently the cause of the sepsis. An appropriate diagnostic description of the syndrome of biliary tract infection and septic shock should therefore include a description of the underlying biliary disease as well as the term acute biliary shock. In this series, emergency surgical management by removal of gallstones and drainage of suppuration was felt to be the most appropriate treatment. There was a high incidence of gallbladder rupture (10.6%) and intrahepatic stones (53.2%). Of the 13 patients who died, 8 might have survived if early operation had been performed after the diagnosis of acute biliary septic shock was established. PMID:2278914

  6. Acute aortic syndrome

    PubMed Central

    2016-01-01

    Acute aortic syndrome (AAS) is a term used to describe a constellation of life-threatening aortic diseases that have similar presentation, but appear to have distinct demographic, clinical, pathological and survival characteristics. Many believe that the three major entities that comprise AAS: aortic dissection (AD), intramural hematoma (IMH) and penetrating aortic ulcer (PAU), make up a spectrum of aortic disease in which one entity may evolve into or coexist with another. Much of the confusion in accurately classifying an AAS is that they present with similar symptoms: typically acute onset of severe chest or back pain, and may have similar radiographic features, since the disease entities all involve injury or disruption of the medial layer of the aortic wall. The accurate diagnosis of an AAS is often made at operation. This manuscript will attempt to clarify the similarities and differences between AD, IMH and PAU of the ascending aorta and describe the challenges in distinguishing them from one another. PMID:27386405

  7. [Acute aortic syndrome].

    PubMed

    Nienaber, Christoph A

    2016-06-01

    Acute aortic syndrome is the common denominator for acute events to the aortic wall and encompasses dissection of the aorta, intramural hematoma, formation of aortic ulcers and trauma to the aorta with an annual incidence of up to 35 cases/100.000 between 65 and 75 years of age. Both, inflammation and/or microtrauma at the level of the aortic media layer, and a genetic disposition are promoting elements of AAS, while the extent and anatomic involvement of the ascending aorta call for either surgical resection/repair in the proximal part of the aorta, or an endovascular solution for pathologies in the distal aorta; in all cases of dissection (regardless of location) reconstruction/realignment has been proven to portend better long-term outcomes (in addition to medical management of blood pressure). PMID:27254622

  8. Acute aortic syndrome.

    PubMed

    Corvera, Joel S

    2016-05-01

    Acute aortic syndrome (AAS) is a term used to describe a constellation of life-threatening aortic diseases that have similar presentation, but appear to have distinct demographic, clinical, pathological and survival characteristics. Many believe that the three major entities that comprise AAS: aortic dissection (AD), intramural hematoma (IMH) and penetrating aortic ulcer (PAU), make up a spectrum of aortic disease in which one entity may evolve into or coexist with another. Much of the confusion in accurately classifying an AAS is that they present with similar symptoms: typically acute onset of severe chest or back pain, and may have similar radiographic features, since the disease entities all involve injury or disruption of the medial layer of the aortic wall. The accurate diagnosis of an AAS is often made at operation. This manuscript will attempt to clarify the similarities and differences between AD, IMH and PAU of the ascending aorta and describe the challenges in distinguishing them from one another. PMID:27386405

  9. Acute Ischemic Stroke Intervention.

    PubMed

    Khandelwal, Priyank; Yavagal, Dileep R; Sacco, Ralph L

    2016-06-01

    Acute ischemic stroke (AIS) is the leading cause of disability worldwide and among the leading causes of mortality. Although intravenous tissue plasminogen activator (IV-rtPA) was approved nearly 2 decades ago for treatment of AIS, only a minority of patients receive it due to a narrow time window for administration and several contraindications to its use. Endovascular approaches to recanalization in AIS developed in the 1980s, and recently, 5 major randomized trials showed an overwhelming superior benefit of combining endovascular mechanical thrombectomy with IV-rtPA over IV-rtPA alone. In this paper, we discuss the evolution of catheter-based treatment from first-generation thrombectomy devices to the game-changing stent retrievers, results from recent trials, and the evolving stroke systems of care to provide timely access to acute stroke intervention to patients in the United States. PMID:27256835

  10. [Acute Chest Pain].

    PubMed

    Gmür, Christian

    2016-02-17

    Acute chest pain is a frequent consultation reason in general practice as well as in emergency departments. With the help of history, physical examination, ECG, laboratory and newly developed risk scores, potentially life-threatening diseases and high-risk patients may be detected and treated early, quickly and cost-effectively. New biomarkers and their combination with risk scores can increase the negative predictive value to exclude certain diseases. PMID:26886697

