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Sample records for hypersensitivity pneumonitis correlation

  1. 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 . ...

  2. 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 ...

  3. 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

  4. 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.

  5. Chronic hypersensitivity pneumonitis

    PubMed Central

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

    2016-01-01

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

  6. Mold-induced hypersensitivity pneumonitis.

    PubMed

    Greenberger, Paul A

    2004-01-01

    Mold-induced hypersensitivity pneumonitis results from macrophage- and lymphocyte-driven inflammation, which may be attributable to contaminated humidifiers or heating-ventilation systems or sources in homes, schools, or workplaces. A case may be suspected when there is water intrusion or inadequate drainage. Some fungal causes include species of Alternaria, Aspergillus, Cryptostroma, Penicillium, Pullularia, Rhodotorula, and Trichosporon. The differential diagnosis includes mold-induced asthma, sick building syndrome, mass psychogenic illness (epidemic hysteria), unjustified fears of "toxic" molds, and conditions causing recurrent pneumonitis. PMID:15510579

  7. Hypersensitivity pneumonitis during minocycline treatment.

    PubMed

    Kloppenburg, M; Dijkmans, B A; Breedveld, F C

    1994-06-01

    A patient is reported who developed dyspnoea, fever, pleuritic chest pain and a non-productive cough following treatment with minocycline for 9 days. The chest radiograph showed an interstitial pattern and there was a peripheral eosinophilia. A diagnosis of hypersensitivity pneumonitis attributable to minocycline was made. The disease responded quickly to withdrawal of the drug. This observation shows that minocycline, despite its mild toxicity profile, can give rise to serious adverse effects.

  8. 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

  9. 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.

  10. Recent advances in hypersensitivity pneumonitis.

    PubMed

    Lacasse, Yves; Girard, Mélissa; Cormier, Yvon

    2012-07-01

    Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an allergen to which the subject has been previously sensitized. The diagnosis of HP most often relies on an array of nonspecific clinical symptoms and signs developed in an appropriate setting, with the demonstration of interstitial markings on chest radiographs, serum precipitating antibodies against offending antigens, a lymphocytic alveolitis on BAL, and/or a granulomatous reaction on lung biopsies. The current classification of HP in acute, subacute, and chronic phases is now challenged, and a set of clinical predictors has been proposed. Nonspecific interstitial pneumonitis, usual interstitial pneumonia, and bronchiolitis obliterans organizing pneumonia may be the sole histologic expression of the disease. Presumably, like in idiopathic interstitial pneumonia, acute exacerbations of chronic HP may occur without further exposure to the offending antigen. New offending antigens, such as mycobacteria causing hot tub lung and metalworking fluid HP, have recently been identified and have stimulated further research in HP. PMID:22796841

  11. Lung Transplantation for Hypersensitivity Pneumonitis

    PubMed Central

    Singer, Jonathan P.; Koth, Laura; Mooney, Joshua; Golden, Jeff; Hays, Steven; Greenland, John; Wolters, Paul; Ghio, Emily; Jones, Kirk D.; Leard, Lorriana; Kukreja, Jasleen; Blanc, Paul D.

    2015-01-01

    BACKGROUND: Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF). METHODS: To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling. RESULTS: We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts. CONCLUSIONS: Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft. PMID:25412059

  12. Hydrocodone snorting leading to hypersensitivity pneumonitis.

    PubMed

    Pathak, Lakshmi Kant; Vijayaraghavan, Vimala

    2016-07-01

    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

  13. 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

  14. Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria

    PubMed Central

    Beckett, William; Kallay, Michael; Sood, Akshay; Zuo, Zhengfa; Milton, Donald

    2005-01-01

    A previously healthy man working as a machine operator in an automotive factory developed respiratory symptoms. Medical evaluation showed abnormal pulmonary function tests, a lung biopsy showed hypersensitivity pneumonitis, and his illness was traced to his work environment. His physician asked the employer to remove him from exposure to metalworking fluids. Symptoms reoccurred when he was later reexposed to metalworking fluids, and further permanent decrement in his lung function occurred. Investigation of his workplace showed that five of six large reservoirs of metalworking fluids (cutting oils) grew Mycobacterium chelonae (or Mycobacterium immunogenum), an organism previously associated with outbreaks of hypersensitivity pneumonitis in automaking factories. His lung function remained stable after complete removal from exposure. The employer, metalworking fluid supplier, union, and the National Institute for Occupational Safety and Health were notified of this sentinel health event. No further cases have been documented in this workplace. PMID:15929902

  15. [A misleading form of hypersensitivity pneumonitis].

    PubMed

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

    2000-11-01

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

  16. [Hypersensitivity pneumonitis after exposure to Candida spp].

    PubMed

    Serrano, Carlos; Torrego, Alfonso; Loosli, Alfonso; Valero, Antonio; Picado, César

    2010-05-01

    Hypersensitivity pneumonitis (HP) is a lung disease caused by heavy and recurrent inhalation of antigens. We describe the case of a patient with HP caused by domestic exposure to Candida spp. The diagnosis was made by taking into consideration the, clinical presentation, exposure history, radiological findings, bronchoalveolar lavage, lung function and the immuno-allergy study. The diagnosis was definitively confirmed by performing a specific bronchial provocation test. It has been shown that there is cross-reactivity between different Candida species, and despite making the diagnosis in this case with Candida albicans, we were unable to define exactly which species was responsible for the HP.

  17. Hypersensitivity pneumonitis related to medium-density fiberboard.

    PubMed

    Toribio, Ramón; Cruz, María Jesús; Morell, Ferran; Muñoz, Xavier

    2012-01-01

    Pneumonitis due to hypersensitivity to wood fiber is mainly associated with the fungus that colonizes it. We present the case of a male affected with hypersensitivity pneumonitis in which the agent implicated was medium-density fiberboard, an engineered product whose main component is pine wood fiber. The causal agent was identified by means of a specific bronchial provocation test.

  18. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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...

  19. 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...

  20. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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...

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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...

  3. 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

  4. 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

  5. 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.

  6. Application of hypersensitivity skin testing in chemotherapy-induced pneumonitis

    PubMed Central

    Kuo, James C; Hawkins, Carolyn A

    2015-01-01

    Skin testing has been utilised to determine the culprit allergenic agent in drug reactions. Its application in the setting of hypersensitivity reaction relating to combination chemotherapeutic regimens may help identify the causative drug, allowing drug that is safe to be continued and avoiding limiting treatment options for patients. We report what we believe to be the first published case of hypersensitivity skin testing for gemcitabine-induced pneumonitis in a patient with metastatic leiomyosarcoma and another case of docetaxel-induced pneumonitis in a patient with metastatic HER2-positive breast cancer. PMID:26539407

  7. Distinct histopathology of acute onset or abrupt exacerbation of hypersensitivity pneumonitis.

    PubMed

    Hariri, Lida P; Mino-Kenudson, Mari; Shea, Barry; Digumarthy, Subba; Onozato, Maristela; Yagi, Yukako; Fraire, Armando E; Matsubara, Osamu; Mark, Eugene J

    2012-05-01

    Hypersensitivity pneumonitis is an inflammatory lung disease that develops in response to exposure to antigen. Cases can be stratified by the duration of exposure and speed of symptom progression into acute, subacute, and chronic hypersensitivity pneumonitis. Although the pathologic features of subacute hypersensitivity pneumonitis are well established and those of chronic hypersensitivity pneumonitis have been reported, little is known about the histopathology of acute hypersensitivity pneumonitis. We evaluated the pathologic features of 5 patients with clinically confirmed hypersensitivity pneumonitis and rapid onset of symptoms and 3 patients with subacute or chronic hypersensitivity pneumonitis with symptom exacerbation. Histopathologic features assessed in each case included those characteristic of subacute hypersensitivity pneumonitis (bronchiolocentric chronic inflammation, histiocytic aggregates, and bronchiolitis obliterans), those associated with acute inflammation (fibrin deposition and neutrophilic infiltrate), and fibrosis. The classic features of hypersensitivity pneumonitis were identified in all 8 cases, with 1 also exhibiting fixed fibrosis confirming underlying chronic hypersensitivity pneumonitis. Fibrin deposition was present in 8 (100%) of 8 cases, and its extent was significant (28% surface area fibrin deposition/total disease area on average). Two had intra-alveolar fibrin so marked that it resembled acute fibrinous and organizing pneumonia. In addition, prominent interstitial neutrophilic infiltrate (≥5 cells/high-power field) was seen in all cases. These features have not been reported as characteristics of subacute or chronic hypersensitivity pneumonitis. Increased fibrin deposition and neutrophilic infiltrate may characterize acute hypersensitivity pneumonitis or abrupt exacerbation of hypersensitivity pneumonitis, and these along with characteristic features of subacute hypersensitivity pneumonitis (granulomatous inflammation and

  8. Radiation-induced lung injury: a hypersensitivity pneumonitis

    SciTech Connect

    Gibson, P.G.; Bryant, D.H.; Morgan, G.W.; Yeates, M.; Fernandez, V.; Penny, R.; Breit, S.N.

    1988-08-15

    Radiation pneumonitis occurs 6 to 12 weeks after thoracic irradiation, and is thought to be due to direct radiation-induced lung injury. Four patients who developed pneumonitis after unilateral thoracic irradiation for carcinoma of the breast were studied with bronchoalveolar lavage, gallium scan of the lung, and respiratory function tests. On the irradiated side of the chest, all four patients showed an increase in total cells recovered from the lavage fluid and a marked increase in the percentage of lymphocytes. When results for the unirradiated lung were compared with results for the irradiated lung, there was a comparable increase in total cells and percentage of lymphocytes. Gallium scans showed increases for both irradiated and unirradiated lungs. Prompt improvement was seen after corticosteroid therapy in all patients. The fact that abnormal findings occur equally in irradiated and unirradiated lung is inconsistent with simple direct radiation-induced injury and suggests an immunologically mediated mechanism such as a hypersensitivity pneumonitis.

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

    PubMed

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

    2010-04-01

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

  10. [Measurement of bird specific antibody in bird-related hypersensitivity pneumonitis].

    PubMed

    Inase, Naohiko; Unoura, Koji; Miyazaki, Yasunari; Yasui, Makito; Yoshizawa, Yasuyuki

    2011-10-01

    Since the avian antigen is one of the important causative antigens in hypersensitivity pneumonitis, measurement of bird-specific antibody should be readily available. We measured IgG and IgA antibodies against pigeons and budgerigars by the ImmunoCap system in bird-related hypersensitivity pneumonitis (BRHP) to evaluate their diagnostic utility. In acute BRHP, antibodies markedly increased and showed high sensitivity and specificity ranging from 75-100% based on the cut-off values determined by ROC analysis. In chronic BRHP, antibody reactivity slightly increased, showing a sensitivity of 27-73% and specificity of 45-100%. Pigeon antibodies evaluated by the ImmunoCap system showed a good correlation with anti-pigeon dropping extract antibodies measured by ELISA. In conclusion, measurement of antibodies against pigeons and budgerigars are helpful for the diagnosis of BRHP. PMID:22117306

  11. Hypersensitivity pneumonitis and related conditions in the work environment.

    PubMed

    Zacharisen, Michael C; Fink, Jordan N

    2011-11-01

    Hypersensitivity pneumonitis can occur from a wide variety of occupational exposures. Although uncommon and difficult to recognize, through a detailed work exposure history, physical examination, radiography, pulmonary function studies, and selected laboratory studies using sera and bronchoalveolar lavage fluid, workers can be identified early to effect avoidance of the antigen and institute pharmacologic therapy, if necessary. A lung biopsy may be necessary to rule out other interstitial lung diseases. Despite the varied organic antigen triggers, the presentation is similar with acute, subacute, or chronic forms. Systemic corticosteroids are the only reliable pharmacologic treatment but do not alter the long-term outcome.

  12. 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.

  13. Metalworking fluid-associated hypersensitivity pneumonitis: a workshop summary.

    PubMed

    Kreiss, K; Cox-Ganser, J

    1997-10-01

    A workshop discussing eight clusters of hypersensitivity pneumonitis in the automotive industry among metalworking fluid-exposed workers concluded that a risk exists for this granulomatous lung disease where water-based fluids are used and unusual microbial contaminants predominate. Strong candidates for microbial etiology are nontuberculous mycobacteria and fungi. Cases of hypersensitivity pneumonitis occur among cases with other work-related respiratory symptoms and chest diseases. Reversibility of disease has occurred in many cases with exposure cessation, allowing return to work to jobs without metalworking fluid exposures or, in some situations, to jobs without the same metalworking fluid exposures. Cases have been recognized with metalworking fluid exposures generally less than 0.5 mg/m3. The workshop participants identified knowledge gaps regarding risk factors, exposure-response relationships, intervention efficacy, and natural history, as well as surveillance needs to define the extent of the problem in this industry. In the absence of answers to these questions, guidance for prevention is necessarily limited.

  14. [A case of hypersensitivity pneumonitis caused by zinc fume].

    PubMed

    Miyazaki, Hiroo; Hirata, Takeo; Shimane, Shoko; Morita, Sumihito; Chihara, Koji; Enomoto, Noriyuki; Suda, Takafumi; Chida, Kingo

    2006-12-01

    A 55-year-old man with a 3-year occupational history of welding was admitted for repeated episodes of fever, cough and dyspnea after inhalation of smoke while welding galvanized steel. A computed tomography (CT) showed diffuse centrilobular nodules, panlobular ground-glass opacity and interlobular septal thickening in both lung fields, and he suffered from hypoxemia (PaO2 = 55.3Torr) while breathing room air. Percentage of lymphocytes in bronchoalveolar lavage fluid increased, and lung biopsy specimens at thoracoscopy revealed lymphocytic alveolitis and organization in air spaces. His symptoms and signs disappeared spontaneously only when he ceased welding. Panlobular ground-glass opacity and interlobular septal thickening improved immediately with oral corticosteroids. Patch tests using metal series gave positive reactions to zinc. We diagnosed this case as hypersensitivity pneumonitis caused by zinc fumes.

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

    PubMed

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

    2009-01-01

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

  16. Combined pulmonary fibrosis and emphysema in hypersensitivity pneumonitis.

    PubMed

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

    2015-12-21

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

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

    PubMed

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

    2009-01-01

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

  18. 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

  19. 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.

  20. 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

  1. 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

  2. Hypersensitivity pneumonitis: a historical, clinical, and radiologic review.

    PubMed

    Hirschmann, Jan V; Pipavath, Sudhakar N J; Godwin, J David

    2009-11-01

    Most cases of hypersensitivity pneumonitis develop only after many years of inhaling allergens, which include microbes, animal or plant proteins, and certain chemicals that form haptens. The initial clinical presentation is either episodes of acute illness with dyspnea and prominent constitutional symptoms, such as fever, or an insidious onset of dyspnea, coughing, and weight loss, sometimes with superimposed acute episodes. The histopathologic process consists of chronic inflammation of the bronchi and peribronchiolar tissue, often with poorly defined granulomas and giant cells in the interstitium or alveoli. Fibrosis and emphysema may develop. The radiologic findings include diffuse ground-glass opacification, centrilobular ground-glass opacities, air trapping, fibrosis, lung cysts, and emphysema. The histologic and radiologic features in some cases may resemble those of usual interstitial pneumonia or nonspecific interstitial pneumonia. The diagnosis usually rests on a variable combination of findings from history, serology, radiography, lung biopsy, and bronchoalveolar lavage, which characteristically reveals a lymphocyte content of more than 30%, often with an increased CD4-to-CD8 ratio of T cells. Treatment includes avoiding the allergen, if possible, and, in severe cases, systemic corticosteroids. The long-term prognosis is usually good, but some patients develop severe respiratory insufficiency, and a few die of the disease.

  3. Stachybotrys chartarum-Induced Hypersensitivity Pneumonitis Is TLR9 Dependent

    PubMed Central

    Bhan, Urvashi; Newstead, Michael J.; Zeng, Xianying; Ballinger, Megan N.; Standiford, Louis R.; Standiford, Theodore J.

    2011-01-01

    Hypersensitivity pneumonitis (HP), an inflammatory lung disease, develops after repeated exposure to inhaled particulate antigen and is characterized by a vigorous T helper type 1-mediated immune response, resulting in the release of IL-12 and interferon (IFN)-γ. These T helper type 1 cytokines may participate in the pathogenesis of HP. Stachybotrys chartarum (SC) is a dimorphic fungus implicated in a number of respiratory illnesses, including HP. Here, we have developed a murine model of SC-induced HP that reproduces pathology observed in human HP and hypothesized that toll receptor-like 9 (TLR9)-mediated dendritic cell responses are required for the generation of granulomatous inflammation induced by inhaled SC. Mice sensitized and challenged with 106 SC spores develop granulomatous inflammation with multinucleate giant cells, accompanied by increased accumulation of neutrophils and CD4+ and CD8+ T cells. SC sensitization and challenge resulted in robust pulmonary expression of tumor necrosis factor-α, IL-12, and IFN-γ. SC-mediated granulomatous inflammation required IFN-γ and was TLR9 dependent, because TLR9−/− mice displayed reduced peribronchial inflammation, decreased accumulation and/or activation of polymorphonuclear (PMN) and CD4+ and CD8+ T cells, and reduced lung expression of type 1 cytokines and chemokines. T-cell production of IFN-γ was IL-12 dependent. Our studies suggest that TLR9 is critical for dendritic cell-mediated development of a type 1 granulomatous inflammation in the lung in response to SC. PMID:21982832

  4. [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

  5. Risk of hypersensitivity pneumonitis and interstitial lung diseases among pigeon breeders.

    PubMed

    Cramer, Christine; Schlünssen, Vivi; Bendstrup, Elisabeth; Stokholm, Zara Ann; Vestergaard, Jesper Medom; Frydenberg, Morten; Kolstad, Henrik Albert

    2016-09-01

    We studied the risk of hypersensitivity pneumonitis and other interstitial lung diseases (ILDs) among pigeon breeders.This is a retrospective follow-up study from 1980 to 2013 of 6920 pigeon breeders identified in the records of the Danish Racing Pigeon Association. They were compared with 276 800 individually matched referents randomly drawn from the Danish population. Hospital based diagnoses of hypersensitivity pneumonitis and other ILDs were identified in the National Patient Registry 1977-2013. Stratified Cox regression analyses estimated the hazard ratios (HR) of hypersensitivity pneumonitis and other ILDs adjusted for occupation, residence and redeemed prescription of medication with ILDs as a possible side-effect. Subjects were censored at death, emigration or a diagnosis of connective tissue disease.The overall incidence rate of ILD was 77.4 per 100 000 person-years among the pigeon breeders and 50.0 among the referents. This difference corresponded to an adjusted HR of 1.56 (95% CI 1.26-1.94). The adjusted HRs of hypersensitivity pneumonitis and other ILDs for pigeon breeders were 14.36 (95% CI 8.10-25.44) and 1.33 (95% CI 1.05-1.69), respectively.This study shows an increased risk of ILD among pigeon breeders compared with the referent population. Protective measures are recommended even though ILD leading to hospital contact remains rare among pigeon breeders.

  6. Hypersensitivity pneumonitis due to inhalation of fungi-contaminated esparto dust in a plaster worker.

    PubMed

    Moreno-Ancillo, A; Padial, M A; López-Serrano, M C; Granado, S

    1997-01-01

    Hypersensitivity pneumonitis or extrinsic allergic alveolitis can be defined as a lung disease caused by a wide group of antigens that reach the lung by inhalation of organic and/or inorganic dust of various sources. The esparto (Stipa Tenacissima and Ligeum Spartum) is an herbaceous of the grass family used in the production of ropes, canvas, sandals, mats, baskets, and so forth. It is also used in the construction industry for the production of paper paste. Inhalation of esparto dust has been reported as cause of hypersensitivity pneumonitis. The existence of precipitating antibodies against esparto extract has been proved. During the esparto fiber manufacturing process, esparto grass can be contaminated by moulds and thermophilic actinomycetes, which have been described as the causing antigens of hypersensitivity pneumonitis in plaster workers. We present a case of occupational hypersensitivity pneumonitis in a plaster worker. Clinical findings, precipitating antibodies, and evolution, after having removed him from his work, confirmed the diagnosis. In our case, Aspergillus species contaminating esparto are probably the antigens that caused the disease.

  7. Familial Summer-type Hypersensitivity Pneumonitis: A Review of 25 Families and 50 Cases in Japan.

    PubMed

    Asai, Nobuhiro; Kaneko, Norihiro; Ohkuni, Yoshihiro; Aoshima, Masahiro; Kawamura, Yasutaka

    2016-01-01

    Summer-type hypersensitivity pneumonitis (SHP) is the most common form of pneumonitis in Japan; it accounts for 74% of all cases. It has been reported that 19.5-23.8% of SHP cases occur in families who live in the same house. We present our SHP cases and review 50 familial cases in 23 families that were reported in Japan (including our own) and 48 cases that were previously described in 22 articles published between January 1982 and October 2011. To the best of the authors' knowledge, this is the first review article in English to document the familial occurrence of SHP in Japan.

  8. 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

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

    PubMed

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

    1993-10-01

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

  10. Hypersensitivity pneumonitis due to metalworking fluids: how to find the antigens.

    PubMed

    Merget, R; Sander, I; van Kampen, V; Raulf-Heimsoth, M; Rabente, T; Kolk, A; Brüning, Th

    2013-01-01

    Most surveys of outbreaks of hypersensitivity pneumonitis (HP) in subjects with occupational exposure to water-based metalworking fluids (MWFs) were unable to detect a clear link between symptoms and the precise causative agents. We studied the case of a male 41-year-old industrial knife grinder with exposure to water-based MWFs since 12 years. The diagnosis of HP was made by typical work-related symptoms, the demonstration of high lymphocyte numbers in bronchoalveolar lavage and elevated IgG antibody concentrations to various molds in the patient's serum, and complete recovery after early exposure cessation. Whereas an environmental survey showed only low numbers of mold contamination in one sump sample, high antigenic activity was demonstrated in the same sample by antigen-specific IgG inhibition tests. We conclude that the detection of antigenic molds in water-based MWFs by culture methods may be limited. The link between occupational exposure to specific molds in MWFs and hypersensitivity pneumonitis can be established by the demonstration of antigenic activity by antigen-specific IgG inhibition tests. PMID:23835995

  11. 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

  12. 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.

  13. [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.

  14. Immuno-reactive proteins from Mycobacterium immunogenum useful for serodiagnosis of metalworking fluid hypersensitivity pneumonitis.

    PubMed

    Roussel, Sandrine; Rognon, Bénédicte; Barrera, Coralie; Reboux, Gabriel; Salamin, Karine; Grenouillet, Frédéric; Thaon, Isabelle; Dalphin, Jean-Charles; Tillie-Leblond, Isabelle; Quadroni, Manfredo; Monod, Michel; Millon, Laurence

    2011-02-01

    Metalworking fluid-associated hypersensitivity pneumonitis (MWF-HP) is a pulmonary disease caused by inhaling microorganisms present in the metalworking fluids used in the industrial sector. Mycobacterium immunogenum is the main etiological agent. Among the clinical, radiological and biological tools used for diagnosis, serological tests are important. The aim of this study was to identify immunogenic proteins in M. immunogenum and to use recombinant antigens for serological diagnosis of MWF-HP. Immunogenic proteins were detected by two-dimensional Western blot and candidate proteins were identified by mass spectrometry. Recombinant antigens were expressed in Escherichia coli and tested by enzyme-linked immunosorbent assay (ELISA) with the sera of 14 subjects with MWF-HP and 12 asymptomatic controls exposed to M. immunogenum. From the 350 spots visualized by two-dimensional gel electrophoresis with M. immunogenum extract, 6 immunogenic proteins were selected to be expressed as recombinant antigens. Acyl-CoA dehydrogenase antigen allowed for the best discrimination of MWF-HP cases against controls with an area under the receiver operating characteristics (ROC) curve of 0.930 (95% CI=0.820-1), a sensitivity of 100% and a specificity of 83% for the optimum threshold. Other recombinant antigens correspond to acyl-CoA dehydrogenase FadE, cytosol aminopeptidase, dihydrolipoyl dehydrogenase, serine hydroxymethyltransferase and superoxide dismutase. This is the first time that recombinant antigens have been used for the serodiagnosis of hypersensitivity pneumonitis. The availability of recombinant antigens makes it possible to develop standardized serological tests which in turn could simplify diagnosis, thus making it less invasive. PMID:20850379

  15. Hypersensitivity Pneumonitis-like Granulomatous Lung Disease with Nontuberculous Mycobacteria from Exposure to Hot Water Aerosols

    PubMed Central

    Sood, Akshay; Sreedhar, Rajgopal; Kulkarni, Pradeep; Nawoor, Abdur Ray

    2007-01-01

    Objective Human activities associated with aerosol-generating hot water sources are increasingly popular. Recently, a hypersensitivity pneumonitis (HP)-like granulomatous lung disease, with non-tuberculous mycobacteria from exposure to hot water aerosols from hot tubs/spas, showers, and indoor swimming pools, has been described in immunocompetent individuals (also called “hot tub lung”). Our objective in this study was to examine four additional cases of hot tub lung and compare these cases with others reported in the English print literature on this disease. Data sources and extraction We retrospectively reviewed all cases (n = 4) of presumptively diagnosed hot tub lung in immunocompetent individuals at the various physician practices in Springfield, Illinois, during 2001–2005. In addition, we searched MEDLINE for cases of hot tub lung described in the literature. Data synthesis We summarized the clinical presentation and investigations of four presumptive cases and reviewed previously reported cases of hot tub lung. Conclusions There is a debate in the literature whether hot tub lung is an HP or a direct infection of the lung by nontuberculous mycobacteria. Primary prevention of this disease relies on ventilation and good use practices. Secondary prevention of this disease requires education of both the general public and clinicians to allow for the early diagnosis of this disease. PMID:17384775

  16. 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

  17. 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.

  18. Seasonal variation of serum KL-6 concentrations is greater in patients with hypersensitivity pneumonitis

    PubMed Central

    2014-01-01

    Background Serum KL-6 is a useful biomarker for the diagnosis of interstitial lung diseases (ILD). However, KL-6 has not been used to discriminate different types of ILD. Serum KL-6 concentrations can vary depending on antigen exposure levels in patients with hypersensitivity pneumonitis (HP); however, seasonal changes in serum KL-6 concentrations in ILD have not been determined. We hypothesized that seasonal variation of serum KL-6 is greater in HP than for the other ILD. The aim of this study was to determine seasonal variation of serum KL-6 concentrations in various ILD. Methods Serum KL-6 concentrations in the summer season from June 1 to September 30 and the winter season from November 1 to February 28 were retrospectively analyzed in patients with idiopathic pulmonary fibrosis (IPF, n = 16), non-specific interstitial pneumonia (NSIP, n = 16), collagen vascular disease-associated interstitial pneumonia (CVD-IP, n = 33), house-related HP (House-HP, n = 9), bird-related HP (Bird-HP, n = 9), and combined pulmonary fibrosis and emphysema (CPFE, n = 13). Results Bird-HP and House-HP showed greater seasonal serum KL-6 variation than the other ILD. Serum KL-6 concentrations in Bird-HP were significantly increased in the winter and KL-6 concentrations in House-HP were significantly increased in the summer. Serum KL-6 variation was significantly greater in acute HP than chronic HP. Receiver operating characteristic curve analysis revealed that greater seasonal variation in serum KL-6 concentrations is diagnostic for Bird-HP. Conclusion HP should be considered in ILD with greater seasonal changes in serum KL-6 concentrations. PMID:25098177

  19. Successful treatment of hypersensitivity pneumonitis caused by Grifola frondosa (Maitake) mushroom using a HFA-BDP extra-fine aerosol.

    PubMed

    Tanaka, Hiroshi; Tsunematsu, Kazunori; Nakamura, Naohito; Suzuki, Kazuhiko; Tanaka, Nobuyuki; Takeya, Isao; Saikai, Toyohiro; Abe, Shosaku

    2004-08-01

    We successfully treated a patient with occupational hypersensitivity pneumonitis (HP) caused by Grifola frondosa (Maitake) mushroom spore with an extra-fine aerosol corticosteroid; beclomethasone dipropionate (BDP) dissolved in hydrofluoroalkane-134a (HFA). A 49-year-old woman developed respiratory symptoms 3 months after beginning work on a mushroom farm. She was diagnosed as HP based on radiological and serological findings. Oral prednisolone therapy improved her HP and she returned to the same farm. Her HP relapsed after 5 months, and daily 400 microg of HFA-BDP was administered with gradual improvement. An extra-fine particle inhaled corticosteroid might reach appropriate alveoli to be effective therapy for mild HP.

  20. Hypersensitivity pneumonitis caused by esparto dust in a young plaster worker: a case report and review of the literature.

    PubMed

    Flandes, Javier; Heili, Sarah; Gómez Seco, Julio; Sabillón, Oscar; Fernández, Itziar; Ortega, Angel

    2004-01-01

    We report a case of a 25-year-old, white, male plaster worker who started developing fever, severe dyspnea and cough during the manipulation of esparto fibers. The functional lung study showed restrictive lung disease and decreased single-breath carbon monoxide transfer lung capacity. High-resolution computed tomography revealed a diffuse 'ground-glass' pattern. The histopathological findings were interstitial inflammation with a marked predominance of lymphocytes and microgranulomas. Bronchoalveolar lavage showed a significant predominance of lymphocytes, with an increase in the level of CD8. Serum precipitins against fungal antigens confirmed that Aspergillus fumigatus was the cause of the patient's hypersensitivity pneumonitis.

  1. [A patient with acute hypersensitivity pneumonitis with a diagnosis of air-conditioner lung, who responded to therapy].

    PubMed

    Ishikawa, Rie; Kamiya, Hiroyuki; Ikushima, Souichiro; Oristu, Masaru; Takemura, Tamiko

    2010-02-01

    The patient was a 48-year-old woman and current smoker. In May 2007, she moved to a new residence. In the middle of the following month, she developed acute respiratory distress and a fever (38 degrees C) after running her air conditioner continuously throughout the night. The chest X-ray film showed diffuse infiltrative shadows in the middle and lower lung fields. After hospital admission, her oxygenation improved without treatment and the infiltrates improved over the clinical course. As a consequence, we suspected hypersensitivity pneumonitis. The bronchoalveolar lavage showed predominant lymphocytes of 72.6%, with a low CD 4/8 ratio of 0.2. Transbronchial lung biopsy findings corresponded to acute hypersensitivity pneumonitis. The results of the environmental challenge test were positive only when her air conditioner was on, resulting, in a diagnosis of air-conditioner lung. Several microorganisms were detected in an environmental sample, but 20 kinds of serum precipitating antibodies were negative on a thorough screening, so no responsible antigen could be identified. The patient's symptoms did not recur after her air conditioner was replaced. PMID:20184245

  2. Measurement of IgG antibody and airborne antigen to control an industrial outbreak of hypersensitivity pneumonitis

    SciTech Connect

    Reed, C.E.; Swanson, M.C.; Lopez, M.; Ford, A.M.; Major, J.; Witmer, W.B.; Valdes, T.B.

    1983-03-01

    An outbreak of hypersensitivity pneumonitis in a textile plant was attributed on epidemiological grounds to a chilled water air-conditioning system where a slime was growing in the chilled water sump and on demister vanes. All of the patients and about 80% of their asymptomatic co-workers had strongly positive precipitin tests to extracts of the slime. An adaptation of a radioiodinated staphylococcal protein A solid-phase radioimmunoassay was applied to monitor antigen and specific antibody. To control the outbreak, a variety of cleaning and water treatment measures were taken between 1977 and 1979 to reduce the amount of antigen in the water and in the air. The amount of slime in the water was greatly reduced though the antigen content per gram of slime did not change. Airborne antigen in the affected work areas decreased progressively.

  3. 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.

  4. INCIDENCE AND CORRELATES OF RADIATION PNEUMONITIS IN PEDIATRIC PATIENTS WITH PARTIAL LUNG IRRADIATION

    PubMed Central

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

    2012-01-01

    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 V10–V25, 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 (χ2 test, p = 0.027) and V24 (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 V24 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. PMID:20056346

  5. [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

  6. TLR9-Dependent IL-23/IL-17 is Required for the Generation of Stachybotrys chartarum-induced Hypersensitivity Pneumonitis

    PubMed Central

    Bhan, Urvashi; Newstead, Michael J.; Zeng, Xianying; Podsaid, Amy; Goswami, Moloy; Ballinger, Megan N.; Kunkel, Steven L.; Standiford, Theodore J.

    2012-01-01

    Hypersensitivity pneumonitis (HP) is an inflammatory lung disease that develops following repeated exposure to inhaled particulate antigen. Stachybotrys chartarum (SC) is a dimorphic fungus that has been implicated in a number of respiratory illnesses, including HP (1). In this study we have developed a murine model of SC- induced HP that reproduces pathology observed in human HP and hypothesized that TLR9–mediated IL-23/IL-17 responses are required for the generation of granulomatous inflammation induced by inhaled SC. Mice that undergo i.p. sensitization and i.t. challenge with 106 SC spores developed granulomatous inflammation with multinucleate giant cells, accompanied by increased accumulation of T cells. SC sensitization and challenge resulted in robust pulmonary expression of IL-17 and IL-23. SC-mediated granulomatous inflammation required intact IL-23/IL-17 responses and required TLR9, as TLR9−/− mice displayed reduced IL-17 and IL-23 expression in whole lung associated with decreased accumulation of IL-17 expressing CD4+ and γδ T cells. As compared to SC-sensitized dendritic cells (DC) isolated from WT mice, DC isolated from TLR9−/− mice had a reduced ability to produce IL-23 in responses to SC. Moreover, shRNA knockdown of IL-23 in DC abolished IL-17 production from splenocytes in response to antigen challenge. Finally, the i.t. reconstitution of IL-23 in TLR9−/− mice recapitulated the immunopathology observed in WT mice. In conclusion, our studies suggest that TLR9 is critical for development of Th17-mediated granulomatous inflammation in the lung in response to SC. PMID:23180821

  7. [A case of isocyanate-induced hypersensitivity pneumonitis and a compression-air mask thought to be effective in its prevention].

    PubMed

    Idezuka, J; Ikarashi, H; Nozawa, S; Maruyama, M; Sasagawa, M; Suzuki, E

    1991-07-01

    A 41-year-old paint sprayer, who had worked with polyurethane paint since the spring of 1989, developed exertional dyspnea and dry cough and entered hospital on December 4, 1989. Plain chest X-ray film and a computed tomogram of the lung revealed diffuse micronodular shadows in both lower lung fields. DLco was shown to be significantly decreased in a pulmonary function test. A sample of bronchoalveolar lavage fluid showed increased T lymphocytes and a decreased CD4/8 ratio. A lung biopsy specimen revealed alveolitis, but neither Masson body nor granulomas were seen. Serum antibody specific to TDI-HSA was detected, and an environmental provocation test was positive. From these results, the patient was diagnosed as having isocyanate-induced hypersensitivity pneumonitis. We advised him to wear a compression-air mask when he worked, because he did not want to quit his job. Respiratory symptoms have not been seen since then, but careful observation was thought to be necessary. The involvement of type III humoral and type IV cellular immunity was suspected in this case.

  8. Genetic susceptibility to multicase hypersensitivity pneumonitis is associated with the TNF-238 GG genotype of the promoter region and HLA-DRB1*04 bearing HLA haplotypes.

    PubMed

    Falfán-Valencia, Ramcés; Camarena, Angel; Pineda, César Landa; Montaño, Martha; Juárez, Armida; Buendía-Roldán, Ivette; Pérez-Rubio, Gloria; Reséndiz-Hernández, Juan Manuel; Páramo, Ignacio; Vega, Anita; Granados, Julio; Zúñiga, Joaquín; Selman, Moisés

    2014-01-01

    Hypersensitivity Pneumonitis (HP) is a lung inflammatory disorder caused by inhalation of organic particles by a susceptible host. Since only a small proportion of individuals exposed to HP-related antigens develop the disease, a genetic predisposition is largely suspected. However, studies regarding genetic susceptibility in this disease are scanty. We have previously found evidence supporting increased risk associated to the major histocompatibility complex (MHC) in sporadic HP. In the present study, we conducted a family-based research that includes nine multicase families with at least two related HP patients (RHP). We evaluated 19 RHP individuals, 25 additional healthy first-degree relatives (REA) and 246 healthy unrelated individuals (HUI). HLA class II typing (DRB1/3/4/5, DQA1, DQB1, DPA1, DPB1, DMA and DMB), and -863, -308 and -238 polymorphisms in the promoter region of TNF-α were performed by PCR based methods. We identified an increased frequency of HLA-DRB1*04:07, DRB1*04:05, DRB1*11:01 and DRB1*13:01 alleles in RHP individuals compared to healthy controls (p < 0.05). A significant higher frequency of DRB1*04:07-DQB1*03:02, DRB1*04:05-DQB1*03:02, and DRB1*04:03-DQB1*03:02 haplotypes was also detected in the group of patients. Likewise, TNF-238 GG genotype was more frequent in the RHP group as compared to REA (p = 0.01, OR = 7.2). Finally, the combination of HLA-DRB1*04 alleles and TNF-238 GG was significantly increased in the RHP group (p = 0.01, OR = 6.93). These findings indicate that genes located within the MHC region confer susceptibility to familial HP in Mexicans. PMID:24291122

  9. Correlation between pneumonitis risk in radiation oncology and lung density measured with X-ray computed tomography

    PubMed Central

    Balosso, Jacques

    2016-01-01

    Background The risk of toxicity with radiation oncology for lung cancer limits the maximal radiation dose that can be delivered to thoracic tumors. This study aims at investigating the correlation between normal tissue complication probability (NTCP) and physical lung density by analyzing the computed tomography (CT) scan imaging used for radiotherapy dose planning. Methods Data from CT of lung cancer patients (n=10), treated with three dimensional radiotherapy, were selected for this study. The dose was calculated using analytical anisotropic algorithm (AAA). Dose volume histograms (DVH) for healthy lung (lung excluding targets) were calculated. The NTCP for lung radiation induced pneumonitis was computed using initial radiobiological parameters from Lyman-Kutcher and Burman (LKB) model and readjusted parameters for AAA, with α/β=3. The correlation coefficient “rho” was calculated using Spearman’s rank test. The bootstrap method was used to estimate the 95% confidence interval (95% CI). Wilcoxon paired test was used to calculate P values. Results Bootstrapping simulation revealed significant difference between NTCP computed with the initial radiobiological parameters and that computed with the parameters readjusted for AAA (P=0.03). The results of simulations based on 1,000 replications showed no correlation for NTCP with density, with “rho” <0.3. Conclusions For a given set of patients, we assessed the correlation between NTCP and lung density using bootstrap analysis. The lack of correlation could result either from a very accurate dose calculation, by AAA, whatever the lung density yielding a NTCP result only dependant of the dose and not any more of the density; or to the very limited range of natural variation of relative electronic density (0.15 to 0.20) observed in this small series of patients. Another important parameter is the bootstrap simulation with 1,000 random samplings may have underestimated the correlation, since the initial data (n

  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. Cross-allergenicity in the legume botanical family in children with food hypersensitivity. II. Laboratory correlates.

    PubMed

    Bernhisel-Broadbent, J; Taylor, S; Sampson, H A

    1989-11-01

    Only two of 41 legume-allergic patients diagnosed by double-blind, placebo-controlled oral food challenge or "convincing history" of anaphylaxis had an IgE-mediated hypersensitivity reaction to more than one member of the legume family. However, extensive immunologic cross-reactivity was demonstrated among legume antigens on Immunoblot and Immunodot-blot analyses and prick skin tests. The proteins of six legumes (peanut, soybean, lima bean, pea, garbanzo bean, and green beans) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, and probed with sera from six legume-allergic patients. Multiple IgE-binding bands were identified in each legume lane by the sera from each of these legume-allergic patients. In vitro cross-reactivity did not correlate with clinical hypersensitivity. All the legumes studied (except green bean) had a prominent band at 20 kd. Numerous proteins and protein subunits can be identified in each of the legumes (16 peanut, 21 soybean, 23 lima bean, 25 pea, 22 garbanzo bean, and 11 green bean protein bands) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it appears that legume-allergic patients' sera may recognize multiple similar fractions from each legume. A second in vitro test was performed in which the six legume extracts were bound directly onto nitrocellulose paper. These "legume" Immunodot blots were probed for specific IgE-binding activity with sera from 62 patients with positive legume prick skin tests. The legume Immunodot blots again demonstrated extensive clinically irrelevant cross-reactivity. However, this test may prove useful as a simple technique for screening food-specific IgE with minimal quantities of sera.

  12. 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

  13. Immune defense against pneumonic plague

    PubMed Central

    Smiley, Stephen T.

    2009-01-01

    Summary Yersinia pestis is one of the world's most virulent human pathogens. Inhalation of this Gram-negative bacterium causes pneumonic plague, a rapidly progressing and usually fatal disease. Extensively antibiotic-resistant strains of Y. pestis exist and have significant potential for exploitation as agents of terrorism and biowarfare. Subunit vaccines comprised of the Y. pestis F1 and LcrV proteins are well-tolerated and immunogenic in humans but cannot be tested for efficacy, because pneumonic plague outbreaks are uncommon and intentional infection of humans is unethical. In animal models, F1/LcrV-based vaccines protect mice and cynomolgus macaques but have failed, thus far, to adequately protect African green monkeys. We lack an explanation for this inconsistent efficacy. We also lack reliable correlate assays for protective immunity. These deficiencies are hampering efforts to improve vaccine efficacy. Here, I review the immunology of pneumonic plague, focusing on evidence that humoral and cellular defense mechanisms collaborate to defend against pulmonary Y. pestis infection. PMID:18837787

  14. Hypersensitive Glutamate Signaling Correlates with the Development of Late-Onset Behavioral Morbidity in Diffuse Brain-Injured Circuitry

    PubMed Central

    Thomas, Theresa Currier; Hinzman, Jason M.; Gerhardt, Greg A.

    2012-01-01

    Abstract In diffuse brain-injured rats, robust sensory sensitivity to manual whisker stimulation develops over 1 month post-injury, comparable to agitation expressed by brain-injured individuals with overstimulation. In the rat, whisker somatosensation relies on thalamocortical glutamatergic relays between the ventral posterior medial (VPM) thalamus and barrel fields of somatosensory cortex (S1BF). Using novel glutamate-selective microelectrode arrays coupled to amperometry, we test the hypothesis that disrupted glutamatergic neurotransmission underlies the whisker sensory sensitivity associated with diffuse brain injury. We report hypersensitive glutamate neurotransmission that parallels and correlates with the development of post-traumatic sensory sensitivity. Hypersensitivity is demonstrated by significant 110% increases in VPM extracellular glutamate levels, and 100% increase in potassium-evoked glutamate release in the VPM and S1BF, with no change in glutamate clearance. Further, evoked glutamate release showed 50% greater sensitivity to a calcium channel antagonist in brain-injured over uninjured VPM. In conjunction with no changes in glutamate transporter gene expression and exogenous glutamate clearance efficiency, these data support a presynaptic origin for enduring post-traumatic circuit alterations. In the anatomically-distinct whisker circuit, the injury-induced functional alterations correlate with the development of late-onset behavioral morbidity. Effective therapies to modulate presynaptic glutamate function in diffuse-injured circuits may translate into improvements in essential brain function and behavioral performance in other brain-injured circuits in rodents and in humans. PMID:21939393

  15. 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

  16. Postsplenectomy type-1 hypersensitivity response: a correlation between IL-4 and IgE serum levels.

    PubMed

    Miniello, Stefano; Cristallo, Graziana; Testini, Mario; Balzanelli, Mario Giosuè; Marzaioli, Rinaldo; Venezia, Pietro; Lissidini, Germana; Petrozza, Dino; Nacchiero, Michele

    2008-01-01

    Authors demonstrated the presence of allergic manifestations in splenectomized patients following traumatic rupture of this organ. In particular, allergic diathesis, as supported by serum IgE increase, was exclusively found in patients with preserved T helper (h)-2 lymphocyte function. Th-2 function was monitored by measuring serum levels of interleukin (IL)-4, a cytokine involved in IgE synthesis. On the opposite, in splenectomized individuals with a reduced Th-2 function as supported by lower IL-4 serum levels, no IgE increase and allergic manifestations were detectable. On these grounds, authors hypothesize that allergic manifestations may be correlated to splenectomy since its exeresis may favor the persistence of antigens in the blood. Consequentially, in patients with a preserved Th-2 function, antigenic overload may lead to IgE increase and allergy onset.

  17. Hypersensitivity to P. officinalis pollen: correlation of IgE with skin testing methods.

    PubMed

    Cvitanović, S; Grbić, D; Zekan, L; Boban, M; Vrdoljak, E; Parpura, V; Petrović, S; Marusić, M

    1989-01-01

    Fifty pollinosis patients, who have reported contact with P. officinalis, were tested for skin sensitivity with P. officinalis pollen extract. Intracutaneous testing and the skin prick method were employed and their sensitivity verified with regard to serum concentrations of specific IgE antibodies determined with the RAST method. Two criteria of the skin prick method evaluation were employed. The intracutaneous method correlated best with RAST. In contrast to intracutaneous testing, the skin prick method did not produce any false-positive results; however, due to a few false-negative cases observed, it appeared that in borderline-negative cases the skin prick method would require determination of serum IgE antibodies to reach a clear-cut diagnosis.