  11. Diarrhoea in adults (acute)

    PubMed Central

    2008-01-01

    Introduction An estimated 4000 million cases of diarrhoea occurred worldwide in 1996, resulting in 2.5 million deaths. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute diarrhoea in adults living in resource-rich countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries traveling to resource-poor countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults living in resource-poor countries? What are the effects of treatments for acute severe diarrhoea in adults living in resource-poor countries? We searched: Medline, Embase, The Cochrane Library and other important databases up to January 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, antimotility agents, antisecretory agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube rehydration, and oral rehydration solutions (amino acid oral rehydration solution, bicarbonate oral rehydration solution, reduced osmolarity oral rehydration solution, rice-based oral rehydration solution, standard oral rehydration solution). PMID:19450323

  12. Diarrhoea in adults (acute)

    PubMed Central

    2011-01-01

    Introduction An estimated 4.6 billion cases of diarrhoea occurred worldwide in 2004, resulting in 2.2 million deaths. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute diarrhoea in adults living in resource-rich countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries travelling to resource-poor countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults living in resource-poor countries? What are the effects of treatments for acute severe diarrhoea in adults living in resource-poor countries? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 72 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, antimotility agents, antisecretory agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube rehydration, oral rehydration solutions (amino acid oral rehydration solution, bicarbonate oral rehydration solution, reduced osmolarity oral rehydration solution, rice-based oral rehydration solution, standard oral rehydration solution), vitamin A supplementation, and zinc supplementation. PMID:21718555

  13. Acupuncture for acute hordeolum

    PubMed Central

    Cheng, Ke; Wang, Xue; Guo, Menghu; Wieland, L. Susan; Shen, Xueyong; Lao, Lixing

    2014-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: The objective of this review is to determine the effects and, when possible, the safety of acupuncture for the treatment of acute hordeola, in comparison to no specific treatment (e.g., observation), sham acupuncture, or other active treatments. Acupuncture as an adjuvant to another treatment also will be compared to that treatment alone. PMID:25214814

  14. IMMUNOTHERAPY IN ACUTE LEUKEMIA

    PubMed Central

    Leung, Wing

    2010-01-01

    Recent advances in immunotherapy of cancer may represent a successful example in translational research, in which progress in knowledge and technology in immunology has lead to new strategies of immunotherapy, and even past failure in many clinical trials have led to a better understanding of basic cancer immunobiology. This article reviews the latest concepts in antitumor immunology and its application in the treatment of cancer, with particular focus on acute leukemia. PMID:19100371

  15. Streptococcal acute pharyngitis.

    PubMed

    Anjos, Lais Martins Moreira; Marcondes, Mariana Barros; Lima, Mariana Ferreira; Mondelli, Alessandro Lia; Okoshi, Marina Politi

    2014-07-01

    Acute pharyngitis/tonsillitis, which is characterized by inflammation of the posterior pharynx and tonsils, is a common disease. Several viruses and bacteria can cause acute pharyngitis; however, Streptococcus pyogenes (also known as Lancefield group A β-hemolytic streptococci) is the only agent that requires an etiologic diagnosis and specific treatment. S. pyogenes is of major clinical importance because it can trigger post-infection systemic complications, acute rheumatic fever, and post-streptococcal glomerulonephritis. Symptom onset in streptococcal infection is usually abrupt and includes intense sore throat, fever, chills, malaise, headache, tender enlarged anterior cervical lymph nodes, and pharyngeal or tonsillar exudate. Cough, coryza, conjunctivitis, and diarrhea are uncommon, and their presence suggests a viral cause. A diagnosis of pharyngitis is supported by the patient's history and by the physical examination. Throat culture is the gold standard for diagnosing streptococcus pharyngitis. However, it has been underused in public health services because of its low availability and because of the 1- to 2-day delay in obtaining results. Rapid antigen detection tests have been used to detect S. pyogenes directly from throat swabs within minutes. Clinical scoring systems have been developed to predict the risk of S. pyogenes infection. The most commonly used scoring system is the modified Centor score. Acute S. pyogenes pharyngitis is often a self-limiting disease. Penicillins are the first-choice treatment. For patients with penicillin allergy, cephalosporins can be an acceptable alternative, although primary hypersensitivity to cephalosporins can occur. Another drug option is the macrolides. Future perspectives to prevent streptococcal pharyngitis and post-infection systemic complications include the development of an anti-Streptococcus pyogenes vaccine. PMID:25229278

  16. [Acute coronary syndromes: epidemiology].