  18. 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

  19. Dentine hypersensitivity.

    PubMed

    West, Nicola; Seong, Joon; Davies, Maria

    2014-01-01

    Dentine hypersensitivity is a common oral pain condition affecting many individuals. The aetiology is multifactorial; however, over recent years the importance of erosion has become more evident. For dentine hypersensitivity to occur, the lesion must first be localised on the tooth surface and then initiated to exposed dentine tubules which are patent to the pulp. The short, sharp pain symptom is thought to be derived from the hydrodynamic pain theory and, although transient, is arresting, affecting quality of life. This episodic pain condition is likely to become a more frequent dental complaint in the future due to the increase in longevity of the dentition and the rise in tooth wear, particularly amongst young adults. Many efficacious treatment regimens are now available, in particular a number of over-the-counter home use products. The basic principles of treatment are altering fluid flow in the dentinal tubules with tubule occlusion or modifying or chemically blocking the pulpal nerve. PMID:24993261

  20. [Dentinal hypersensitivity].

    PubMed

    Steinkeller-Dekel, M; Smidt, A; Pilo, R

    2010-01-01

    Dentinal hypersensitivity is defined as short and transient painful response of exposed dentin, usually cervical, to different stimuli, such as thermal, mechanical osmotic or chemical. The etiology of dentinal hypersensitivity is open tubules (because of enamel loss or gingival recession), allowing painful stimulus to reach the pulp. The hydrodynamic theory explains the mechanism through which pain is aroused. When treating dentinal hypersensitivity, dentists always have to rule out other pathologies, such as carries, leakage, postoperative sensitivity, cracked tooth etc., and only then assess pain intensity and treat the tooth. Treatment always starts with prevention of both stimulus and exposure of dentin, and reducing predisposing factors. The treatment options include OTC products, such as fluoride and/or potassium enriched mouth washes and dentifrices, or in-office treatments, such as high content fluoride varnishes and gels, potassium oxalate chelating agents, Glutaraldehyde containing tissue fixating agents, bonding materials, low viscosity glass ionomers and even non-conservative treatments such as root canal therapy or mucogingival surgical interventions.

  1. [Dentinal hypersensitivity].

    PubMed

    Steinkeller-Dekel, M; Smidt, A; Pilo, R

    2010-01-01

    Dentinal hypersensitivity is defined as short and transient painful response of exposed dentin, usually cervical, to different stimuli, such as thermal, mechanical osmotic or chemical. The etiology of dentinal hypersensitivity is open tubules (because of enamel loss or gingival recession), allowing painful stimulus to reach the pulp. The hydrodynamic theory explains the mechanism through which pain is aroused. When treating dentinal hypersensitivity, dentists always have to rule out other pathologies, such as carries, leakage, postoperative sensitivity, cracked tooth etc., and only then assess pain intensity and treat the tooth. Treatment always starts with prevention of both stimulus and exposure of dentin, and reducing predisposing factors. The treatment options include OTC products, such as fluoride and/or potassium enriched mouth washes and dentifrices, or in-office treatments, such as high content fluoride varnishes and gels, potassium oxalate chelating agents, Glutaraldehyde containing tissue fixating agents, bonding materials, low viscosity glass ionomers and even non-conservative treatments such as root canal therapy or mucogingival surgical interventions. PMID:20597258

  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. Acute Hepatitis and Pneumonitis Caused by Disseminated Bacillus Calmette-Guérin Infection

    PubMed Central

    Shehadeh, Ihab; Abu Atta, Osama

    2016-01-01

    Intravesical instillation of Bacillus Calmette-Guérin (BCG) is the treatment of choice for superficial bladder carcinoma. We report a case of disseminated BCG infection in an early stage bladder cancer patient that initially presented with hepatitis followed by pneumonitis and sepsis. A complete clinical response was achieved in 14 days with anti-mycobacterial therapy and prednisolone. Disseminated BCG is a rare treatment complication and is likely a combination of direct infection and hypersensitivity. PMID:26958569

  4. 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.

  5. Chromosomal position effects in chicken lysozyme gene transgenic mice are correlated with suppression of DNase I hypersensitive site formation.

    PubMed Central

    Huber, M C; Bosch, F X; Sippel, A E; Bonifer, C

    1994-01-01

    The complete chicken lysozyme gene locus is expressed copy number dependently and at a high level in macrophages of transgenic mice. Gene expression independent of genomic position can only be achieved by the concerted action of all cis regulatory elements located on the lysozyme gene domain. Position independency of expression is lost if one essential cis regulatory region is deleted. Here we compared the DNase I hypersensitive site (DHS) pattern formed on the chromatin of position independently and position dependently expressed transgenes in order to assess the influence of deletions within the gene domain on active chromatin formation. We demonstrate, that in position independently expressed transgene all DHSs are formed with the authentic relative frequency on all genes. This is not the case for position dependently expressed transgenes. Our results show that the formation of a DHS during cellular differentiation does not occur autonomously. In case essential regulatory elements of the chicken lysozyme gene domain are lacking, the efficiency of DHS formation on remaining cis regulatory elements during myeloid differentiation is reduced and influenced by the chromosomal position. Hence, no individual regulatory element on the lysozyme domain is capable of organizing the chromatin structure of the whole locus in a dominant fashion. Images PMID:7937145

  6. 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. PMID:27630988

  7. Influenza SIRS with Minimal Pneumonitis.

    PubMed

    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. PMID:27630988

  8. Avocado hypersensitivity.

    PubMed

    Blanco, C; Carrillo, T; Castillo, R; Quiralte, J; Cuevas, M

    1994-07-01

    The avocado (Av) is a fruit that belongs to the Lauraceae family. We report 17 patients with immediate hypersensitivity to avocado. Clinical manifestations in relation to avocado ingestion were as follows: systemic anaphylaxis in seven patients, angioedema/urticaria in six, vomiting in two, bronchial asthma in one, and rhinoconjunctivitis in one. Skin prick test (SPT) with fresh avocado was positive in all patients with the Strong avocado variety (SAv) and in 14 patients with the Hass avocado variety (HAv). Our patient-associated sensitizations were as follows: 10 to latex, eight to chestnut, eight to banana, four to kiwi, and four to walnut. Avocado-sensitized patients with latex allergy were typically middle-aged women, professionally exposed to latex, who also exhibited frequent associated sensitizations to chestnut, banana, and other fruits. Specific IgE against avocado was demonstrated in 11 of our patients, by both commercial CAP and RAST with avocado extract coupled to nitrocellulose disks. Despite its lower protein content, SAv seems to be more allergenic than HAv, both in vivo and in vitro. On incubating a pool of sera from our patients with avocado, latex, chestnut, and banana extracts, a progressive RAST inhibition was obtained, with SAv- and chestnut-marked disks. This suggests the existence of common antigenic determinants among these allergens.

  9. 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.

  10. Fatal measles pneumonitis during Hodgkin's lymphoma.

    PubMed

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

    2013-10-08

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

  11. Rheumatoid arthritis and cryptogenic organising pneumonitis.

    PubMed

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

    1991-05-01

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

  12. Aspiration syndromes: aspiration pneumonia and pneumonitis.

    PubMed

    Marik, Paul E

    2010-02-01

    Aspiration pneumonia and pneumonitis are common clinical syndromes that occur in hospitalized patients. Aspiration pneumonia occurs in patients with dysphagia and usually presents as a community-acquired pneumonia with a focal infiltrate in a dependent bronchopulmonary segment. Patients with aspiration pneumonia require treatment with broad-spectrum antibiotics and management of the underlying dysphagia. Aspiration pneumonitis follows the aspiration of gastric contents, usually in patients with a marked decreased level of consciousness. Treatment of aspiration pneumonitis is essentially supportive; however, corticosteroids and other immunomodulating agents may have a role in these patients.

  13. [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

  14. Treatment of dentin hypersensitivity.

    PubMed

    Trushkowsky, Richard D; Oquendo, Anabella

    2011-07-01

    Dentinal hypersensitivity is exemplified by brief, sharp, well-localized pain in response to thermal, evaporative, tactile, osmotic, or chemical stimuli that cannot be ascribed to any other form of dental defect or pathology. Pulpal pain is usually more prolonged, dull, aching, and poorly localized and lasts longer than the applied stimulus. Up to 30% of adults have dentinal hypersensitivity at some time. Current techniques for treatment may be only transient in nature and results are not always predictable. Two methods of treatment of dentin hypersensitivity are tubular occlusion and blockage of nerve activity. A differential diagnosis needs to be accomplished before any treatment. PMID:21726693

  15. Platinum hypersensitivity and desensitization.

    PubMed

    Miyamoto, Shingo; Okada, Rika; Ando, Kazumichi

    2015-09-01

    Platinum agents are drugs used for various types of cancer. With increased frequency of administration of platinum agents, hypersensitivity reactions appear more frequently, occurring in over 25% of cases from the seventh cycle or second line onward. It then becomes difficult to conduct treatment using these agents. Various approaches have been investigated to address hypersensitivity reactions to platinum agents. Desensitization, which gradually increases the concentration of the anticancer drug considered to be the antigen until the target dosage, has been reported as being particularly effective, with a success rate of 80-100%. The aims of this paper are to present the current findings regarding hypersensitivity reactions to platinum agents and to discuss attempts of using desensitization against hypersensitivity reactions worldwide.

  16. 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).

  17. Carmine hypersensitivity masquerading as azithromycin hypersensitivity.

    PubMed

    Greenhawt, Matthew; McMorris, Marc; Baldwin, James

    2009-01-01

    Macrolide hypersensitivity is a rarely reported event. However, carmine dye has become increasingly important as a provocative agent. We present a case of a woman with documented carmine hypersensitivity, who reported anaphylaxis 90 minutes after ingestion of a generic azithromycin. Our investigations revealed that this was an allergy to the carmine dye in the tablet's coating rather than to the antibiotic. Seven extracts were prepared including carmine dye, crushed dried female cochineal insects, crushed tablets of Zithromax (Pfizer Inc.) and generic azithromycin (Teva Pharmaceuticals), and the crushed colored coatings from both tablets. These were suspended in preservative-free normal saline, and then applied as a skin-prick test and read at 30 minutes. The skin-prick skin test results were 4+ to histamine and carmine dye, but negative to cochineal insect extract, Pfizer crushed tablets, and negative control. The patient was 1+ to the Teva crushed tablet, but was 4+ to the Teva brand coating and negative to the Pfizer brand coating, which did not contain carmine. The patient subsequently ingested Pfizer Zithromax without any sequelae. To our knowledge, this is the first reported case of carmine anaphylaxis attributed to carmine-containing medication. Careful history and skin-prick testing to the appropriate agents allowed elucidation of the subtlety of the true offending agent without unnecessary avoidance of the medication class. Patients with a carmine hypersensitivity should actively check with their pharmacy or prescribing physician to verify their medications are free of this offending agent. PMID:19331724

  18. Bubonic and pneumonic plague - Uganda, 2006.

    PubMed

    2009-07-24

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

  19. Vaccination against bubonic and pneumonic plague.

    PubMed

    Titball, R W; Williamson, E D

    2001-07-20

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

  20. 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

  1. Hypersensitivity of Arabidopsis TAXIMIN1 overexpression lines to light stress is correlated with decreased sinapoyl malate abundance and countered by the antibiotic cefotaxime

    PubMed Central

    Colling, Janine; Pollier, Jacob; Bossche, Robin Vanden; Makunga, Nokwanda Pearl; Pauwels, Laurens; Goossens, Alain

    2016-01-01

    ABSTRACT Peptide signaling in plants is involved in regulating development,1,2 ensuring cross pollination through initiation of self-incompatibility4 and assisting with recognition of beneficial (nitrogen fixing bacteria5) or unfavorable organisms (pathogens6 or herbivores7). Peptides function to help plants to respond to a changing environment and improve their chances of survival. Constitutive expression of the gene encoding a novel cysteine rich peptide TAXIMIN1 (TAX1) resulted in fusion of lateral organs and in abnormal fruit morphology. TAX1 signaling functions independently from transcription factors known to play a role in this process such as LATERAL ORGAN FUSION1 (LOF1). Here, we report that the TAX1 promoter is not induced by the LOF1 transcription factor and that the TAX1 peptide neither interferes with transcriptional activation by LOF1.1 or transcriptional repression by LOF1.2. Furthermore, we found that TAX1 overexpressing lines were hypersensitive to continuous light, which may be reflected by a decreased accumulation of the UV-B protecting compound sinapoyl-malate. Finally, adding the antibiotic cefotaxime to the medium surprisingly countered the light hypersensitivity phenotype of TAX1 overexpressing seedlings. PMID:26967827

  2. Hypersensitivity to fluoroquinolones

    PubMed Central

    Fernández, Tahia D.; Ariza, Adriana; Palomares, Francisca; Montañez, María I.; Salas, María; Martín-Serrano, Angela; Fernández, Rubén; Ruiz, Arturo; Blanca, Miguel; Mayorga, Cristobalina; Torres, María J.

    2016-01-01

    Abstract Although fluoroquinolones (FQs) are generally well-tolerated antibiotics, increasing numbers of hypersensitivity reactions have been reported. These can be evaluated in vitro by basophil activation tests (BATs); however, sensitivity is not optimal. Many factors could influence sensitivity such as basophil activation markers. The objective of this study was to evaluate the influence of 2 different activations markers, CD63 and CD203c, on the sensitivity of BAT to FQ. We studied 17 patients with immediate allergic reactions to FQ. BAT was performed with moxifloxacin and ciprofloxacin using CD193 (CCR3) for basophil selection and CD203c or CD63 as activation markers. Stimulation with ciprofloxacin induced a significantly higher expression of CD63 in ciprofloxacin-allergic patients compared to moxifloxacin-allergic patients (P = 0.002). In patients allergic to moxifloxacin with anaphylactic shock, we have observed an increase in the percentage of cells that upregulate CD203c, whereas patients with anaphylaxis preferentially upregulate CD63. The best sensitivity–specificity was obtained using a cutoff of 3 and the culprit FQ, using CD203c for moxifloxacin-allergic patients (sensitivity = 36.4%; specificity = 94.4%), and CD63 for ciprofloxacin-allergic patients (sensitivity = 83.3%; specificity = 88.9%). A negative correlation was found between the upregulation of CD63 and CD203c and the time interval between the reaction occurrence and the performance of the test (Spearman r = −0.446; P < 0.001 for CD63 and Spearman r = −0.386; P < 0.001 for CD203c). The performance of BAT for FQ allergy must be optimized for each drug, taking into account possible differences in the stimulation mechanism that leads to the upregulation of different activation markers. PMID:27281069

  3. 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.

  4. [A case of pneumonitis due to serrapeptase].

    PubMed

    Hirahara, K; Saitoh, T; Terada, I; Uno, K; Nagai, A; Kioi, S; Arakawa, M

    1989-10-01

    A case of pneumonitis due to Serrapeptase was described. A 69-year-old man was treated with Serrapeptase for 16 days because of common cold, then fever, nonproductive cough and dyspnea developed and chest X-ray revealed diffuse fine granular shadows in bilateral lung fields. Once the administration of Serrapeptase was halted, symptoms, chest X-ray abnormalities and laboratory data improved markedly. The fraction of lymphocytes increased in bronchoalveolar lavage fluid and OKT4/T8 decreased. Microscopic examination of transbronchial lung biopsy showed interstitial pneumonia. Both leukocyte migration inhibition test and sensitized hemagglutination test were positive for Serrapeptase. Based on these findings, we diagnosed this case as Serrapeptase-induced pneumonitis.

  5. Clinical spectrum of cryptogenic organising pneumonitis.

    PubMed Central

    Bellomo, R; Finlay, M; McLaughlin, P; Tai, E

    1991-01-01

    Cryptogenic organising pneumonitis (bronchiolitis obliterans organising pneumonia) is an uncommon condition that often responds to steroids. It is characterised clinically by constitutional symptoms, pathologically by intra-alveolar organising fibrosis, and radiologically by patchy pulmonary infiltrates. Its full clinical spectrum and course are only partially described and understood. Six patients are described, seen over three years, with considerably diverse clinical and radiological presentations (two had diffuse lung infiltrates, two had peripheral lung infiltrates, and two had localised lobar involvement) and with very varying severity of disease (two with a life threatening illness, three with appreciable subacute constitutional symptoms, and one with mild symptoms). It is concluded that cryptogenic organising pneumonitis can present in various ways. A set of diagnostic criteria are proposed which will help in the recognition of this syndrome, which is probably underdiagnosed. Images PMID:1926023

  6. Electrosensibility and electromagnetic hypersensitivity.

    PubMed

    Leitgeb, Norbert; Schröttner, Jörg

    2003-09-01

    Electromagnetic sensibility, the ability to perceive electric and electromagnetic exposure, and electromagnetic hypersensitivity (EHS), developing health symptoms due to exposure to environmental electromagnetic fields, need to be distinguished. Increased electrosensibility is a necessary, however, not a sufficient condition for electromagnetic hypersensitivity. At an extended sample of the general population of 708 adults, including 349 men and 359 women aged between 17 and 60 years, electrosensibility was investigated and characterized by perception threshold and its standard deviation. By analyzing the probability distributions of the perception threshold of electric 50 Hz currents, evidence could be found for the existence of a subgroup of people with significantly increased electrosensibility (hypersensibility) who as a group could be differentiated from the general population. The presented data show that the variation of the electrosensibility among the general population is significantly larger than has yet been estimated by nonionizing radiation protection bodies, but much smaller than claimed by hypersensitivity self-aid groups. These quantitative results should contribute to a less emotional discussion of this problem. The investigation method presented, is capable of exclusion diagnostics for persons suffering from the hypersensitivity syndrome. PMID:12929157

  7. Diclofenac (Voltaren)-induced pneumonitis after chest operation.

    PubMed

    Ueda, Kazuhiro; Sakano, Hisashi; Tanaka, Toshiki; Hayashi, Masatarou; Fujita, Nobuhiro; Zempo, Nobuya

    2002-12-01

    We report a rare case of nonsteroidal anti-inflammatory drug-induced pneumonitis in a 72-year-old man taking diclofenac for wound pain after pulmonary resection. The pneumonitis and pleural effusion were predominant on the operative side and resolved rapidly after the diclofenac was discontinued. The diagnosis of drug-induced pneumonitis was based on a lymphocyte stimulation test that was positive for diclofenac sodium and negative for other drugs. This case report demonstrated that surgeons should be aware of the possibility of pneumonitis induced by a nonsteroidal anti-inflammatory drug.

  8. Thin-Section CT Characteristics and Longitudinal CT Follow-up of Chemotherapy Induced Interstitial Pneumonitis

    PubMed Central

    Lee, Han Na; Kim, Mi Young; Koo, Hyun Jung; Kim, Sung-Soo; Yoon, Dok Hyun; Lee, Jae Cheol; Song, Jin Woo

    2016-01-01

    Abstract To describe the computed tomography (CT) features of chemotherapy-induced interstitial pneumonitis (CIIP) with longitudinal follow-up. The study was approved by the local ethics committee. One hundred consecutive patients with CIIP between May 2005 and March 2015 were retrospectively enrolled. The initial CT was reviewed by 2 independent chest radiologists and categorized into 1 of 4 CT patterns in accordance with the 2013 guidelines for idiopathic interstitial pneumonia: nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), hypersensitivity pneumonitis (HP) mimicking desquamative interstitial pneumonitis, and diffuse alveolar damage (DAD). We assessed semiquantitative analysis on a 5% scale to assess the extent of parenchymal abnormalities (emphysema, reticulation, ground-glass opacity, consolidation, honeycombing cyst) and their distribution on initial (n = 100), subsequent (n = 87), and second follow-up CT (n = 48). Interval changes in extent on follow-up CT were compared using paired t test. The clinic-radiologic factors were compared between Group 1 (NSIP and OP patterns) and Group 2 (HP and DAD patterns) using χ2 and independent t tests. The most common pattern of CIIP on the initial CT was HP (51%), followed by NSIP (23%), OP (20%), and DAD (6%). Diffuse ground-glass opacity was the most common pulmonary abnormality. The predominant distribution was bilateral (99%) and symmetric (82%), with no craniocaudal (60%) or axial (79%) dominance. Subsequent and second follow-up CTs showed decreased extent of total pulmonary abnormalities (P < 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

  9. Histopathological Characterization of Cutaneous Delayed-type Hypersensitivity and Correlations with Intestinal Pathology and Systemic Immune Responses in Sheep with Paratuberculosis.

    PubMed

    Gulliver, E L; Plain, K M; Begg, D J; Whittington, R J

    2015-01-01

    Cell-mediated immunity has been exploited historically in the diagnosis of mycobacterial diseases through elicitation of a delayed-type hypersensitivity (DTH) reaction following intradermal injection of an antigen. Here we describe the histopathological features of the cutaneous DTH reaction and its association with intestinal pathology and systemic immune responses in sheep with Mycobacterium avium subspecies paratuberculosis (MAP) infection. A mixed mononuclear cellular infiltrate dominated the DTH reaction and was present in perivascular and periadnexal patterns. Multiple multinucleate giant cells were present in the cellular infiltrate in one sheep while plasma cells were an obvious feature in six others. Sheep with paucibacillary intestinal lesions had the greatest degrees of cutaneous induration, more severe cellular infiltration in DTH lesions and high systemic interferon (IFN)-γ production. In contrast, sheep with multibacillary intestinal lesions, and particularly those with dissemination of MAP to extra-intestinal tissues, had minimal cutaneous induration, nil to mild cellular infiltration in DTH lesions and high serum anti-MAP antibody levels. Systemic IFN-γ production generally was augmented following skin sensitization. In general, the gross and histopathological features of the cutaneous DTH response matched the stage of paratuberculosis reflected by intestinal pathology and systemic measures of humoral and cellular immunity.

  10. Pharmacogenetics of drug hypersensitivity

    PubMed Central

    Phillips, Elizabeth J; Mallal, Simon A

    2010-01-01

    Drug hypersensitivity reactions and severe cutaneous adverse drug reactions, such as Stevens–Johnson syndrome and toxic epidermal necrolysis, are examples of serious adverse drug reactions mediated through a combination of metabolic and immunological mechanisms that could traditionally not have been predicted based on the pharmacological characteristics of the drug alone. The discovery of new associations between these syndromes and specific HLA has created the promise that risk for these reactions could be predicted through pharmacogenetic screening, thereby avoiding serious morbidity and mortality associated with these types of drug reactions. Despite this, several hurdles exist in the translation of these associations into pharmacogenetic tests that could be routinely used in the clinical setting. HLA-B*5701 screening to prevent abacavir hypersensitivity syndrome is an example of a test now in widespread routine clinical use in the developed world. PMID:20602616

  11. [Electromagnetic fields hypersensitivity].

    PubMed

    Sobiczewska, Elzbieta; Szmigielski, Stanisław

    2009-01-01

    The development of industry, particularly of new technologies in communication systems, gives rise to the number and diversty of electromagnetic field (EMF) sources in the environment. These sources, including power-frequent, radiofrequent and microwaves, make human life richer, safer and easier. But at the same time, there is growing concern about possible health risks connected with EMF exposure. An increasing number of persons have recently reported on a variety of health problems induced, in their opinion, by exposure to EMF. It is important to note that EMF levels to which these individuals are exposed are generally well below the recommended exposure limits and are certainly far below those known to produce any adverse effects. These persons call themselves "electromagnetic hypersensitivity individuals" And complain about experiencing various types of non-specific symptoms, including dermatological, neurological and vegetative. In the present paper, the problem of electromagnetic hypersensitivity phenomenon is discussed based on the recently published literature.

  12. Dentin Hypersensitivity and Oxalates

    PubMed Central

    Cunha-Cruz, J.; Stout, J.R.; Heaton, L.J.; Wataha, J.C.

    2011-01-01

    Treatment of dentin hypersensitivity with oxalates is common, but oxalate efficacy remains unclear. Our objective was to systematically review clinical trials reporting an oxalate treatment compared with no treatment or placebo with a dentin hypersensitivity outcome. Risk-of-bias assessment and data extraction were performed independently by two reviewers. Standardized mean differences (SMD) were estimated by random-effects meta-analysis. Of 677 unique citations, 12 studies with high risk-of-bias were included. The summary SMD for 3% monohydrogen-monopotassium oxalate (n = 8 studies) was -0.71 [95% Confidence Interval: -1.48, 0.06]. Other treatments, including 30% dipotassium oxalate (n = 1), 30% dipotassium oxalate plus 3% monohydrogen monopotassium oxalate (n = 3), 6% monohydrogen monopotassium oxalate (n = 1), 6.8% ferric oxalate (n = 1), and oxalate-containing resin (n = 1), also were not statistically significantly different from placebo treatments. With the possible exception of 3% monohydrogen monopotassium oxalate, available evidence currently does not support the recommendation of dentin hypersensitivity treatment with oxalates. PMID:21191127

  13. [Food hypersensitivity in children].

    PubMed

    Kolacek, Sanja

    2011-01-01

    Food hypersensitivity affects children and adults with an increasing prevalence, and is therefore an important public health problem in the majority of developed countries. Moreover, self-reported reactions to food are of several times higher prevalence, compared to hypersensitivity diagnosed following well established evidence-based diagnostic guidelines. In children, allergic food reactions are more common compared to non-allergic food hypersensitivity reactions, and 90% of them are caused with only 8 food allergens: cow's milk, soya, egg, fish, shellfish, peanut, tree-nuts and gluten. Diagnosis should be based on challenge tests with the potentially offending food allergens. Concerning other, more conservative diagnostic procedures, negative serology and negative skin-prick tests can exclude IgE-mediated food allergy, but positive tests, due to high rate of false positive reactions are not sufficient for diagnosis. Strict dietary avoidance of incriminated allergens is the only well established management strategy. However, this should be applied only if food allergy is well documented - following the exposition tests. Introducing elimination diet in a paediatric population, particularly with the elimination of multiple foods, could cause inappropriate growth and disturb organ maturation. Concerning allergy prevention, avoidance of allergens is not efficacious either during pregnancy and lactation or weaning period, and is therefore, not recommended neither as a population preventive measure, nor in children at risk.

  14. 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.

  15. Azacitidine-associated acute interstitial pneumonitis.

    PubMed

    Kuroda, Junya; Shimura, Yuji; Mizutani, Shinsuke; Nagoshi, Hisao; Kiyota, Miki; Chinen, Yoshiaki; Maegawa, Saori; Kobayashi, Tsutomu; Matsumoto, Yosuke; Horiike, Shigeo; Taniwaki, Masafumi

    2014-01-01

    Azacitidine is the first-line therapeutic option for myelodysplastic syndrome (MDS). This report describes a case of MDS in a patient who developed fatal acute interstitial pneumonitis (AIP) after the first seven-day course of intravenous azacitidine (75 mg/m(2)/day) treatment. A review of previous and present studies of azacitidine-associated AIP suggests that azacitidine may cause life-threatening AIP during or after the first seven-day course of treatment, with pyrexia commonly preceding AIP. Although the non-hematologic adverse events associated with azacitidine are generally relatively mild, further accumulation of evidence may help to make an earlier diagnosis of azacitidine-associated AIP.

  16. [Nonallergic hypersensitivity to environmental factors].

    PubMed

    Rakhmanin, Iu A; Fedoseeva, V N; Makovetskaia, A K; Fedoskova, T G

    2013-01-01

    The prevalence and severity of manifestations of non-allergic hypersensitivity to chemical environmental factors pose the question about the need to study the mechanisms of its formation in population. It should be borne in mind that, in the absence of immunological mechanisms of formation of the mentioned state, the term "chemical sensitization" must be replaced by the term "non-allergic hypersensitivity." The investigation of this problem should permit to reduce the risk of formation of different types of hypersensitivity in population.

  17. Asymmetrical hypersensitivity to bovine collagen.

    PubMed

    Somerville, P; Wray, R C

    1993-05-01

    We report a unique patient with true asymmetrical hypersensitivity to bovine collagen. Hypersensitivity is the development of an inflammatory response at a treatment site after a negative skin test. She developed an inflammatory response in only one of two simultaneously injected sites. About 1.5% of patients with a negative skin test have a hypersensitivity reaction consisting of firmness, erythema, and swelling. The signs and symptoms generally resolve spontaneously in a few months.

  18. Acute allergic interstitial pneumonitis induced by hydrochlorothiazide.

    PubMed Central

    Biron, P; Dessureault, J; Napke, E

    1991-01-01

    OBJECTIVE: To examine the clinical features of 4 unpublished cases and 26 published cases of acute allergic interstitial pneumonitis induced by hydrochlorothiazide (HCT). DATA SOURCES: The unpublished cases were found in the database of the Drug Adverse Reaction Program, Health Protection Branch, Department of National Health and Welfare, and the database of the Programme conjoint de pharmacovigilance, in Quebec. The published cases were retrieved from MEDLINE and EMBASE. STUDY SELECTION: Reported cases were selected if they were sufficiently documented. All published cases were selected because a differential diagnosis had been made in each one. DATA SYNTHESIS: The onset was acute and dramatic; the average time to onset of symptoms was 44 minutes. Sex was a predominant risk factor, since 27 (90%) of the 30 patients were women. The average age was 56 years; thus, most of the women were postmenopausal. Over two-thirds of the patients had one to three positive prechallenges or rechallenges, 3 of the 52 documented adverse events occurred after a voluntary rechallenge, some were life-threatening and necessitated mechanical ventilation, and 1 was fatal. Treatment was supportive; avoidance of HCT was the only prevention. CONCLUSION: Acute allergic interstitial pneumonitis due to HCT is extremely rare and potentially fatal. Such a reaction can be diagnosed only if the clinician suspects it when presented with a case of unexplained acute pulmonary edema. PMID:2049694

  19. Laryngeal hypersensitivity in chronic cough.

    PubMed

    Hull, J H; Menon, A

    2015-12-01

    Patients with chronic cough often report symptoms arising in the throat, in response to non-specific stimuli. Accordingly, the concept of a 'hypersensitivity' of the larynx in chronic cough has evolved over the past ten years. Patients with cough and laryngeal hypersensitivity frequently report features that overlap other laryngeal dysfunction syndromes, including a tendency for the vocal cords to inappropriately adduct. The mechanisms underlying laryngeal hypersensitivity in chronic cough are currently unclear, however recent studies provide new clinical and physiological techniques to aid detection and monitoring of laryngeal hypersensitivity. This review provides an overview of the current state of knowledge in this field.

  20. Anticonvulsant hypersensitivity syndrome.

    PubMed

    Morkunas, A R; Miller, M B

    1997-10-01

    Anticonvulsant hypersensitivity syndrome (AHS) is an uncommon but potentially fatal adverse effect that can occur from exposure to phenytoin, carbamazepine, or phenobarbital. It has diverse clinical features and a variable presentation which results in a delay in making the diagnosis. The syndrome commonly begins within 3 weeks after initiation of an anticonvulsant. Patients typically present with a constellation of fever, usually followed by the development of a rash of variable severity and type, and lymphadenopathy. In patients presenting with these features, the clinician should have a high index of suspicion for AHS. PMID:9330838

  1. Pasteurella haemolytica antigens associated with resistance to pneumonic pasteurellosis.

    PubMed Central

    Mosier, D A; Simons, K R; Confer, A W; Panciera, R J; Clinkenbeard, K D

    1989-01-01

    Antigens associated with whole Pasteurella haemolytica biotype A serotype 1, a capsular carbohydrate-protein extract of the organism, and P. haemolytica leukotoxin were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antigens of the electrophoresed preparations were detected by Western blotting (immunoblotting) with sera from cattle which were either nonvaccinated or vaccinated with live or killed P. haemolytica vaccines and had variable degrees of resistance to experimental pneumonic pasteurellosis. Distinct, easily recognizable antigens of these preparations were identified, and the antibody responses to these antigens were quantified by densitometry. To determine their importance to disease resistance, we then compared antibody responses with experimental lesion scores. Antibody reactivity to surface antigens which were significantly correlated with resistance and present in two or more of the preparations were detected at 86, 66, 51, 49, 34, 31, and 16 kilodaltons (kDa). Of these, antibody responses to antigens at 86, 49, and 31 kDa appeared most important based on their concentration and significance levels. Antibody reactivity to leukotoxin antigens which were significantly correlated with resistance and common with important surface antigens were detected at 86, 66, and 49 kDa. Antibody responses to unique leukotoxin antigens which were significantly correlated with resistance were present at 92 and 58 kDa. Images PMID:2917783

  2. Drug hypersensitivity syndrome.

    PubMed

    Kumari, Rashmi; Timshina, Dependra K; Thappa, Devinder Mohan

    2011-01-01

    Drug hypersensitivity syndrome (DHS) is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs), viz., phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

  3. Pneumonic plague outbreak, Northern Madagascar, 2011.

    PubMed

    Richard, Vincent; Riehm, Julia M; 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.

  4. Delayed drug hypersensitivity reactions.

    PubMed

    Pichler, Werner J

    2003-10-21

    Immune reactions to small molecular compounds, such as drugs, can cause a variety of diseases involving the skin, liver, kidney, and lungs. In many drug hypersensitivity reactions, drug-specific CD4+ and CD8+ T cells recognize drugs through their alphabeta T-cell receptors in an MHC-dependent way. Drugs stimulate T cells if they act as haptens and bind covalently to peptides or if they have structural features that allow them to interact with certain T-cell receptors directly. Immunohistochemical and functional studies of drug-reactive T cells in patients with distinct forms of exanthema reveal that distinct T-cell functions lead to different clinical phenotypes. In maculopapular exanthema, perforin-positive and granzyme B-positive CD4+ T cells kill activated keratinocytes, while a large number of cytotoxic CD8+ T cells in the epidermis is associated with formation of vesicles and bullae. Drug-specific T cells also orchestrate inflammatory skin reactions through the release of various cytokines (for example, interleukin-5, interferon) and chemokines (such as interleukin-8). Activation of T cells with a particular function seems to lead to a specific clinical picture (for example, bullous or pustular exanthema). Taken together, these data allow delayed hypersensitivity reactions (type IV) to be further subclassified into T-cell reactions, which through the release of certain cytokines and chemokines preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd). Moreover, cytotoxic functions by either CD4+ or CD8+ T cells (type IVc) seem to participate in all type IV reactions.

  5. STUDIES ON HYPERSENSITIVITY

    PubMed Central

    Gell, P. G. H.; Benacerraf, B.

    1961-01-01

    In earlier observations with the picryl system, it was concluded that contact sensitivity was a form of delayed (cellular) hypersensitivity to conjugates of sensitizer with autologous proteins indistinguishable in its immunological mechanism from other classical forms of delayed hypersensitivity to proteins. This conclusion has been confirmed and extended with the picryl and chlorbenzoyl chloride systems. 1. It is shown that to induce a state of contact sensitivity, the minimal necessary amounts of hapten are of the same order of magnitude, whether this hapten is conjugated with protein or the free reactive chemical itself. From this, it is evident that contamination of conjugates with small amounts of unreacted sensitizer plays no part in the induction of contact reactivity by the conjugate. With the dinitrophenyl system, no contact sensitivity could be induced by the conjugates used; possible reasons for this discrepancy are discussed. 2. Animals sensitized to contact by homologous conjugate can be completely desensitized by injections of such a conjugate in large amount; a similar injection schedule has no effect on the contact sensitivity of animals sensitized with the free reactive sensitizer. 3. The capacity of heterologous (ovalbumin) conjugates to evoke anti-hapten antibodies is shown to be greater than that of homologous (guinea pig seralbumin) conjugates: the reverse is true of their capacity to induce delayed reactivity. 4. Evidence is brought forward to suggest that in animals sensitized with homologous albumin conjugates, the specificity of the delayed reaction involves more than the hapten alone, even though the carrier protein is non-antigenic on its own. The contrast with the apparent lesser specificity of the antibodies later produced is discussed. PMID:13704282

  6. Sulfite hypersensitivity. A critical review

    SciTech Connect

    Gunnison, A.F.; Jacobsen, D.W.

    1987-01-01

    Sulfiting agents (sulfur dioxide and the sodium and potassium salts of bisulfite, sulfite, and metabisulfite) are widely used as preservatives in foods, beverages, and pharmaceuticals. Within the past 5 years, there have been numerous reports of adverse reactions to sulfiting agents. This review presents a comprehensive compilation and discussion of reports describing reactions to ingested, inhaled, and parenterally administered sulfite. Sulfite hypersensitivity is usually, but not exclusively, found within the chronic asthmatic population. Although there is some disagreement on its prevalence, a number of studies have indicated that 5 to 10% of all chronic asthmatics are sulfite hypersensitive. This review also describes respiratory sulfur dioxide sensitivity which essentially all asthmatics experience. Possible mechanisms of sulfite hypersensitivity and sulfur dioxide sensitivity are discussed in detail. Sulfite metabolism and the role of sulfite oxidase in the detoxification of exogenous sulfite are reviewed in relationship to the etiology of sulfite hypersensitivity. 147 references.

  7. 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

  8. Hypersensitivity to antineoplastic agents.

    PubMed

    Castells, M C

    2008-01-01

    The need to offer first line therapy for primary and recurrent cancers has spurred the clinical development of rapid desensitizations for chemotherapy and monoclonal antibodies. Rapid desensitizations allow patients to be treated with medications to which they have presented with hypersensitivity reactions (HSRs), including anaphylaxis. Rapid desensitization achieves temporary tolerization to full therapeutic doses by slow administration of incremental doses of the drug inducing the HSR. Protocols are available for most chemotherapy agents, including taxanes, platins, doxorubicin, monoclonal antibodies, and others. Candidate patients include those who present with type I HSRs, mast cell/IgE dependent, including anaphylaxis, and non-IgE mediated HSRs, during the chemotherapy infusion or shortly after. Idiosyncratic reactions, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis are not amenable to rapid desensitization. The recommendation for rapid desensitization can only be made by allergy and immunology specialists and can only be performed in settings with one-to-one nurse-patient care and where resuscitation personnel and resources are readily available. Repeated desensitizations can be safely performed in outpatient settings with similar conditions, which allow cancer patients to remain in clinical studies. We have generated a universal 12-step protocol that was applied to 413 cases of intravenous and intraperitoneal rapid desensitizations using taxanes, platins, liposomal doxorubicin, doxorubicin, rituximab, and other chemotherapy drugs. Under this protocol all patients were able to complete their target dose, and 94% of the patients had limited or no reactions. No deaths or codes were reported, indicating that the procedure was safe and effective in delivering first line chemotherapy drugs. PMID:18991707

  9. Nilutamide pneumonitis: a report on eight patients.

    PubMed Central

    Pfitzenmeyer, P; Foucher, P; Piard, F; Coudert, B; Braud, M L; Gabez, P; Lacroix, S; Mabille, J P; Camus, P

    1992-01-01

    BACKGROUND: Nilutamide is a new, specific synthetic antiandrogen, released in several countries for the treatment of metastatic carcinoma of the prostate. Eight patients at the University Medical Centre at Dijon and affiliated referring hospitals developed reversible pulmonary opacities and respiratory symptoms while taking the drug. METHODS: Records of eight patients who developed new, otherwise unexplained chest opacities while taking nilutamide were reviewed. In each patient a careful aetiological search was made for other environmental or endogenous causes. Six patients underwent bronchoalveolar lavage, and lavage fluid was cultured. Corticosteroids were not given, unless gas exchange was compromised (two patients). RESULTS: The eight patients (all male) had had carcinoma of the prostate diagnosed on average 10.2 months earlier. All had improved with nilutamide, with a dramatic decrease of prostate specific antigen levels. Seven had received nilutamide at the recommended dosage of 150 mg/day, and one had received twice that amount. Treatment had lasted on average 113 (range 10-225) days, and the mean cumulated exposure was 21.8 (3-38) grams. The chest radiographs showed bilateral infiltrates, with no consistent topographic predilection. A restrictive lung defect was present in six patients and hypoxia in all (mean arterial oxygen tension (PaO2) 6.6 kPa). Bronchoalveolar lavage showed lymphocytosis in four patients and neutrophilia in two. The outcome was favourable in all patients after they had stopped nilutamide only (five patients), with corticosteroids (two patients) or a simple reduction of nilutamide from 300 to 150 mg/day (one patient). Recovery was associated with improvement of pulmonary function and PaO2. CONCLUSION: Nilutamide is associated with interstitial pneumonitis in about 1% of patients and appears reversible. Images PMID:1412120

  10. Immediate hypersensitivity reaction with mango.

    PubMed

    Shah, Ashok; Gera, Kamal

    2014-01-01

    Hypersensitivity to the fruit mango is extremely rare and can exhibit either as immediate or delayed reactions. Since 1939, only 22 patients (10 with immediate type I reactions and 12 with delayed) have been documented with allergy to mango. History of atopy and geographical region may influence the type of reaction. Immediate reactions occurred most often in patients with history of atopy, while delayed reactions developed in non-atopic individuals. Clustering of delayed hypersensitivity reports from Australia and immediate reactions from Europe has been documented. We report a 50-year-old man with immediate type I hypersensitivity to mango, who developed cough, wheezing dyspnoea, generalised itching and abdominal discomfort after ingestion of mango. Life threatening event can also happen making it imperative to diagnose on time, so as to prevent significant morbidity and potential mortality. PMID:25133813

  11. Dentin hypersensitivity and its management.

    PubMed

    Chu, C H; Lam, Anty; Lo, Edward C M

    2011-01-01

    Dentin hypersensitivity is a common patient complaint that is more prevalent than the profession realizes. It is important for dentists to diagnose dentin hypersensitivity by exclusion and provide appropriate treatment recommendations for patients. Various treatment methods have been proposed but no universally accepted desensitizing agent or treatment has been identified. When a patient has symptoms that can be attributed to dentin hypersensitivity, a thorough clinical examination should be carried out to rule out other likely causes prior to diagnosis and treatment. Depending on the identified cause, a combination of individualized instructions on proper oral health behaviors, use of at-home products, and professional treatment may be required to manage the problem. PMID:21903521

  12. Hypersensitivity to Parietaria officinalis pollen in newcomers to the area with the plant.

    PubMed

    Cvitanović, S; Marusić, M; Juricić, M; Vrdoljak, E; Petrovecki, M; Rozga, A; Stavljenić-Rukavina, A

    1993-11-01

    Hypersensitivity to Parietaria officinalis (wall pellitory) pollen and other environmental allergens was studied in pollinosis patients allergic to P. officinalis pollen who were born in areas without P. officinalis and later moved to the city of Split, where P. officinalis is responsible for some 65% of pollinosis cases. Highly significant positive correlations were found for both the intensity of skin test reaction and concentration of specific serum IgE with the length of residence in the area. In contrast, the respective data on subjects hypersensitive to P. officinalis pollen allergen, but born and living in the area of Split, revealed a tendency to negative correlation between age and intensity of hypersensitivity to P. officinalis. A number of patients from both groups were tested for presence of serum IgE antibodies specific for 14 common environmental allergens. Hypersensitivity to P. officinalis pollen was associated with hypersensitivity to olive, mugwort, and birch pollen in newcomers; hypersensitivity to birch and, to some extent, olive pollen was significantly more frequent in newcomers than in autochthonous patients who were allergic to P. officinalis pollen. Regardless of whether the patients were autochthons or newcomers to the area with P. officinalis, hypersensitivity to P. officinalis mostly excluded hypersensitivity to Dermatophagoides farinae and D. pteronyssinus, and vice versa.

  13. 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

  14. Capnocytophaga cynodegmi Cellulitis, Bacteremia, and Pneumonitis in a Diabetic Man

    PubMed Central

    Sarma, Podila S.; Mohanty, Smruti

    2001-01-01

    Capnocytophaga cynodegmi (formerly “DF-2 like organism”), a commensal organism of the canine oral cavity, is a capnophilic, gram-negative, facultative bacillus. C. cynodegmi has rarely been encountered in human diseases. We report the first known case of cellulitis, bacteremia, and pneumonitis caused by C. cynodegmi in a diabetic man from central India following a dog bite. PMID:11326042

  15. 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.

  16. 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

  17. Structural basis of metal hypersensitivity

    PubMed Central

    Wang, Yang

    2014-01-01

    Metal hypersensitivity is a common immune disorder. Human immune systems mount the allergic attacks on metal ions through skin contacts, lung inhalation and metal-containing artificial body implants. The consequences can be simple annoyances to life-threatening systemic illness. Allergic hyper-reactivities to nickel (Ni) and beryllium (Be) are the best-studied human metal hypersensitivities. Ni-contact dermatitis affects 10 % of the human population, whereas Be compounds are the culprits of chronic Be disease (CBD). αβ T cells (T cells) play a crucial role in these hypersensitivity reactions. Metal ions work as haptens and bind to the surface of major histocompatibility complex (MHC) and peptide complex. This modifies the binding surface of MHC and triggers the immune response of T cells. Metal-specific αβ T cell receptors (TCRs) are usually MHC restricted, especially MHC class II (MHCII) restricted. Numerous models have been proposed, yet the mechanisms and molecular basis of metal hypersensitivity remain elusive. Recently, we determined the crystal structures of the Ni and Be presenting human MHCII molecules, HLA-DR52c (DRA*0101, DRB3*0301) and HLA-DP2 (DPA1*0103, DPB1*0201). These structures revealed unusual features of MHCII molecules and shed light on how metal ions are recognized by T cells. PMID:22983897

  18. Occupational asthma due to esparto hypersensitivity in a building worker.

    PubMed

    Ruiz-Hornillos, Francisco Javier; De Barrio Fernández, Manuel; Molina, Pilar Tornero; Marcén, Itziar Sánchez; Fernandez, Galicia Davila; Sotés, María Rubio; de Ocariz, María Luisa Baeza Ochoa

    2007-01-01

    Esparto is a gramineous plant that has multiple applications in today's industry. Several cases of hypersensitivity pneumonitis (HP) caused by esparto inhalation have been reported, but only one case of asthma caused by Aspergillus fumigatus contaminating esparto has been communicated. We report a case of asthma induced by esparto inhalation in a 58-year-old man, who is a building industry worker, with subclinical sensitization to grass pollen. The relation between clinical symptoms and work activities was supported by peak expiratory flow (PEF) monitorization; PEF values decreased by 20% the days he handled esparto. Prick test with esparto was positive. Immunoblot analysis revealed several allergens in the esparto extract, some of them present in Lolium and A. fumigatus extracts. IgE immunoblot inhibition revealed a complete inhibition of lolium and A. fumigatus IgE reactive bands by esparto proteins. The patient then avoided the exposure to esparto at work and has remained asymptomatic for the last 2 years. In conclusion, this is a case of occupational asthma caused by esparto dust mediated by IgE antibodies. Proteins of A. fumigatus as well as proteins from this gramineous plant, which cross-reacted with esparto allergens, were responsible for the disease.