    PubMed

    Ozkan, Alev Arat

    2013-04-01

    Coronary heart disease is the main cause of death in the world as well as in Turkey. It's not only a health issue but also a social problem with a high economic burden and negative impact on quality of life. The majority of deaths are attributable to acute coronary syndromes (ACS) and their complications.This review summarizes some important facts regarding ACS epidemiology in the world and in Turkey. PMID:27323430

  17. Acute inhalation toxicity testing: considerations of technical and regulatory aspects.

    PubMed

    Pauluhn, J; Bury, D; Föst, U; Gamer, A; Hoernicke, E; Hofmann, T; Kunde, M; Neustadt, T; Schlede, E; Schnierle, H; Wettig, K; Westphal, D

    1996-01-01

    The EU regulatory statute for the acute hazard identification of chemicals requires selection of the two most appropriate routes of administration. Testing employing the oral route is mandatory, whereas selection of the dermal or inhalation route requires expert judgement, i.e. considerations of structural alerts with regard to the inherent acute inhalation toxicity as well as the likelihood of dermal and inhalation exposure, respectively. Currently, testing of chemicals requires acute inhalation exposure of 4-h and 1-h durations according the EU classification and labelling and UN Transport Guidelines, respectively. The analysis made revealed that 1-h exposures appear to add little knowledge in addition to existing 4-h LC50 values and a default value of 4 should be used for conversion of 4-h to 1-h LC50 values, independently of the physical state of the chemical. Therefore, also the unit of concentration of exposure atmospheres should be independent of nominal features of the test substance. Hence, the preferred dose metric is mass (mg/liter air) rather than volume (ppm). Taking into account the overall variability of acute toxicity data the recommendations given are classification into the following groups of 4-h LC50 values: < or = 0.05, > 0.05-0.2, > 0.2-1, > 1-5 and > 5.0 mg/l. No distinction should be made concerning vapours and aerosols with regard to units and conversion factors from 4-h to 1-h LC50 values and the default factor of 4 appears to be most suitable. Further differentiation of classification is not indicated due to technical variability of acute inhalation testing and resolution of the acute bioassay. PMID:9010579

  18. Acute tubulointerstitial nephritis.

    PubMed

    Ulinski, Tim; Sellier-Leclerc, Anne-Laure; Tudorache, Elena; Bensman, Albert; Aoun, Bilal

    2012-07-01

    Acute tubulointerstitial nephritis (TIN) is a frequent cause of acute renal failure, characterised by the presence of inflammatory cell infiltrate in the interstitium of the kidney. Immuno-allergic reaction to certain medications, mainly non-steroidal anti-inflammatory drugs and antibiotics are by far the most important etiology for TIN today, but other situations such as infections, toxins, and vasculitis are known to induce TIN. Incidence of TIN is increasing, probably due to prescription habits and NSAID overuse, representing 3-7% of acute kidney injury in biopsies in children. Avoidance of the causal substance and rapid steroid therapy are hallmarks for patient care, but spontaneous initial recovery is very frequent and the general prognosis seems satisfactory. However, development of chronic TIN, without response to steroid or other immunosuppressive treatment, is possible. As the largest part of TIN is secondary to certain drugs, clear indications in particular for NSAID or antibiotics should be respected to reduce the number of TIN cases. PMID:21638156

  19. Acute lung injury review.

    PubMed

    Tsushima, Kenji; King, Landon S; Aggarwal, Neil R; De Gorordo, Antonio; D'Alessio, Franco R; Kubo, Keishi

    2009-01-01

    The first report of acute respiratory distress syndrome (ARDS) was published in 1967, and even now acute lung injury (ALI) and ARDS are severe forms of diffuse lung disease that impose a substantial health burden all over the world. Recent estimates indicate approximately 190,000 cases per year of ALI in the United States each year, with an associated 74,500 deaths per year. Common causes of ALI/ARDS are sepsis, pneumonia, trauma, aspiration pneumonia, pancreatitis, and so on. Several pathologic stages of ALI/ARDS have been described: acute inflammation with neutrophil infiltration, fibroproliferative phase with hyaline membranes, with varying degrees of interstitial fibrosis, and resolution phase. There has been intense investigation into the pathophysiologic events relevant to each stage of ALI/ARDS, and much has been learned in the alveolar epithelial, endobronchial homeostasis, and alveolar cell immune responses, especially neutrophils and alveolar macrophages in an animal model. However, these effective results in the animal models are not equally adoptive to those in randomized, controlled trials. The clinical course of ALI/ARDS is variable with the likely pathophysiologic complexity of human ALI/ARDS. In 1994, the definition was recommended by the American-European Consensus Conference Committee, which facilitated easy nomination of patients with ALI/ARDS for a randomized, clinical trial. Here, we review the recent randomized, clinical trials of ALI/ARDS. PMID:19420806

  20. Isocyanates and respiratory disease: current status

    SciTech Connect

    Musk, A.W.; Peters, J.M.; Wegman, D.H.

    1988-01-01

    This paper reviews the known respiratory effects of isocyanates. There is good evidence to indicate that isocyanates: cause chemical bronchitis/pneumonitis; are potent pulmonary sensitizers capable of causing isocyanate asthma; cause nonspecific airways disease, including chronic bronchitis; can induce a general asthmatic state; and can cause hypersensitivity pneumonitis. Similar dose-response relationships are seen for both acute and chronic effects. There are plants operating in which exposures are well controlled and in which no respiratory effects can be detected. Suggestions are provided for preplacement assessment and periodic surveillance for workers exposed to these compounds.114 references.