  19. Drug hypersensitivity reactions involving skin.

    PubMed

    Hausmann, Oliver; Schnyder, Benno; Pichler, Werner J

    2010-01-01

    Immune reactions to drugs can cause a variety of diseases involving the skin, liver, kidney, lungs, and other organs. Beside immediate, IgE-mediated reactions of varying degrees (urticaria to anaphylactic shock), many drug hypersensitivity reactions appear delayed, namely hours to days after starting drug treatment, showing a variety of clinical manifestations from solely skin involvement to fulminant systemic diseases which may be fatal. Immunohistochemical and functional studies of drug-specific T cells in patients with delayed reactions confirmed a predominant role for T cells in the onset and maintenance of immune-mediated delayed drug hypersensitivity reactions (type IV reactions). In these reactions, drug-specific CD4+ and CD8+ T cells are stimulated by drugs through their T cell receptors (TCR). Drugs can stimulate T cells in two ways: they can act as haptens and bind covalently to larger protein structures (hapten-carrier model), inducing a specific immune response. In addition, they may accidentally bind in a labile, noncovalent way to a particular TCR of the whole TCR repertoire and possibly also major histocompatibility complex (MHC)-molecules - similar to their pharmacologic action. This seems to be sufficient to reactivate certain, probably in vivo preactivated T cells, if an additional interaction of the drug-stimulated TCR with MHC molecules occurs. The mechanism was named pharmacological interaction of a drug with (immune) receptor and thus termed the p-i concept. This new concept may explain the frequent skin symptoms in drug hypersensitivity to oral or parenteral drugs. Furthermore, the various clinical manifestations of T cell-mediated drug hypersensitivity may be explained by distinct T cell functions leading to different clinical phenotypes. These data allowed a subclassification of the delayed hypersensitivity reactions (type IV) into T cell reactions which, by releasing certain cytokines and chemokines, preferentially activate and recruit

  20. 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

  1. 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

  2. Food hypersensitivity in a cat.

    PubMed

    Medleau, L; Latimer, K S; Duncan, J R

    1986-09-15

    Food hypersensitivity was diagnosed in a 4-year-old Siamese cat. Clinical signs included intense erythema, with alopecia, excoriations, erosions, and crusts involving the ventral portion of the abdomen, inguinal region, medial aspect of each thigh, and cranial and lateral aspects of all 4 limbs. The cat was intensely pruritic. Histologically, there was cutaneous mast cell hyperplasia and diffuse infiltration of eosinophils in the dermis. Blood eosinophilia also was found. Clinical signs resolved after exclusive feeding of a hypoallergenic diet.

  3. 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.

  4. Genotyping for Severe Drug Hypersensitivity

    PubMed Central

    Karlin, Eric; Phillips, Elizabeth

    2014-01-01

    Over the past decade, there have been significant advances in our understanding of the immunopathogenesis and pharmacogenomics of severe immunologically-mediated adverse drug reactions. Such T-cell-mediated adverse drug reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced liver disease (DILI) and other drug hypersensitivity syndromes have more recently been shown to be mediated through interactions with various class I and II HLA alleles. Key examples have included the associations of HLA-B*15:02 and carbamazepine induced SJS/TEN in Southeast Asian populations and HLA-B*57:01 and abacavir hypersensitivity. HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation. Ultimately, our increased understanding of the interaction between drugs and the MHC could be used to inform drug design and drive pre-clinical toxicity programs to improve drug safety. PMID:24429903

  5. Experimental pneumonitis induced by Naegleria fowleri in mice.

    PubMed

    Willaert, E; Stevens, A R

    1980-01-01

    An environmental Naegleria isolate, from a cooling lake receiving thermal additions from an electric power plant, caused both primary amoebic meningoencephalitis (PAM) and pneumonitis in mice after intranasal inoculation. Amoebae, recovered from brains and lungs of mice inoculated with the environmental isolate, produced both brain and lung infections in repeated mouse passages. Electron microscope examination of infected lungs revealed a moderate inflammatory reaction with slight necrosis. Amoebae re-isolated from mice with PAM and pneumonitis were identified as N. fowleri by the indirect immuno-fluorescent antibody technique using anti-N. fowleri serum. The results suggest that in addition to PAM, N. fowleri may be capable of causing subacute and acute respiratory infections in man.

  6. 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.

  7. Hypersensitivity syndrome caused by amitriptyline administration

    PubMed Central

    Milionis, H.; Skopelitou, A.; Elisaf, M.

    2000-01-01

    Adverse cutaneous manifestations are among the most common side effects associated with psychotropic drugs. Skin reactions due to amitriptyline (a tricyclic antidepressant agent) include rashes and hypersensitivity reactions (for example, urticaria and photosensitivity) as well as hyperpigmentation. Hypersensitivity syndrome is a specific severe idiosyncratic reaction causing skin, liver, joint, and haematological abnormalities, which usually resolve after the discontinuation of the implicated drug. A case of a 24 year old woman who experienced hypersensitivity syndrome three weeks after the initiation of amitriptyline is reported.


Keywords: tricyclic antidepressant drugs; amitriptyline; adverse cutaneous reactions; hypersensitivity syndrome PMID:10824052

  8. [Delayed hypersensitivity to protamine and immediate hypersensitivity to insulin].

    PubMed

    Köllner, A; Senff, H; Engelmann, L; Kalveram, K J; Velcovsky, H G; Haneke, E

    1991-08-16

    A 63-year-old female, with type II diabetes mellitus, diagnosed in 1967, was started on combination therapy with sulphonylureas and human depot insulin in May 1989, because of inadequate blood sugar control with sulphonylureas alone. Within 3 months she began to develop nodular skin reactions at the site of injection, 12-24 hours after insulin injections. Intradermal testing demonstrated delayed (Gell and Coombs type IV) hypersensitivity to protamine. No specific IgE or IgG antibodies were demonstrable. She was changed to protamine-free human delayed action insulin. After an initial reaction-free period, red urticarial lesions, attributable to immediate (Gell and Coombs type I) hypersensitivity to human insulin, appeared at the injection sites. There were no other complications with continued insulin therapy, and after about 6 weeks no further local reactions were detectable. When an allergic reaction to an insulin preparation is suspected, careful immunological investigation should be performed, to ensure adequate treatment without risk to the patient.

  9. 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.

  10. AN OUTBREAK OF HYPERSENSITIVITY PNEUMONITIS AT A METALWORKING PLANT: A LONGITUDINAL ASSESSMENT OF INTERVENTION EFFECTIVENESS. (R825251)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  11. Hypersensitivity reactions to titanium: diagnosis and management.

    PubMed

    Wood, Megan M; Warshaw, Erin M

    2015-01-01

    Titanium is notable for its biocompatibility and is used as biologic implant material across surgical specialties, especially in metal-sensitive individuals. However, rare cases of titanium hypersensitivity reactions are reported in the literature. This article discusses the properties and biological behavior of titanium and provides a thorough review of the literature on reported cases, diagnostic techniques, and approach to management of titanium hypersensitivity.

  12. Management of dentinal hypersensitivity: a review.

    PubMed

    Parolia, Abhishek; Kundabala, M; Mohan, Mandakini

    2011-03-01

    Dentinal hypersensitivity is a very common clinical finding that can cause considerable concern for the patient. Clinicians must understand the various etiological factors, their complexities, and numerous treatment options available. This article reviews the etiology, management, and prevention of dentinal hypersensitivity. PMID:21563596

  13. Hypersensitivity reactions to synthetic haemodialysis membranes.

    PubMed

    Sánchez-Villanueva, Rafael J; González, Elena; Quirce, Santiago; Díaz, Raquel; Alvarez, Laura; Menéndez, David; Rodríguez-Gayo, Lucía; Bajo, M Auxiliadora; Selgas, Rafael

    2014-01-01

    Undergoing a haemodialysis (HD) session poses a certain risk of hypersensitivity adverse reactions as large quantities of blood are in contact with various synthetic materials. Hypersensitivity reactions to ethylene oxide and non-biocompatible membranes, such as cuprophane, have been described in HD. Cases of hypersensitivity with biocompatible membranes, such as polysulfone, and even polysulfone-polyvinylpyrrolidone, have also been reported. In this article we describe six cases of mostly early-stage hypersensitivity reactions to HD occurring in our department, characterised by malaise, desaturation, bronchospasm and arterial hypotension, with good response to the session’s temporary suspension and with reappearance in subsequent sessions that used a synthetic dialyser. No hypersensitivity reactions reappeared in successive observations when the sessions were carried out using a cellulose membrane.

  14. Pain hypersensitivity and spinal nociceptive hypersensitivity in chronic pain: prevalence and associated factors.

    PubMed

    Curatolo, Michele; Müller, Monika; Ashraf, Aroosiah; Neziri, Alban Y; Streitberger, Konrad; Andersen, Ole K; Arendt-Nielsen, Lars

    2015-11-01

    Hypersensitivity of pain pathways is considered a relevant determinant of symptoms in chronic pain patients, but data on its prevalence are very limited. To our knowledge, no data on the prevalence of spinal nociceptive hypersensitivity are available. We studied the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity in 961 consecutive patients with various chronic pain conditions. Pain threshold and nociceptive withdrawal reflex threshold to electrical stimulation were used to assess pain hypersensitivity and spinal nociceptive hypersensitivity, respectively. Using 10th percentile cutoff of previously determined reference values, the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity (95% confidence interval) was 71.2 (68.3-74.0) and 80.0 (77.0-82.6), respectively. As a secondary aim, we analyzed demographic, psychosocial, and clinical characteristics as factors potentially associated with pain hypersensitivity and spinal nociceptive hypersensitivity using logistic regression models. Both hypersensitivity parameters were unaffected by most factors analyzed. Depression, catastrophizing, pain-related sleep interference, and average pain intensity were significantly associated with hypersensitivity. However, none of them was significant for both unadjusted and adjusted analyses. Furthermore, the odds ratios were very low, indicating modest quantitative impact. To our knowledge, this is the largest prevalence study on central hypersensitivity and the first one on the prevalence of spinal nociceptive hypersensitivity in chronic pain patients. The results revealed an impressively high prevalence, supporting a high clinical relevance of this phenomenon. Electrical pain thresholds and nociceptive withdrawal reflex explore aspects of pain processing that are mostly independent of sociodemographic, psychological, and clinical pain-related characteristics.

  15. Radiation pneumonitis after stereotactic radiation therapy for lung cancer

    PubMed Central

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

    2014-01-01

    Stereotactic body radiation therapy (SBRT) has a local control rate of 95% at 2 years for non-small cell lung cancer (NSCLC) and should improve the prognosis of inoperable patients, elderly patients, and patients with significant comorbidities who have early-stage NSCLC. The safety of SBRT is being confirmed in international, multi-institutional Phase II trials for peripheral lung cancer in both inoperable and operable patients, but reports so far have found that SBRT is a safe and effective treatment for early-stage NSCLC and early metastatic lung cancer. Radiation pneumonitis (RP) is one of the most common toxicities of SBRT. Although most post-treatment RP is Grade 1 or 2 and either asymptomatic or manageable, a few cases are severe, symptomatic, and there is a risk for mortality. The reported rates of symptomatic RP after SBRT range from 9% to 28%. Being able to predict the risk of RP after SBRT is extremely useful in treatment planning. A dose-effect relationship has been demonstrated, but suggested dose-volume factors like mean lung dose, lung V20, and/or lung V2.5 differed among the reports. We found that patients who present with an interstitial pneumonitis shadow on computed tomography scan and high levels of serum Krebs von den Lungen-6 and surfactant protein D have a high rate of severe radiation pneumonitis after SBRT. At our institution, lung cancer patients with these risk factors have not received SBRT since 2006, and our rate of severe RP after SBRT has decreased significantly since then. PMID:25276313

  16. Severe hypersensitivity reaction to minocycline.

    PubMed

    de Paz, S; Pérez, A; Gómez, M; Trampal, A; Domínguez Lázaro, A

    1999-01-01

    Minocycline is a tetracycline derivative mainly used in the treatment of acne vulgaris in young persons. Adverse events have been reported with minocycline, although it can be considered a safe drug. We report a case of severe hypersensitivity reaction to minocycline in a young patient. Laboratory examinations, chest X-ray, skin test and skin biopsy were performed. Oral challenge test with minocycline was not carried out as it can be hazardous. A case of severe reaction to minocycline is described in this article. The clinical and laboratory findings may be helpful in diagnosing similar reactions for which the immunological mechanisms are unknown. Moreover, this type of reaction must be recognized early due to the potential fatal outcome.

  17. Hypersensitivity reactions to vaccine components.

    PubMed

    Heidary, Noushin; Cohen, David E

    2005-09-01

    Vaccines are responsible for the control of many infectious diseases that were once common in the United States, including polio, measles, diphtheria, pertussis (whooping cough), rubella (German measles), mumps, tetanus, and Haemophilus influenzae type b. National efforts to generate collaboration between federal, state, and local governments and public and private health care providers have resulted in record high levels of vaccination coverage in the United States. The high rate of US vaccinations is paralleled by growing concerns about the safety of their delivery. The variety of substances used in vaccines sometimes causes the development of cutaneous reactions in susceptible adults and children. This article will review adverse cutaneous events consistent with hypersensitivity reactions to the following ingredients in vaccines: aluminum, thimerosal, 2-phenoxyethanol, formaldehyde, and neomycin.

  18. Testing for Drug Hypersensitivity Syndromes

    PubMed Central

    Rive, Craig M; Bourke, Jack; Phillips, Elizabeth J

    2013-01-01

    Adverse drug reactions are a common cause of patient morbidity and mortality. Type B drug reactions comprise only 20% of all drug reactions but they tend to be primarily immunologically mediated and less dependent on the drug’s pharmacological action and dose. Common Type B reactions seen in clinical practice are those of the immediate, IgE, Gell-Coombs Type I reactions, and the delayed, T-cell mediated, Type IV reactions. Management of these types of reactions, once they have occurred, requires careful consideration and recognition of the utility of routine diagnostic tests followed by ancillary specialised diagnostic testing. For Type I, IgE mediated reactions this includes prick/intradermal skin testing and oral provocation. For Type IV, T-cell mediated reactions this includes a variety of in vivo (patch testing) and ex vivo tests, many of which are currently mainly used in highly specialised research laboratories. The recent association of many serious delayed (Type IV) hypersensitivity reactions to specific drugs with HLA class I and II alleles has created the opportunity for HLA screening to exclude high risk populations from exposure to the implicated drug and hence prevent clinical reactions. For example, the 100% negative predictive value of HLA-B*5701 for true immunologically mediated abacavir hypersensitivity and the development of feasible, inexpensive DNA-based molecular tests has led to incorporation of HLA-B*5701 screening in routine HIV clinical practice. The mechanism by which drugs specifically interact with HLA has been recently characterised and promises to lead to strategies for pre-clinical screening to inform drug development and design. PMID:23592889

  19. Methotrexate-induced pneumonitis in a patient with Crohn's disease.

    PubMed

    Margagnoni, Giovanna; Papi, Valeria; Aratari, Annalisa; Triolo, Luca; Papi, Claudio

    2010-06-01

    Pulmonary toxicity is a well recognised but infrequent adverse event of treatment with methotrexate. The vast majority of cases have occurred in patients with rheumatoid arthritis; here we present the case of a 44-year old woman with ileo-colonic Crohn's disease who developed methotrexate pneumonitis. The patient had a 10 year history of Crohn's disease and, in the last 18 months, she was treated with oral methotrexate because of steroid-dependency and intolerance to thiopurines. She was admitted to the hospital because of acute dyspnoea, non-productive cough and fever. High-resolution CT scan showed diffuse bilateral areas of ground-glass opacity, and pulmonary function tests disclosed a mild obstructive pattern with a decrease in carbon monoxide diffusing capacity. Blood cultures for pathogenic bacteria or fungi were negative as well as serologic tests against major pneumotropic agents. Methotrexate-induced lung injury was considered: the drug was discontinued and the patient received a steroid course with rapid symptomatic improvement. After 4 weeks pulmonary function tests and high-resolution chest CT scan were normal. To our knowledge this is the second reported case of methotrexate-induced pneumonitis occurring in a patient with Crohn's disease. A definite diagnosis has been made not invasively according to clinical, laboratory and radiological criteria and excluding any infectious aetiology of the pulmonary findings. PMID:21122509

  20. 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.

  1. Sympathoinhibition and hypotension in carotid sinus hypersensitivity

    NASA Technical Reports Server (NTRS)

    Smith, M. L.; Ellenbogen, K. A.; Eckberg, D. L.

    1992-01-01

    Carotid sinus reflex hypersensitivity is a known cause of syncope in humans. The condition is characterized by cardioinhibition and vasodepression, each to varying degrees. The extent and importance of sympathoinhibition has not been determined in patients with carotid sinus hypersensitivity. This study reports on the extent of sympathoinhibition measured directly directly during carotid massage with and without atrioventricular sequential pacing, in a patient with symptomatic carotid sinus reflex hypersensitivity. Carotid massage elicited asystole, hypotension and complete inhibition of muscle sympathetic nerve activity. Carotid massage during atrioventricular pacing produced similar sympathoinhibition, but with minimal hypotension. Therefore, sympathoinhibition did not contribute importantly to the hypotension during carotid massage in the supine position in this patient. Further investigations are required to elucidate the relation of sympathoinhibition to hypotension in patients with carotid sinus hypersensitivity in the upright position.

  2. Food hypersensitivity to lamb in a cat.

    PubMed

    Reedy, L M

    1994-04-01

    Severe facial pruritus in a cat was caused by food hypersensitivity to lamb. The cat had been fed an exclusive diet of lamb for 2 years after it had been diagnosed to have food hypersensitivity to fish. Signs, including erythema, alopecia, and excoriations of the head and neck, were poorly responsive to corticosteroid administration, but resolved within a few weeks after removal of the suspected allergen.

  3. Drug-Hypersensitivity Syndrome: Diagnosis and Treatment

    PubMed Central

    Hamm, Rose L.

    2012-01-01

    Drug-induced hypersensitivity syndrome is a systemic autoimmune disorder that results in mucocutaneous symptoms ranging in severity from mild pruritus to life-threatening skin and mucosal loss, with different nomenclature depending on the severity of the symptoms. The purpose of this article is to review the recent advances in understanding the pathology of drug-induced hypersensitivity syndrome, as well as current recommendations for both medical and wound management. PMID:24527369

  4. Benign nasopharyngeal lymphoid tumors, lymphoepithelial lesions, and lymphocytic interstitial pneumonitis.

    PubMed

    Puterman, M; Fliss, D M; Goldstein, J; Zirkin, H

    1988-09-01

    A clinico-pathologic and immunologic case study of a 57-year-old woman who has shown progressive lymphoid proliferations and lymphocyte dysfunction over the course of 10 years is presented. Early in the course of her disease, she presented with recurrent benign nasopharyngeal lymphoid tumors. She subsequently developed benign lymphoepithelial lesions involving both a submandibular and then a parotid salivary gland. She eventually underwent pneumonectomy for lymphocytic interstitial pneumonitis with marked cystic degeneration and lung destruction. Although frank malignancy has not been demonstrated review of her nasopharyngeal biopsies and of her pulmonary pathology shows a tendency toward distinct cellular uniformity with loss of follicles and germinal centers. Concurrently, immunologic studies have demonstrated abnormalities of cell mediated (T cell) function.

  5. Renin-Angiotensin System Suppression Mitigates Experimental Radiation Pneumonitis

    SciTech Connect

    Ghosh, Swarajit N.; Zhang Rong; Fish, Brian L.; Semenenko, Vladimir A.; Li, X. Allen; Moulder, John E.; Jacobs, Elizabeth R.; Medhora, Meetha

    2009-12-01

    Purpose: To find the mitigators of pneumonitis induced by moderate doses of thoracic radiation (10-15 Gy). Methods and Materials: Unanesthetized WAG/RijCmcr female rats received a single dose of X-irradiation (10, 12, or 15 Gy at 1.615 Gy/min) to the thorax. Captopril (an angiotensin-converting enzyme inhibitor) or losartan (an angiotensin receptor blocker) was administered in the drinking water after irradiation. Pulmonary structure and function were assessed after 8 weeks in randomly selected rats by evaluating the breathing rate, ex vivo vascular reactivity, and histopathologic findings. Survival analysis was undertaken on all animals, except those scheduled for death. Results: Survival after a dose of 10 Gy to the thorax was not different from that of unirradiated rats for <=1 year. Survival decreased to <50% by 45 weeks after 12 Gy and by 8-9 weeks after 15 Gy. Captopril (17-56mg/kg/d) improved survival and reduced radiation-induced increases in breathing rate, changes in vascular reactivity, and histopathologic evidence of injury. Radiation-induced increases in the breathing rate were prevented even if captopril was started 1 week after irradiation or if it was discontinued after 5 weeks. Losartan, although effective in reducing mortality, was not as efficacious as captopril in mitigating radiation-induced increases in the breathing rate or altered vasoreactivity. Conclusion: In rats, a moderate thoracic radiation dose induced pneumonitis and morbidity. These injuries were mitigated by captopril even when it was begun 1 week after radiation or if discontinued 5 weeks after exposure. Losartan was less effective in protecting against radiation-induced changes in vascular reactivity or tachypnea.

  6. Renin-Angiotensin System Suppression Mitigates Experimental Radiation Pneumonitis

    PubMed Central

    Ghosh, Swarajit N.; Zhang, Rong; Fish, Brian L.; Semenenko, Vladimir A.; Li, X. Allen; Moulder, John E.; Jacobs, Elizabeth R.; Medhora, Meetha

    2009-01-01

    Purpose To find mitigators of pneumonitis induced by moderate doses of thoracic radiation (10–15 Gy). Materials and Methods Unanesthetized WAG/RijCmcr female rats received single doses of X-irradiation (10, 12 or 15 Gy at 1.615 Gy/minute) to the thorax. Captopril (an angiotensin converting enzyme inhibitor) or losartan (an angiotensin receptor blocker) was administered in drinking water after irradiation. Pulmonary structure and function were assessed after 8 weeks in randomly selected rats by evaluating breathing rate, ex vivo vascular reactivity and histopathology. Survival analysis was undertaken on all animals except those scheduled for sacrifice. Results Survival following a dose of 10 Gy to the thorax was not different from unirradiated rats up to one year. Survival decreased to less than 50%, by 45 weeks after 12 Gy and by 8–9 weeks after 15 Gy. Captopril (17–56 mg/kg/day) improved survival and reduced radiation-induced increases in breathing rate, changes in vascular reactivity and histopathological evidence of injury. Radiation-induced increases in breathing rate were prevented even if captopril was started 1 week following irradiation or if it was discontinued after 5 weeks. Losartan, though effective in reducing mortality was not as efficacious as captopril in mitigating radiation-induced increases in breathing rate or altered vasoreactivity. Conclusions In rats, a moderate thoracic dose of radiation induced pneumonitis and morbidity. These injuries were mitigated by captopril even when it was commenced 1 week after irradiation or if discontinued after 5 weeks following exposure. Losartan was less effective in protecting against radiation-induced changes in vascular reactivity or tachypnea. PMID:19931735

  7. 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

  8. Hypersensitivity reactions associated with oxaliplatin.

    PubMed

    Saif, M Wasif

    2006-09-01

    The reported incidence of hypersensitivity reactions (HSRs) associated with oxaliplatin in patients with colorectal cancer (CRC) is approximately 12%, with 1 - 2% of patients developing grade 3 or 4 in severity. However, the recent rising incidence of HSR to oxaliplatin observed is the result of increasing clinical use. HSR to oxaliplatin may manifest as facial flushing, rash/hives, tachycardia, dyspnoea, erythema, pruritus, fever, tongue swelling, headache, chills, weakness, vomiting, burning sensations, dizziness and oedema. Anaphylactic shock is rare but serious, and must be considered in the event of hypotension. No definitive approaches to prevent and treat HSR associated with oxaliplatin are available; however, few successful strategies have been reported. Such strategies include: slowing the infusion rate, use of steroids and antagonists of type 1 and 2 histamine receptors, and desensitisation. Successful implementation of oxaliplatin desensitisation protocols based on other platinum-containing compounds have been reported, which could enable a small number of patients who experience severe HSR to further receive an effective therapy for CRC. However, reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitisation strategies are still missing. Recently, subcutaneous adrenaline has also been utilised as an alternative approach to manage HSR to oxaliplatin. Knowledge of this rare but real toxicity of oxaliplatin is paramount because the use of this drug continues to increase not only for the treatment of patients with stage II-IV CRC, but also other solid malignancies. In this article, the author discusses the incidence, clinical presentation, pathogenesis, risk factors and current strategies of management of HSR associated with oxaliplatin. PMID:16907658

  9. Serum IgG response in calves to the putative pneumonic virulence factor Gs60 of Mannheimia haemolytica A1.

    PubMed

    Orouji, Shahriar; Hodgins, Douglas C; Lo, Reggie Y C; Shewen, Patricia E

    2012-10-01

    Bovine pneumonic pasteurellosis vaccines incorporate various antigens of Mannheimia haemolytica, including the acknowledged virulence factor leukotoxin (Lkt), and Gs60, a surface lipoprotein. To examine the role of antibodies to Gs60 in protection, an enzyme-linked immunosorbent assay (ELISA) was developed for retrospective analysis of serum samples from previous trials in which vaccines containing native or recombinant Gs60 were administered parenterally. The analysis revealed a positive correlation between the titer of antibodies to Gs60 and protection against experimental challenge in both vaccinates and naturally exposed controls. There was a strong correlation between production of IgG antibodies to Gs60 and Lkt neutralizing antibodies. Analysis of the relationship between the serum antibody titers and resistance to experimental challenge using linear statistical models revealed a significant association between prechallenge titers of serum antibodies to Lkt and protection. Further analysis suggested that antibodies against Gs60 were beneficial when Lkt neutralizing antibody titers were low.

  10. 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.

  11. 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.

  12. Hypersensitivity to hypercapnia: definition/(s).

    PubMed

    Vickers, Kristin

    2012-05-15

    Empirical evidence indicates that panic disorder (PD) patients experience hypersensitivity to hypercapnia, a condition in which the blood level of carbon dioxide exceeds the normal value. The importance of this research line is substantial and indeed, hypercapnic hypersensitivity has been advanced as a possible endophenotype of panic. Definitions of "hypersensitivity," however, have varied. The purpose of this brief review is to delineate and critique different definitions of hypercapnic hypersensitivity. Several definitions - panic attack rate, panic symptoms including dyspnea, subjective anxiety, and respiratory disturbance - are explored. The review concludes that although no ideal definition has emerged, marked anxiety post-hypercapnia has substantial support as a putative trait marker of PD. The term "subjective hypersensitivity" (Coryell et al., 2001) is re-introduced to denote pronounced anxiety post-hypercapnia and recommended for use along with its previous definition: increased self-reported anxiety measured on a continuous visual analog scale, already widely in use. Due to the well-established link between panic and respiration, definitional candidates focusing on aberrant respiratory response - less investigated as trait markers of PD in high risk studies - warrant scrutiny as well. Several reasons why definitional clarity might be beneficial are presented, along with ideas for future research.

  13. Power toothbrushes, gender, and dentin hypersensitivity.

    PubMed

    Hefti, A F; Stone, C

    2000-06-01

    Power toothbrushes require less force for plaque removal than manual brushes. In addition, in vitro studies have indicated that brushing with low force could occlude patent dentin tubules by formation of a smear layer. Hence, lessening the force necessary to remove plaque may reduce dentin hypersensitivity. However, it was recently suggested that the use of an oscillating/rotating power toothbrush could decrease tooth sensitivity as compared to a sonic power toothbrush. Therefore, the objective of the present research was to compare the effect on dentin hypersensitivity of two different types of power brushes, the Optiva Sonicare and the Braun Oral B Ultra Plaque Remover. The null hypothesis was tested in an 8-week, randomized, parallel group, examiner-blind clinical trial. Fifty-nine subjects with a history of dentin hypersensitivity participated. Dentin hypersensitivity-associated pain was elicited using tactile and evaporative stimuli and assessed using a visual analog scale (VAS) instrument. Clinical examinations were carried out at screening and baseline and repeated after 8 weeks of twice daily use of the power brushes. Data analysis was performed on VAS scores obtained at the final visit following adjustment for group differences at baseline. A 35% to 40% reduction in pain as compared to baseline was observed in both treatment groups. Treatment-related differences were not statistically significant. A gender-related effect on dentin hypersensitivity was observed using the tactile stimulus and may merit further investigation.

  14. Glucocorticoid hypersensitivity syndrome--a case report.

    PubMed

    Krysiak, R; Okopien, B

    2012-11-01

    Glucocorticoid hypersensitivity syndrome has been reported to date only in several patients. This article describes a unique case of this syndrome in a 24-year old female admitted to hospital because of arterial hypertension and obesity. Although her clinical picture suggested Cushing's syndrome, she had low adrenocorticotropic hormone (ACTH) and cortisol levels with a poor response to corticotrophin-releasing hormone and Synacthen. In turn, an overnight dexamethasone suppression test with 0.25 mg of dexamethasone led to a dramatic decrease in morning cortisol. A diagnosis of glucocorticoid hypersensitivity was made and the patient started treatment with ketoconazole and cabergoline, which resulted in some clinical improvement. This case illustrates the need for clinical awareness of glucocorticoid hypersensitivity in patients suspected of Cushing's syndrome.

  15. TRPA1 Contributes to Cold Hypersensitivity

    PubMed Central

    Camino, Donato del; Murphy, Sarah; Heiry, Melissa; Barrett, Lee B.; Earley, Taryn J.; Cook, Colby A.; Petrus, Matt J.; Zhao, Michael; D'Amours, Marc; Deering, Nate; Brenner, Gary J.; Costigan, Michael; Hayward, Neil J.; Chong, Jayhong A.; Fanger, Christopher M.; Woolf, Clifford J.; Patapoutian, Ardem; Moran, Magdalene M.

    2010-01-01

    TRPA1 is a non-selective cation channel expressed by nociceptors. While it is widely accepted that TRPA1 serves as a broad irritancy receptor for a variety of reactive chemicals, its role in cold sensation remains controversial. Here, we demonstrate that mild cooling markedly increases agonist-evoked rat TRPA1 currents. In the absence of an agonist, even noxious cold only increases current amplitude slightly. These results suggest that TRPA1 is a key mediator of cold hypersensitivity in pathological conditions where reactive oxygen species and pro-inflammatory activators of the channel are present, but likely plays a comparatively minor role in acute cold sensation. Supporting this, cold hypersensitivity can be induced in wild-type but not Trpa1-/- mice by subcutaneous administration of a TRPA1 agonist. Furthermore, the selective TRPA1 antagonist HC-030031 reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain. PMID:21068322

  16. Interleukin (IL)-1A and IL-6: Applications to the predictive diagnostic testing of radiation pneumonitis

    SciTech Connect

    Chen Yuhchyau . E-mail: yuhchyau_chen@urmc.rochester.edu; Hyrien, Ollivier; Williams, Jacqueline; Okunieff, Paul; Smudzin, Therese; Rubin, Philip

    2005-05-01

    Purpose: To explore the application of interleukin (IL)-1{alpha} and IL-6 measurements in the predictive diagnostic testing for symptomatic radiation pneumonitis (RP). Methods and materials: In a prospective protocol investigating RP and cytokines, IL-1{alpha} and IL-6 values were analyzed by enzyme-linked immunosorbent assay from serial weekly blood samples of patients receiving chest radiation. We analyzed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) over selected threshold values for both cytokines in the application to diagnostic testing. Results: The average coefficient of variation was 51% of the weekly mean IL-1{alpha} level and 39% of the weekly mean IL-6 value. Interleukin 1{alpha} and IL-6 became positively correlated with time. Specificity for both cytokines was better than sensitivity. IL-6 globally outperformed IL-1{alpha} in predicting RP, with higher PPV and NPV. Conclusions: Our data demonstrate the feasibility of applying IL-1{alpha} and IL-6 measurements of blood specimens to predict RP. Interleukin-6 measurements offer stronger positive predictive value than IL-1{alpha}. This application might be further explored in a larger sample of patients.

  17. How to manage asparaginase hypersensitivity in acute lymphoblastic leukemia.

    PubMed

    Burke, Michael J

    2014-12-01

    Outcomes for children with acute lymphoblastic leukemia (ALL) have improved significantly in recent decades, primarily due to dose-intensified, multi-agent chemotherapy regimens, of which asparaginase has played a prominent role. Despite this success, hypersensitivity remains a significant problem, often requiring the termination of asparaginase. Failure to complete the entire asparaginase therapy course due to clinical hypersensitivity, subclinical hypersensitivity (i.e., silent inactivation), or other treatment-related toxicity is associated with poor ALL outcomes. Thus, it is critical to rapidly identify patients who develop clinical/subclinical hypersensitivity and switch these patients to an alternate asparaginase formulation. This article provides an overview of asparaginase hypersensitivity, identification and management of hypersensitivity and subclinical hypersensitivity, and issues related to switching patients to asparaginase Erwinia chrysanthemi following hypersensitivity reaction.

  18. 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

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

    PubMed

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

    2015-09-01

    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.

  20. 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.

  1. 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

  2. Immediate-type hypersensitivity drug reactions

    PubMed Central

    Stone, Shelley F; Phillips, Elizabeth J; Wiese, Michael D; Heddle, Robert J; Brown, Simon G A

    2014-01-01

    Hypersensitivity reactions including anaphylaxis have been reported for nearly all classes of therapeutic reagents and these reactions can occur within minutes to hours of exposure. These reactions are unpredictable, not directly related to dose or the pharmacological action of the drug and have a relatively high mortality risk. This review will focus on the clinical presentation, immune mechanisms, diagnosis and prevention of the most serious form of immediate onset drug hypersensitivity reaction, anaphylaxis. The incidence of drug-induced anaphylaxis deaths appears to be increasing and our understanding of the multiple and complex reasons for the unpredictable nature of anaphylaxis to drugs is also expanding. This review highlights the importance of enhancing our understanding of the biology of the patient (i.e. immune response, genetics) as well as the pharmacology and chemistry of the drug when investigating, diagnosing and treating drug hypersensitivity. Misdiagnosis of drug hypersensitivity leads to substantial patient risk and cost. Although oral provocation is often considered the gold standard of diagnosis, it can pose a potential risk to the patient. There is an urgent need to improve and standardize diagnostic testing and desensitization protocols as other diagnostic tests currently available for assessment of immediate drug allergy are not highly predictive. PMID:24286446

  3. Severe Hyperacusis, Photophobia, and Skin Hypersensitivity

    PubMed Central

    Fioretti, Alessandra Barbara; Varakliotis, Theodoros; Poli, Otello; Cantagallo, Manuela; Eibenstein, Alberto

    2016-01-01

    We report a case of a patient with severe hyperacusis, photophobia, and skin hypersensitivity. The patient was initially treated with sound therapy and medical therapy for 4 months and successfully with a selective serotonin reuptake inhibitor (SSRI) and cognitive behavioral therapy which improved her mood and the tolerance for sounds and light. PMID:26981300

  4. 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.

  5. Treatments for hypersensitive noncarious cervical lesions

    PubMed Central

    Veitz-Keenan, Analia; Barna, Julie Ann; Strober, Brad; Matthews, Abigail G.; Collie, Damon; Vena, Donald; Curro, Frederick A.; Thompson, Van P.

    2014-01-01

    Background The Practitioners Engaged in Applied Research and Learning (PEARL) Network conducted a three-armed randomized clinical study to determine the comparative effectiveness of three treatments for hypersensitive noncarious cervical lesions (NCCLs): use of a potassium nitrate dentifrice for treatment of hypersensitivity, placement of a resin-based composite restoration and placement of a sealant. Methods Seventeen trained practitioner-investigators (P-Is) in the PEARL Network enrolled participants (N = 304) with hypersensitive posterior NCCLs who met enrollment criteria. Participants were assigned to treatments randomly. Evaluations were conducted at baseline and at one, three and six months thereafter. Primary outcomes were the reduction or elimination of hypersensitivity as measured clinically and by means of patient-reported outcomes. Results Lesion depth and pretreatment sensitivity (mean, 5.3 on a 0- to 10-point scale) were balanced across treatments, as was sleep bruxism (present in 42.2 percent of participants). The six-month participant recall rate was 99 percent. Treatments significantly reduced mean sensitivity (P < .01), with the sealant and restoration groups displaying a significantly higher reduction (P < .01) than did the dentifrice group. The dentifrice group’s mean (standard deviation) sensitivity at six months was 2.1 (2.1); those of the sealant and restoration groups were 1.0 (1.6) and 0.8 (1.4), respectively. Patient-reported sensitivity (to cold being most pronounced) paralleled clinical measurements at each evaluation. Conclusions Sealing and restoration treatments were effective overall in reducing NCCL hypersensitivity. The potassium nitrate dentifrice reduced sensitivity with increasing effectiveness through six months but not to the degree offered by the other treatments. Practical Implications Sealant or restoration placement is an effective method of immediately reducing NCCL sensitivity. Although a potassium nitrate dentifrice

  6. Anti-PD-1 Inhibitor-Related Pneumonitis in Non-Small Cell Lung Cancer.

    PubMed

    Nishino, Mizuki; Chambers, Emily S; Chong, Curtis R; Ramaiya, Nikhil H; Gray, Stacy W; Marcoux, J Paul; Hatabu, Hiroto; Jänne, Pasi A; Hodi, F Stephen; Awad, Mark M

    2016-04-01

    The recent approval of two PD-1 inhibitors for the treatment of non-small cell lung cancer (NSCLC) has rapidly led to the widespread use of these agents in oncology practices. Pneumonitis has been recognized as a potentially life-threatening adverse event among NSCLC patients treated with PD-1 inhibitors; however, the detailed clinical and radiographic manifestations of this entity remain to be described. We report on two cases of anti-PD-1 pneumonitis in advanced NSCLC patients treated with nivolumab after its FDA approval. Both patients presented with ground-glass and reticular opacities and consolidations in a peripheral distribution on CT, demonstrating a radiographic pattern of cryptogenic organizing pneumonia. Consolidations were extensive and rapidly developed within 8 weeks of therapy in both cases. Both patients were treated with corticosteroids with subsequent improvement of respiratory symptoms and radiographic findings. One patient experienced recurrent pneumonitis after completing corticosteroid taper, or a "pneumonitis flare," in the absence of nivolumab retreatment, with subsequent improvement upon corticosteroid readministration. With the increasing use of immune checkpoint inhibitors in a growing number of tumor types, awareness of the radiographic and clinical manifestations of PD-1 inhibitor-related pneumonitis will be critical for the prompt diagnosis and management of this potentially serious adverse event. PMID:26865455

  7. Effect of oil composition on both adjuvant-induced arthritis and delayed hypersensitivity to purified protein derivative and peptidoglycans in various rat strains.

    PubMed Central

    Kohashi, O; Pearson, M; Beck, F J; Alexander, M

    1977-01-01

    We confirmed that, when immunized with a conventional complete Freund adjuvant (water in oil), Lewis rats were highly susceptible to adjuvant arthritis, Fisher rats were less susceptible, and Buffalo rats were much less susceptible. However, mycobacterial delipidated cells in squalane (squalane-type adjuvant) produced severe arthritis with almost 100% incidence even in the less susceptible rat strains except for Buffalo rats. With regard to an immune response, Freund complete adjuvant induced strong delayed hypersensitivity to purified protein derivative (PPD) and peptidoglycan (PG) in all rat strains used, Whereas the squalane-type adjuvant induced these hypersensitivities only in Lewis and Buffalo rats, but not in Fisher and Brown Norway rats. No correlation was found between development of arthritis and delayed hypersensitivity to either PPD or PG, or both. It seems that PPD hypersensitivity may be inherited differently from PG hypersensitivity. PMID:892904

  8. Effect of oil composition on both adjuvant-induced arthritis and delayed hypersensitivity to purified protein derivative and peptidoglycans in various rat strains.

    PubMed

    Kohashi, O; Pearson, M; Beck, F J; Alexander, M

    1977-08-01

    We confirmed that, when immunized with a conventional complete Freund adjuvant (water in oil), Lewis rats were highly susceptible to adjuvant arthritis, Fisher rats were less susceptible, and Buffalo rats were much less susceptible. However, mycobacterial delipidated cells in squalane (squalane-type adjuvant) produced severe arthritis with almost 100% incidence even in the less susceptible rat strains except for Buffalo rats. With regard to an immune response, Freund complete adjuvant induced strong delayed hypersensitivity to purified protein derivative (PPD) and peptidoglycan (PG) in all rat strains used, Whereas the squalane-type adjuvant induced these hypersensitivities only in Lewis and Buffalo rats, but not in Fisher and Brown Norway rats. No correlation was found between development of arthritis and delayed hypersensitivity to either PPD or PG, or both. It seems that PPD hypersensitivity may be inherited differently from PG hypersensitivity.

  9. HLA-A★3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans

    PubMed Central

    McCormack, Mark; Alfirevic, Ana; Bourgeois, Stephane; Farrell, John J.; Kasperavičiūtė, Dalia; Carrington, Mary; Sills, Graeme J.; Marson, Tony; Jia, Xiaoming; de Bakker, Paul I.W.; Chinthapalli, Krishna; Molokhia, Mariam; Johnson, Michael R.; O’Connor, Gerard D.; Chaila, Elijah; Alhusaini, Saud; Shianna, Kevin V.; Radtke, Rodney A.; Heinzen, Erin L.; Walley, Nicole; Pandolfo, Massimo; Pichler, Werner; Park, B. Kevin; Depondt, Chantal; Sisodiya, Sanjay M.; Goldstein, David B.; Deloukas, Panos; Delanty, Norman; Cavalleri, Gianpiero L.; Pirmohamed, Munir

    2011-01-01

    BACKGROUND Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B★1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS–TEN) in the Han Chinese and other Asian populations but not in European populations. METHODS We performed a genomewide association study of samples obtained from 22 subjects with carbamazepine-induced hypersensitivity syndrome, 43 subjects with carbamazepine-induced maculopapular exanthema, and 3987 control subjects, all of European descent. We tested for an association between disease and HLA alleles through proxy single-nucleotide polymorphisms and imputation, confirming associations by high-resolution sequence-based HLA typing. We replicated the associations in samples from 145 subjects with carbamazepine-induced hypersensitivity reactions. RESULTS The HLA-A★3101 allele, which has a prevalence of 2 to 5% in Northern European populations, was significantly associated with the hypersensitivity syndrome (P = 3.5×10−8). An independent genomewide association study of samples from subjects with maculopapular exanthema also showed an association with the HLA-A★3101 allele (P = 1.1×10−6). Follow-up genotyping confirmed the variant as a risk factor for the hypersensitivity syndrome (odds ratio, 12.41; 95% confidence interval [CI], 1.27 to 121.03), maculopapular exanthema (odds ratio, 8.33; 95% CI, 3.59 to 19.36), and SJS–TEN (odds ratio, 25.93; 95% CI, 4.93 to 116.18). CONCLUSIONS The presence of the HLA-A★3101 allele was associated with carbamazepine-induced hypersensitivity reactions among subjects of Northern European ancestry. The presence of the allele increased the risk from 5.0% to 26.0%, whereas its absence reduced the risk from 5.0% to 3.8%. (Funded by the U.K. Department of Health and others.) PMID:21428769

  10. Cutaneous hypersensitivity responses to Rhipicephalus tick larval antigens in pre-sensitized cattle.

    PubMed

    Marufu, M C; Chimonyo, M; Mans, B J; Dzama, K

    2013-06-01

    Nguni cattle are known to be more resistant to ticks than Bonsmara cattle, even if the immunological mechanisms responsible for this phenomenon are not fully understood. Cutaneous hypersensitivity responses to unfed larval extracts (ULE) of the ticks Rhipicephalus decoloratus and Rhipicephalus microplus were investigated in Nguni and Bonsmara cattle to improve knowledge on the immunity to ticks. Hypersensitivity reactions were induced by intradermal inoculation of 0.1ml of ULE of R. decoloratus and R. microplus ticks (50μg protein) in the right and left ear, respectively, of 8-9-month-old Nguni (n=11) and Bonsmara (n=9) heifers. Ear thickness was measured using callipers before and 0.5, 1, 6, 24, 48, and 72h post inoculation (PI). Bonsmara cattle showed a more intense immediate reaction with maximum response at 1h PI and no delayed hypersensitivity reaction. Nguni heifers, conversely, presented a less intense immediate reaction with maximum response at 1h PI, and a delayed hypersensitivity reaction at 72h PI. Reactions to R. decoloratus ULE produced a more intense skin response than to R. microplus in both breeds at all time intervals. Nguni cattle showed lower tick infestation indicating higher tick resistance than Bonsmara cattle. Delayed hypersensitivity reaction could be associated with superior tick resistance in the Nguni breed, while immediate hypersensitivity reaction could be associated with increased tick susceptibility in the Bonsmara breed. This study indicates the need for further investigations on the correlation of tick resistance and cellular immune responses to tick infestation in Nguni cattle. PMID:23453577

  11. Altered colorectal afferent function associated with TNBS-induced visceral hypersensitivity in mice.

    PubMed

    Feng, Bin; La, Jun-Ho; Tanaka, Takahiro; Schwartz, Erica S; McMurray, Timothy P; Gebhart, G F

    2012-10-01

    Inflammation of the distal bowel is often associated with abdominal pain and hypersensitivity, but whether and which colorectal afferents contribute to the hypersensitivity is unknown. Using a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, we investigated colorectal hypersensitivity following intracolonic TNBS and associated changes in colorectum and afferent functions. C57BL/6 mice were treated intracolonically with TNBS or saline. Visceromotor responses to colorectal distension (15-60 mmHg) were recorded over 8 wk in TNBS- and saline-treated (control) mice. In other mice treated with TNBS or saline, colorectal inflammation was assessed by myeloperoxidase assay and immunohistological staining. In vitro single-fiber recordings were conducted on both TNBS and saline-treated mice to assess colorectal afferent function. Mice exhibited significant colorectal hypersensitivity through day 14 after TNBS treatment that resolved by day 28 with no resensitization through day 56. TNBS induced a neutrophil- and macrophage-based colorectal inflammation as well as loss of nerve fibers, all of which resolved by days 14-28. Single-fiber recordings revealed a net increase in afferent drive from stretch-sensitive colorectal afferents at day 14 post-TNBS and reduced proportions of mechanically insensitive afferents (MIAs) at days 14-28. Intracolonic TNBS-induced colorectal inflammation was associated with the development and recovery of hypersensitivity in mice, which correlated with a transient increase and recovery of sensitization of stretch-sensitive colorectal afferents and MIAs. These results indicate that the development and maintenance of colorectal hypersensitivity following inflammation are mediated by peripheral drive from stretch-sensitive colorectal afferents and a potential contribution from MIAs.

  12. Altered colorectal afferent function associated with TNBS-induced visceral hypersensitivity in mice

    PubMed Central

    La, Jun-Ho; Tanaka, Takahiro; Schwartz, Erica S.; McMurray, Timothy P.; Gebhart, G. F.

    2012-01-01

    Inflammation of the distal bowel is often associated with abdominal pain and hypersensitivity, but whether and which colorectal afferents contribute to the hypersensitivity is unknown. Using a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, we investigated colorectal hypersensitivity following intracolonic TNBS and associated changes in colorectum and afferent functions. C57BL/6 mice were treated intracolonically with TNBS or saline. Visceromotor responses to colorectal distension (15–60 mmHg) were recorded over 8 wk in TNBS- and saline-treated (control) mice. In other mice treated with TNBS or saline, colorectal inflammation was assessed by myeloperoxidase assay and immunohistological staining. In vitro single-fiber recordings were conducted on both TNBS and saline-treated mice to assess colorectal afferent function. Mice exhibited significant colorectal hypersensitivity through day 14 after TNBS treatment that resolved by day 28 with no resensitization through day 56. TNBS induced a neutrophil- and macrophage-based colorectal inflammation as well as loss of nerve fibers, all of which resolved by days 14–28. Single-fiber recordings revealed a net increase in afferent drive from stretch-sensitive colorectal afferents at day 14 post-TNBS and reduced proportions of mechanically insensitive afferents (MIAs) at days 14–28. Intracolonic TNBS-induced colorectal inflammation was associated with the development and recovery of hypersensitivity in mice, which correlated with a transient increase and recovery of sensitization of stretch-sensitive colorectal afferents and MIAs. These results indicate that the development and maintenance of colorectal hypersensitivity following inflammation are mediated by peripheral drive from stretch-sensitive colorectal afferents and a potential contribution from MIAs. PMID:22859364

  13. Prospective assessment of dosimetric/physiologic-based models for predicting radiation pneumonitis

    SciTech Connect

    Kocak, Zafer; Borst, Gerben R.; Zeng Jing; Zhou Sumin; Hollis, Donna R.; Zhang Junan; Evans, Elizabeth S.; Folz, Rodney J.; Wong, Terrence; Kahn, Daniel; Belderbos, Jose S.A.; Lebesque, Joos V.; Marks, Lawrence B. . E-mail: marks@radonc.duke.edu

    2007-01-01

    Purpose: Clinical and 3D dosimetric parameters are associated with symptomatic radiation pneumonitis rates in retrospective studies. Such parameters include: mean lung dose (MLD), radiation (RT) dose to perfused lung (via SPECT), and pre-RT lung function. Based on prior publications, we defined pre-RT criteria hypothesized to be predictive for later development of pneumonitis. We herein prospectively test the predictive abilities of these dosimetric/functional parameters on 2 cohorts of patients from Duke and Netherlands Cancer Institute (NKI). Methods and Materials: For the Duke cohort, 55 eligible patients treated between 1999 and 2005 on a prospective IRB-approved study to monitor RT-induced lung injury were analyzed. A similar group of patients treated at the NKI between 1996 and 2002 were identified. Patients believed to be at high and low risk for pneumonitis were defined based on: (1) MLD; (2) OpRP (sum of predicted perfusion reduction based on regional dose-response curve); and (3) pre-RT DLCO. All doses reflected tissue density heterogeneity. The rates of grade {>=}2 pneumonitis in the 'presumed' high and low risk groups were compared using Fisher's exact test. Results: In the Duke group, pneumonitis rates in patients prospectively deemed to be at 'high' vs. 'low' risk are 7 of 20 and 9 of 35, respectively; p = 0.33 one-tailed Fisher's. Similarly, comparable rates for the NKI group are 4 of 21 and 6 of 44, respectively, p = 0.41 one-tailed Fisher's. Conclusion: The prospective model appears unable to accurately segregate patients into high vs. low risk groups. However, considered retrospectively, these data are consistent with prior studies suggesting that dosimetric (e.g., MLD) and functional (e.g., PFTs or SPECT) parameters are predictive for RT-induced pneumonitis. Additional work is needed to better identify, and prospectively assess, predictors of RT-induced lung injury.

  14. 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.

  15. An unexpected positive hypersensitive reaction to eugenol.

    PubMed

    Tammannavar, Praveen; Pushpalatha, C; Jain, Shrenik; Sowmya, S V

    2013-09-18

    Eugenol is an active, principal aromatic liquid responsible for several pharmacological activities. It is widely used in dental practice to relieve pain arising from various sources, such as pulpitis and dentinal hypersensitivity. As a primary irritant and sensitiser, it is known to cause contact urticaria as well as chronic urticaria. However, eugenol causes allergic contact dermatitis, possibly because it can react directly with proteins to form conjugate and reactive haptens. It is found that eugenol in various dental preparations-especially in the case of some zinc oxide-contains preparations such as periodontal dressings and root canal cements. This can cause hypersensitivity when it comes in contact with gingiva or teeth. This article presents a case of immediate allergic contact urticaria to eugenol during dental treatment.

  16. Hypersensitivity vasculitis associated with leuprolide (Lupron).

    PubMed

    Gnanaraj, Joseph; Saif, Muhammad Wasif

    2010-09-01

    Leuprolide (Lupron) is a synthetic analog of naturally occurring gonadotropin-releasing hormone (GnRH). Leuprolide is used as a hormonal antagonist in the treatment of advanced prostatic cancer, and as hormonal therapy in the treatment of endometriosis. Off-label, it is also used in premenopausal or perimenopausal women with hormone-responsive breast cancer for the purpose of ovarian ablation. Ever since its FDA approval in 1985, many adverse reactions have been reported in association with leuprolide ranging from local skin irritation to severe anaphylactoid reactions. In this case report, we present a case of hypersensitivity vasculitis (serum sickness) in a patient who received leuprolide for his prostate cancer. Serum sickness has never been reported as a side-effect of leuprolide. Our case is the first case of serum sickness associated with leuprolide. We emphasize that physicians using leuprolide should be wary of signs and symptoms of hypersensitivity vasculitis or serum sickness.

  17. An unexpected positive hypersensitive reaction to eugenol

    PubMed Central

    Tammannavar, Praveen; C, Pushpalatha; Jain, Shrenik; SV, Sowmya

    2013-01-01

    Eugenol is an active, principal aromatic liquid responsible for several pharmacological activities. It is widely used in dental practice to relieve pain arising from various sources, such as pulpitis and dentinal hypersensitivity. As a primary irritant and sensitiser, it is known to cause contact urticaria as well as chronic urticaria. However, eugenol causes allergic contact dermatitis, possibly because it can react directly with proteins to form conjugate and reactive haptens. It is found that eugenol in various dental preparations-especially in the case of some zinc oxide–contains preparations such as periodontal dressings and root canal cements. This can cause hypersensitivity when it comes in contact with gingiva or teeth. This article presents a case of immediate allergic contact urticaria to eugenol during dental treatment. PMID:24049087

  18. Case of immediate hypersensitivity to beer.

    PubMed

    Inoue, Tomoko; Yagami, Akiko; Shimojo, Naoshi; Hara, Kazuhiro; Nakamura, Masashi; Matsunaga, Kayoko

    2016-06-01

    We report here a case of immediate hypersensitivity to beer, in which a female patient developed angioedema of the eyelids shortly after consuming beer. In skin prick tests, the patient showed positive reactions to the base ingredients of beer, particularly malt and barley. The specific serum immunoglobulin E antibodies against barley and malt displayed weakly positive reactivity. To identify the immunoreactive antigens, malt and barley proteins were separated by 2-D polyacrylamide gel electrophoresis and immunoreacted with the patient's serum. The results of mass spectrometric analysis revealed that the main antigen was a protein with similarity to protein z-type serpin. Notably, the identified antigen had a molecular weight of 20-25 kDa, which is markedly smaller than that previously reported for protein Z4 (44 kDa). Taken together, these analyses indicate that a possible new antigen which belongs to the protein Z family elicits immediate hypersensitivity to beer. PMID:26661797

  19. Hypersensitivity reactions to carboplatin in children.

    PubMed

    Lazzareschi, Ilaria; Ruggiero, Antonio; Riccardi, Riccardo; Attinà, Giorgio; Colosimo, Cesare; Lasorella, Anna

    2002-05-01

    Hypersensitivity reactions to carboplatin are rare but sometimes life-threatening events may occur requiring discontinuation of treatment. In our study, we describe clinical features and diagnostic procedures of carboplatin-associated reactions in children affected by low-grade astrocytoma and treated with multiple courses of carboplatin. In 6 out of 29 children, we reported allergic events. We also report a desensitization protocol for carboplatin administration, which allowed the patients to receive effective treatment without adverse reactions.

  20. Shellfish hypersensitivity: clinical and immunological characteristics.

    PubMed

    Castillo, R; Carrilo, T; Blanco, C; Quiralte, J; Cuevas, M

    1994-01-01

    Shellfish is one of the most frequent causes of food allergy. We studied 48 patients (25 male and 23 female) with a mean age of 24.2 +/- 1.8 with shellfish hypersensitivity. A clinical questionnaire was carried out and prick tests were performed using a series of aeroallergens and a battery of extracts of squid, shrimp, lobster, crab, mussel and clam. Prick tests were also performed using raw and boiled extracts from fresh squid, octopus and limpet. Total and specific IgE to these allergens were determined. The most frequent causes of symptoms were shrimp (33 cases) and squid (24 cases). The most frequently found symptoms were Urticaria/angioedema (39 patients), asthma (18 patients) and rhinitis (14 patients). Clinical association was found between Cephalopoedae and Lamelibranquiae (p < 0.05 for clam and p < 0.01 for mussel), but not among both groups and Crustaceans. Association between history and Prick was statistically significant for Crustaceae and Cephalopoedae (p < 0.01) but not for Lamalibranquiae. Association between history and CAP was not found for shellfish. Significant differences among prick-tests with raw and boiled extracts were not found. These results suggest that prick test yields better results than CAP does it, in shellfish hypersensitivity, that clinical association among shellfish hypersensitivity can occurs within the same and different Phylum reflecting common epitopes and that squid, octopus and limpet extracts contain a large amount of heat-stable allergens. PMID:8059680

  1. Chapter 28: Classification of hypersensitivity reactions.

    PubMed

    Uzzaman, Ashraf; Cho, Seong H

    2012-01-01

    The original Gell and Coomb's classification categorizes hypersensitivity reactions into four subtypes according to the type of immune response and the effector mechanism responsible for cell and tissue injury: type I, immediate or IgE mediated; type II, cytotoxic or IgG/IgM mediated; type III, IgG/IgM immune complex mediated; and type IV, delayed-type hypersensitivity or T-cell mediated. The classification has been improved so that type IIa is the former type II and type IIb is antibody-mediated cell stimulating (Graves Disease and the "autoimmune" type of chronic idiopathic urticaria). Type IV has four major categories: type IVa is CD4(+)Th1 lymphocyte mediated with activation of macrophages (granuloma formation and type I diabetes mellitus); type IVb is CD4(+)Th2 lymphocyte mediated with eosinophilic involvement (persistent asthma and allergic rhinitis); type IVc is cytotoxic CD8(+) T lymphocyte with involvement of perforin-granzme B in apoptosis (Stevens-Johnson syndrome and toxic epidermal necrolysis); type IVd is T-lymphocyte-driven neutrophilic inflammation (pustular psoriasis and acute generalized exanthematous pustulosis). Some diseases have multiple types of immunologic hypersensitivity.

  2. Stent hypersensitivity and infection in sinus cavities

    PubMed Central

    Soufras, George D.; Hahalis, George

    2013-01-01

    Persistent mucosal inflammation, granulation tissue formation, hypersensitivity, and multifactorial infection are newly described complications of retained drug-eluting stents from endoscopic sinus surgery for refractory rhinosinusitis. In an important report published in Allergy and Rhinology, a 45-year-old male patient suffering from recalcitrant chronic rhinosinusitis underwent functional endoscopic sinus surgery and was found, for the first time, to have steroid-eluting catheters that were inadvertently left in the ethmoid and frontal sinuses. The retained catheters had caused persistent mucosal inflammation and formation of granulation tissue denoting hypersensitivity reaction. These consequences had induced perpetuation of symptoms of chronic rhinosinusitis. Meticulous removal of the retained stents with the nitinol wings from inflamed tissues of the frontal, ethmoidal, and sphenoethmoidal recesses in which they were completely imbedded was successfully performed without polypoid regrowth. Cultures of specimens taken from both left and right stents showed heavy growth of Stenotrophomonas maltophilia and moderate growth of Klebsiella oxytoca, coagulase negative Staphylococcus, and beta-hemolytic Streptococcus anginosus. Fungal infection was not detected. The current knowledge and experience regarding stent hypersensitivity and infection in relation with the use of stents in sinus cavities is reviewed. PMID:24498522

  3. Drug Hypersensitivity: Pharmacogenetics and Clinical Syndromes

    PubMed Central

    Phillips, Elizabeth J.; Chung, Wen-Hung; Mockenhaupt, Maja; Roujeau, Jean-Claude; Mallal, Simon A.

    2011-01-01

    Severe cutaneous adverse reactions (SCARs) include syndromes such as drug reaction, eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) and Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN). An important advance has been the discovery of associations between HLA alleles and many of these syndromes including abacavir hypersensitivity reaction, allopurinol DRESS/DIHS and SJS/TEN and SJS/TEN associated with aromatic amine anticonvulsants. These HLA associations have created the promise for prevention through screening and have additionally shed further light on the immunopathogenesis of SCARs. The roll-out of HLA-B*5701 into routine clinical practice as a genetic screening test to prevent abacavir hypersensitivity provides a translational roadmap for other drugs. Numerous hurdles exist in the widespread translation of several other drugs such as carbamazepine where the positive predictive value of HLA-B*1502 is low and the negative predictive value of HLA-B*1502 for SJS/TEN may not be 100% in all ethnic groups. International collaborative consortia have been formed with the goal of developing phenotype standardization and undertaking HLA and genome-wide analyses in diverse populations with these syndromes. PMID:21354501

  4. Hypersensitivity reactions to iodinated contrast media.

    PubMed

    Guéant-Rodriguez, Rosa-Maria; Romano, Antonino; Barbaud, Annick; Brockow, Knut; Guéant, Jean-Louis

    2006-01-01

    Adverse reactions after iodinate contrast media (ICM) administration have been observed, which can be classified as immediate (i.e., occurring within one hour after administration) and delayed or non-immediate (i.e., occurring more than one hour after administration). Even though the incidence of ICM adverse reactions has been significantly reduced by the introduction of non-ionic compounds, immediate reactions still occur in about 3% of administrations. Different pathogenic mechanisms have been suggested for ICM reactions, including immunologic ones. Basophils and mast cells participate in immediate reactions through the release of mediators like histamine and tryptase, whereas a T-cell-mediated pathogenic mechanism is involved in most non-immediate reactions, particularly maculopapular rashes. Skin tests and specific IgE assays are carried out to diagnose immediate hypersensitivity reactions, while both delayed-reading intradermal tests and patch tests are usually performed to evaluate non-immediate reactions. However, in vitro specific IgE assays are not commercially available. As far as in vitro tests are concerned, a response involving ICM-related T-cell activity may be assessed by the lymphocyte transformation test. Allergologic evaluation appears to be indicated in hypersensitivity reactions to ICM, although the sensitivity, specificity, and predictive values of allergologic tests have not yet been established. This paper summarizes the current state of the art and addresses the research that is still needed on the pathogenic mechanisms, diagnosis, and prevention of ICM-induced hypersensitivity reactions.

  5. Diagnosis and treatment of dentinal hypersensitivity.

    PubMed

    Porto, Isabel C C M; Andrade, Ana K M; Montes, Marcos A J R

    2009-09-01

    This bibliographic review provides a general view of the etiology, characteristics and treatment of dentinal hypersensitivity, so that professionals can use this information in the therapeutic management of this clinical condition. For this purpose, the authors have analyzed whole texts of relevant articles on the subject. This study showed that the predisposing factors associated with the causes of dentinal hypersensitivity must be controlled or eliminated, by educating the patient regarding the excessive intake of acidic food, as well as providing guidance on the proper tooth brushing technique and analysis of occlusion. Effective treatment must be preceded by a proper diagnosis, established after the exclusion of any other possible causes of the pain. These cases must be managed efficiently, quickly and permanently. The availability of a wide variety of treatment could be an indicator that there is still no effective desensitizing agent to completely resolve the patient's discomfort, or that it is difficult to treat, irrespective of the available treatment options. Even with the large number of published studies, it has not been possible to reach a consensus about the product that represents the gold standard in the treatment of dentinal hypersensitivity. PMID:19776498

  6. Shellfish hypersensitivity: clinical and immunological characteristics.

    PubMed

    Castillo, R; Carrilo, T; Blanco, C; Quiralte, J; Cuevas, M

    1994-01-01

    Shellfish is one of the most frequent causes of food allergy. We studied 48 patients (25 male and 23 female) with a mean age of 24.2 +/- 1.8 with shellfish hypersensitivity. A clinical questionnaire was carried out and prick tests were performed using a series of aeroallergens and a battery of extracts of squid, shrimp, lobster, crab, mussel and clam. Prick tests were also performed using raw and boiled extracts from fresh squid, octopus and limpet. Total and specific IgE to these allergens were determined. The most frequent causes of symptoms were shrimp (33 cases) and squid (24 cases). The most frequently found symptoms were Urticaria/angioedema (39 patients), asthma (18 patients) and rhinitis (14 patients). Clinical association was found between Cephalopoedae and Lamelibranquiae (p < 0.05 for clam and p < 0.01 for mussel), but not among both groups and Crustaceans. Association between history and Prick was statistically significant for Crustaceae and Cephalopoedae (p < 0.01) but not for Lamalibranquiae. Association between history and CAP was not found for shellfish. Significant differences among prick-tests with raw and boiled extracts were not found. These results suggest that prick test yields better results than CAP does it, in shellfish hypersensitivity, that clinical association among shellfish hypersensitivity can occurs within the same and different Phylum reflecting common epitopes and that squid, octopus and limpet extracts contain a large amount of heat-stable allergens.

  7. A non-invasive in vivo imaging system to study dissemination of bioluminescent Yersinia pestis CO92 in a mouse model of pneumonic plague.

    PubMed

    Sha, Jian; Rosenzweig, Jason A; Kirtley, Michelle L; van Lier, Christina J; Fitts, Eric C; Kozlova, Elena V; Erova, Tatiana E; Tiner, Bethany L; Chopra, Ashok K

    2013-02-01

    The gold standard in microbiology for monitoring bacterial dissemination in infected animals has always been viable plate counts. This method, despite being quantitative, requires sacrificing the infected animals. Recently, however, an alternative method of in vivo imaging of bioluminescent bacteria (IVIBB) for monitoring microbial dissemination within the host has been employed. Yersinia pestis is a Gram-negative bacterium capable of causing bubonic, septicemic, and pneumonic plague. In this study, we compared the conventional counting of bacterial colony forming units (cfu) in the various infected tissues to IVIBB in monitoring Y. pestis dissemination in a mouse model of pneumonic plague. By using a transposon mutagenesis system harboring the luciferase (luc) gene, we screened approximately 4000 clones and obtained a fully virulent, luc-positive Y. pestis CO92 (Y. pestis-luc2) reporter strain in which transposition occurred within the largest pMT1 plasmid which possesses murine toxin and capsular antigen encoding genes. The aforementioned reporter strain and the wild-type CO92 exhibited similar growth curves, formed capsule based on immunofluorescence microscopy and flow cytometry, and had a similar LD(50). Intranasal infection of mice with 15 LD(50) of CO92-luc2 resulted in animal mortality by 72 h, and an increasing number of bioluminescent bacteria were observed in various mouse organs over a 24-72 h period when whole animals were imaged. However, following levofloxacin treatment (10 mg/kg/day) for 6 days 24 h post infection, no luminescence was observed after 72 h of infection, indicating that the tested antimicrobial killed bacteria preventing their detection in host peripheral tissues. Overall, we demonstrated that IVIBB is an effective and non-invasive way of monitoring bacterial dissemination in animals following pneumonic plague having strong correlation with cfu, and our reporter CO92-luc2 strain can be employed as a useful tool to monitor the efficacy

  8. Delayed drug hypersensitivity reactions - new concepts.

    PubMed

    Posadas, S J; Pichler, W J

    2007-07-01

    Immune reactions to small molecular compounds such as drugs can cause a variety of diseases mainly involving skin, but also liver, kidney, lungs and other organs. In addition to the well-known immediate, IgE-mediated reactions to drugs, many drug-induced hypersensitivity reactions appear delayed. Recent data have shown that in these delayed reactions drug-specific CD4(+) and CD8(+) T cells recognize drugs through their T cell receptors (TCR) in an MHC-dependent way. Immunohistochemical and functional studies of drug-reactive T cells in patients with distinct forms of exanthems revealed that distinct T cell functions lead to different clinical phenotypes. Taken together, these data allow delayed hypersensitivity reactions (type IV) to be further subclassified into T cell reactions, which by releasing certain cytokines and chemokines preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd). Moreover, cytotoxic functions by either CD4(+) or CD8(+) T cells (type IVc) seem to participate in all type IV reactions. Drugs are not only immunogenic because of their chemical reactivity, but also because they may bind in a labile way to available TCRs and possibly MHC-molecules. This seems to be sufficient to stimulate certain, probably preactivated T cells. The drug seems to bind first to the fitting TCR, which already exerts some activation. For full activation, an additional interaction of the TCR with the MHC molecules is needed. The drug binding to the receptor structures is reminiscent of a pharmacological interaction between a drug and its (immune) receptor and was thus termed the p-i concept. In some patients with drug hypersensitivity, such a response occurs within hours even upon the first exposure to the drug. The T cell reaction to the drug might thus not be due to a classical, primary response, but is due to peptide-specific T cells which happen to be stimulated by a drug. This new concept has major implications

  9. Activated platelets release sphingosine 1-phosphate and induce hypersensitivity to noxious heat stimuli in vivo

    PubMed Central

    Weth, Daniela; Benetti, Camilla; Rauch, Caroline; Gstraunthaler, Gerhard; Schmidt, Helmut; Geisslinger, Gerd; Sabbadini, Roger; Proia, Richard L.; Kress, Michaela

    2015-01-01

    At the site of injury activated platelets release various mediators, one of which is sphingosine 1-phosphate (S1P). It was the aim of this study to explore whether activated human platelets had a pronociceptive effect in an in vivo mouse model and whether this effect was based on the release of S1P and subsequent activation of neuronal S1P receptors 1 or 3. Human platelets were prepared in different concentrations (105/μl, 106/μl, 107/μl) and assessed in mice with different genetic backgrounds (WT, S1P1fl/fl, SNS-S1P1−/−, S1P3−/−). Intracutaneous injections of activated human platelets induced a significant, dose-dependent hypersensitivity to noxious thermal stimulation. The degree of heat hypersensitivity correlated with the platelet concentration as well as the platelet S1P content and the amount of S1P released upon platelet activation as measured with LC MS/MS. Despite the significant correlations between S1P and platelet count, no difference in paw withdrawal latency (PWL) was observed in mice with a global null mutation of the S1P3 receptor or a conditional deletion of the S1P1 receptor in nociceptive primary afferents. Furthermore, neutralization of S1P with a selective anti-S1P antibody did not abolish platelet induced heat hypersensitivity. Our results suggest that activated platelets release S1P and induce heat hypersensitivity in vivo. However, the platelet induced heat hypersensitivity was caused by mediators other than S1P. PMID:25954148

  10. Acute interstitial pneumonitis. Case series and review of the literature.

    PubMed

    Vourlekis, J S; Brown, K K; Cool, C D; Young, D A; Cherniack, R M; King, T E; Schwarz, M I

    2000-11-01

    Acute interstitial pneumonitis (AIP) is an acute, idiopathic interstitial lung disease characterized by rapidly progressive diffuse pulmonary infiltrates and hypoxemia requiring hospitalization. The case-fatality ratio is high. Previous reports suggested that survivors of the acute event have a favorable outcome. We undertook this study to examine the natural history of survivors. We had observed several patients who experienced recurrent episodes of AIP and chronic progressive interstitial lung disease. We sought to determine longitudinal survival in these patients and to compare our experience with that in the medical literature. Overall, we identified 13 biopsy-proven cases of AIP. The mean patient age was 54 years in our review, which is identical to previous reports. Twelve patients were hospitalized and all 12 required mechanical ventilation. Overall hospital survival was 67%. All patients demonstrated abnormalities in gas exchange at presentation. Radiographs typically demonstrated bilateral patchy densities that progressed to a diffuse alveolar filling pattern in nearly all cases. All biopsy specimens showed organizing diffuse alveolar damage. Longitudinal data were available for 7 patients. Two died of AIP recurrences. A third died of complications of heart failure shortly after hospital discharge. One patient progressed to end-stage lung disease and required lung transplantation. Two patients experienced persistent pulmonary symptoms, accompanied in 1 by progressive lung fibrosis. One patient had nearly complete recovery of lung function 2 years following AIP. (Follow-up information was unavailable for 2 survivors.) In our literature review, 5 of 7 patients reported experienced some recovery of lung function. One case of progressive interstitial lung disease requiring lung transplantation was reported. The reported mortality was much higher than in our experience (74% versus 33%). The mean time from symptom onset to death was 26 days, compared with 34

  11. Absence of cross-reactivity to carbapenems in patients with delayed hypersensitivity to penicillins.

    PubMed

    Romano, A; Gaeta, F; Valluzzi, R L; Alonzi, C; Maggioletti, M; Zaffiro, A; Caruso, C; Quaratino, D

    2013-12-01

    Studies performed on subjects with IgE-mediated hypersensitivity to penicillins have demonstrated a 1% rate of cross-reactivity between penicillins and both imipenem and meropenem, while a single study found a 5.5% rate of cross-reactivity with imipenem/cilastatin in subjects with T-cell-mediated hypersensitivity to β-lactams, mostly penicillins. We studied 204 consecutive subjects with a well-demonstrated T-cell-mediated hypersensitivity to assess the cross-reactivity with carbapenems and the tolerability of such alternative β-lactams. All 204 subjects underwent skin tests with imipenem/cilastatin and meropenem; 130 of them were skin-tested also with ertapenem. Subjects with negative test results were challenged with these carbapenems. All subjects displayed negative skin tests to carbapenems and tolerated challenges. These data demonstrate the absence of clinically significant T-cell-mediated cross-reactivity between penicillins and carbapenems. Negative delayed-reading skin testing with carbapenems in individuals with documented T-cell-mediated hypersensitivity to penicillins correlates well with subsequent clinical tolerance of therapeutic doses of carbapenems.

  12. Immediate and Delayed Hypersensitivity Reactions to Corticosteroids: Evaluation and Management.

    PubMed

    Otani, Iris M; Banerji, Aleena

    2016-03-01

    Corticosteroids are anti-inflammatory medications used widely to treat allergic inflammation. Although the endocrine and gastrointestinal side effects of corticosteroids have been described, the occurrence of immediate hypersensitivity reactions and delayed contact dermatitis due to corticosteroids remains under-recognized. Hypersensitivity reactions can occur to a corticosteroid itself, or to the additives and vehicles in corticosteroid preparations. Skin testing and oral graded challenge can help confirm the suspected culprit agent in immediate hypersensitivity reactions and help identify an alternative tolerated corticosteroid. Patch testing can help identify the culprit agents in delayed hypersensitivity contact dermatitis. Cross-reactivity patterns have not been observed for immediate hypersensitivity reactions as they have been for delayed contact dermatitis. Sensitization in contact dermatitis exhibits cross-reactivity patterns based on corticosteroid structure. We review the current understanding regarding the clinical presentation, evaluation, and management of immediate and delayed hypersensitivity reactions to corticosteroids.

  13. A physiologic differentiation between delayed and immediate hypersensitivity

    PubMed Central

    Apicella, Michael A.; Allen, James C.

    1969-01-01

    Studies have been made of movement of various macromolecules into and out of the pleural space of guinea pigs during the course of a delayed hypersensitivity reaction to purified protein derivative (PPD), and a passively transferred immediate hypersensitivity reaction to ovalbumin. While the immediate hypersensitivity reaction transiently alters vascular permeability as shown by increased movement of macromolecules into the chest, the delayed hypersensitivity reaction is marked by a decreased capacity to resorb macromolecules from the pleural space. The data suggest that the two hypersensitivity reactions may be distinguished by these physiologic differences. Additional data from studies of a chemically induced pleural effusion in these animals suggest that some type of outflow obstruction is necessary for the development of effusion, but that the outflow defect caused by the irritating chemical is based on a different mechanism than that seen during the delayed hypersensitivity reaction. PMID:4179171

  14. 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.

  15. Nitric oxide mediates murine cytomegalovirus-associated pneumonitis in lungs that are free of the virus.

    PubMed Central

    Tanaka, K; Nakazawa, H; Okada, K; Umezawa, K; Fukuyama, N; Koga, Y

    1997-01-01

    4 wk after intraperitoneal inoculation of 0.2 LD50 (50% lethal dose) of murine cytomegalovirus (MCMV) in adult BALB/c mice, MCMV remained detectable in the salivary glands, but not in the lungs or other organs. When the T cells of these mice were activated in vivo by a single injection of anti-CD3 monoclonal antibody, interstitial pneumonitis was induced in the lungs that were free of the virus with an excessive production of the cytokines. In the lungs of such mice persistently infected with MCMV, the mRNA of the cytokines such as IL-2, IL-6, TNF-alpha, and IFN-gamma were abundantly expressed 3 h after the anti-CD3 injection, and the elevated levels continued thereafter. A marked expression of inducible nitric oxide synthetase (iNOS) was then noted in the lungs, suggesting that such cytokines as TNF-alpha and IFN-gamma may have induced iNOS. Although the increase in NO formation was demonstrated by the significant elevation of the serum levels of nitrite and nitrate, the interstitial pneumonitis was not associated with either increased superoxide formation or peroxynitrite-induced tyrosine nitration. Nevertheless, the administration of an NO antagonist also alleviated the interstitial pneumonitis provoked by anti-CD3 mAb. Based on these findings, it was concluded that MCMV-associated pneumonitis is mediated by a molecule of cytokine-induced NO other than peroxynitrite. PMID:9312183

  16. 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.

  17. 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

  18. New insights into visceral hypersensitivity--clinical implications in IBS.

    PubMed

    Zhou, QiQi; Verne, G Nicholas

    2011-06-01

    A subset of patients with IBS have visceral hypersensitivity and/or somatic hypersensitivity. Visceral hypersensitivity might have use as a clinical marker of IBS and could account for symptoms of urgency for bowel movements, bloating and abdominal pain. The mechanisms that lead to chronic visceral hypersensitivity in patients who have IBS are unclear. However, several working models may be considered, including: nociceptive input from the colon that leads to hypersensitivity; increased intestinal permeability that induces a visceral nociceptive drive; and alterations in the expression of microRNAs in gastrointestinal tissue that might be delivered via blood microvesicles to other target organs, such as the peripheral and/or central nervous system. As such, the chronic visceral hypersensitivity that is present in a subset of patients with IBS might be maintained by both peripheral and central phenomena. The theories underlying the development of chronic visceral hypersensitivity in patients with IBS are supported by findings from new animal models in which hypersensitivity follows transient inflammation of the colon. The presence of somatic hypersensitivity and an alteration in the neuroendocrine system in some patients who have IBS suggests that multisystemic factors are involved in the overall disorder. Thus, IBS is similar to other chronic pain disorders, such as fibromyalgia, chronic regional pain disorder and temporomandibular joint disorder, as chronic nociceptive mechanisms are activated in all of these disorders.

  19. Titanium hypersensitivity. A hidden threat for dental implant patients?

    PubMed

    Bilhan, Hakan; Bural, Canan; Geckili, Onur

    2013-01-01

    Titanium and its alloys have been widely used for dental prosthetic devices because of their superior mechanical properties and biocompatibility. However, the incidence of titanium hypersensitivity or allergy is still unknown and the discussion about its existence is ongoing. Unexplained implant failures have also forced dental clinicians to investigate the possibility of titanium hypersensitivity or allergy. This review focuses on the potential of dental implant-related titanium hypersensitivity or allergic reactions. It includes an examination of the existing scientific literature and current knowledge. Evidence-based data and studies related to titanium hypersensitivity in dental implant patients are also discussed.

  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.

  1. 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

  2. Early events in plant hypersensitive response leaves revealed by IR thermography

    NASA Astrophysics Data System (ADS)

    Boccara, Martine; Boue, Christine; De Paepe, Rosine; Boccara, Albert C.

    2001-10-01

    Infrared thermography is used to reveal the establishment of Erwinia amylovora harpin-induced hypersensitive response (HR) in Nicotiana sylvestris leaves. We observed a decrease in temperature (1-2 degree(s)C) in the harpin infiltrated zone, correlated with an increase in stomatal opening, strongly suggesting that the temperature decrease is due to higher transpiration rate. IRT experiments were conducted in a laboratory environment and could be widely applied for genotype screening and monitoring drug effects.

  3. Lymphocyte transformation studies in drug hypersensitivity

    PubMed Central

    Warrington, R.J.; Tse, K.S.

    1979-01-01

    In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents. Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects. For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test. It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs. PMID:445303

  4. Hypersensitivity and nanoparticles: update and research trends

    PubMed Central

    MOCAN, TEODORA; MATEA, CRISTIAN T.; IANCU, CORNEL; AGOSTON-COLDEA, LUCIA; MOCAN, LUCIAN; ORASAN, REMUS

    2016-01-01

    Nanotechnology holds a great promise for a wide range of medical-intent applications (diagnostic, treatment and prophylaxis of various diseases). Their advantages are due to their size, versatility and potential for multiple simultaneous applications. However, concerns have been formulated by scientific world due to insufficient data on toxicity of nanomaterials. One area of interest is represented by the interactions between nanoparticles and the components of the immune system. We review herein reported data on hypersensitivity reactions. The role exerted by nanoparticles in both immunostimulation and immunosuppression in allergen-driven mechanisms was studied, as well as future trends in worldwide research. PMID:27152071

  5. Dentin hypersensitivity: differential diagnosis, tests, and etiology.

    PubMed

    Trushkowsky, Richard D; Garcia-Godoy, Franklin

    2014-02-01

    Dentin hypersensitivity (DHS) is a painful condition that affects up to 57 percent of the adult population. It occurs as a result of exposure of dentin to the oral environment. Ensuring the correct diagnosis of this condition is based on history and examination. An oral screening for DHS should encompass such elements as patient history, clinical examination that includes radiographs, a variety of tests, identification of risk factors, and a differential diagnosis. An understanding of dentinal fluid and odontoblasts is also beneficial for diagnosis. PMID:24571559

  6. Hemolysate-mediated renal vasoconstriction and hypersensitization.

    PubMed

    Burke, T J; Falk, S; Conger, J D; Voelkel, N F

    1999-01-01

    The present studies measured vessel diameter, before and after addition of hemolysate, in isolated afferent arterioles (AA) and efferent arterioles (EA) obtained from the rat kidney. Human red blood cells (RBC) were hemolyzed in distilled water and membranes were discarded after centrifugation. Hemolysate added to the bath solution caused vigorous AA and EA contraction and, after washout, hypersensitized the AA and EA to doses of angiotensin II (AII) which would normally only elicit 50% contraction (EC50). Neither the contraction nor the hypersensitization were mimicked by pure human hemoglobin. The vasoconstrictive responses in the AA and EA were accompanied by increased cytosolic-free calcium concentration. Further purification (desalting) of the hemolysate to remove substance of < or = 1000 Da (which include ATP) did not eliminate the vasoconstrictive component from the hemolysate. Finally, cultured rat aortic vascular smooth muscle cells also demonstrated a rapid increase in (Ca2+i) when exposed to hemolysate. This increase in (Ca2+i) was, in part, dependent on Ca2+ influx since it could be attenuated with diltiazem (10(-5) M). In conclusion, hemolysate contains a factor which induces contractions of the isolated rat kidney AA and EA and rapid elevations in (Ca2+i). This factor, from hemolyzed RBC, is not hemoglobin itself. PMID:10048115

  7. Are Some Neurons Hypersensitive to Metallic Nanoparticles?

    PubMed Central

    Scott, Bobby R.

    2010-01-01

    Engineered metallic nanomaterial particles (MENAP) represent a significant breakthrough in developing new products for use by consumers and industry. Skin application (e.g., via creams and sprays containing nanoparticles) may provide a key route of potential intake of MENAP and can lead to retrograde transport from nerve endings in the skin to the somatosensory neurons in dorsal root ganglia (DRG). This paper uses a novel theoretical model (stochastic threshold microdose [STM] model) to characterize survival of DRG neurons exposed in cell culture replicates to copper nanoparticles, based on published data. Cell death via autophagy is assumed here to occur as a result of the uptake (called hits) of the nanoparticles by mitochondria. Theoretical results are presented for the existence of a hypersensitive fraction (about 20%) of neurons that are killed in significant numbers when on average > 1 hit to the at-risk mitochondria occurs. Further, most hypersensitive neurons appear to be killed by a cumulative exposure of about 2,000 micromolar-hours and the remaining resistant cells may have dysfunctional mitochondria. Based on these theoretical findings, it is predicted that repeated exposure (e.g., over years) of the skin of humans to MENAP could lead to significant nervous system damage and related morbidity. PMID:22423227

  8. In vitro evidence of delayed-type hypersensitivity to hydrocortisone.

    PubMed

    Wilkinson, S M; English, J S; Mattey, D L

    1993-11-01

    Hypersensitivity to topical hydrocortisone is becoming increasingly recognized. We present further evidence that this is mediated via a delayed-type hypersensitivity reaction. A hydrocortisone: albumin complex was able to induce a proliferative response in the peripheral blood mononuclear cells of patients allergic to hydrocortisone. Protein binding of hydrocortisone or a degradation product may be important in the development of corticosteroid allergy.

  9. Teenagers' experiences of living with food hypersensitivity: a qualitative study.

    PubMed

    MacKenzie, Heather; Roberts, Graham; van Laar, Darren; Dean, Taraneh

    2010-06-01

    Teenagers are a high-risk group for food-hypersensitivity fatalities, engage in risk-taking behaviours and may experience impaired quality of life. Understanding their experience is important to inform their care. This study aimed to describe the lived experiences of teenagers with food hypersensitivity. Individual semi-structured interviews were conducted with 21 teenagers (13-18 yr) with food hypersensitivity to a variety of foods and analysed using a phenomenological approach. Teenagers described living with (or coming to know) food hypersensitivity (FHS) as a way of life but still found living with food hypersensitivity to be burdensome. A necessary part of living with food hypersensitivity was coping with associated burden; a variety of coping strategies were employed to this effect. Teenagers described ways in which the burden of living with food hypersensitivity was alleviated or exacerbated by others. Management of food hypersensitivity was based on an assessment of acceptable risk resulting in varying levels of precaution taking. Teenagers' understanding of their FHS and ability to cope with it needs to be regularly assessed. Educational support may be required to ensure they take an appropriate level of precautions to minimize the chance of future reactions while not over compromising their quality of life. Psychological support may be required to help them to utilize healthy adaptive strategies to cope with the stresses of living with FHS. This approach is also likely to facilitate the smooth handover of responsibility from parent to teenager.

  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. [A welder with chemical pneumonitis caused by inhalation of zinc fume].

    PubMed

    Tojima, H; Ando, T; Kishikawa, H; Tokudome, T

    1998-04-01

    A 61-year-old man with a 32-year occupational history of welding developed malaise, cough, and dyspnea after inhalation of smoke while welding galvanized steel. On admission, peripheral leukocytosis, hypoxemia, and diffuse granular and linear opacities on a chest X-ray were present. The bronchioli were exaggerated in a chest high-resolution CT. Bronchoalveolar lavage revealed mild lymphocytosis and transbronchial lung biopsy showed siderosis and exudation of fibrin and neutrophils into alveolar spaces. The clinical and radiographic findings later improved except for an obstructive disorder on pulmonary function test. The respiratory health hazards associated with welding vary according to the materials and the concentration of inhaled substances. Acute chemical pneumonitis caused by inhalation of zinc fumes (zinc oxide) was accompanied by chronic siderosis in this case. It is well known that metal fume fever commonly occurs when inhaling zinc oxide fumes. However acute chemical pneumonitis after exposure to zinc oxide during welding has been only rarely reported.

  12. Prevention of bubonic and pneumonic plague using plant-derived vaccines.

    PubMed

    Alvarez, M Lucrecia; Cardineau, Guy A

    2010-01-01

    Yersinia pestis, the causative agent of bubonic and pneumonic plague, is an extremely virulent bacterium but there are currently no approved vaccines for protection against this organism. Plants represent an economical and safer alternative to fermentation-based expression systems for the production of therapeutic proteins. The recombinant plague vaccine candidates produced in plants are based on the two most immunogenic antigens of Y. pestis: the fraction-1 capsular antigen (F1) and the low calcium response virulent antigen (V) either in combination or as a fusion protein (F1-V). These antigens have been expressed in plants using all three known possible strategies: nuclear transformation, chloroplast transformation and plant-virus-based expression vectors. These plant-derived plague vaccine candidates were successfully tested in animal models using parenteral, oral, or prime/boost immunization regimens. This review focuses on the recent research accomplishments towards the development of safe and effective pneumonic and bubonic plague vaccines using plants as bioreactors.

  13. Controlling Ebola: what we can learn from China's 1911 battle against the pneumonic plague in Manchuria.

    PubMed

    Liu, He; Jiao, Mingli; Zhao, Siqi; Xing, Kai; Li, Ye; Ning, Ning; Liang, Libo; Wu, Qunhong; Hao, Yanhua

    2015-04-01

    The pneumonic plague, which spread across Northeast China during the winter of 1910 and spring of 1911, caused numerous deaths and brought about severe social turmoil. After compulsory quarantine and other epidemic prevention measures were enforced by Dr Wu Lien-teh, the epidemic was brought to an end within 4 months. This article reviews the ways in which the plague was dealt with from a historical perspective, based on factors such as clinical manifestations, duration of illness, case fatality rate, degree of transmissibility, poverty, inadequate healthcare infrastructure, and the region's recent strife-filled history. Similarities were sought between the pneumonic plague in Northeast China in the twentieth century and the Ebola virus outbreak that is currently ravaging Africa, and an effort made to summarize the ways in which specific measures were applied successfully to fight the earlier epidemic. Our efforts highlight valuable experiences that are of potential benefit in helping to fight the current rampant Ebola epidemic in West Africa.

  14. Septic pneumonic tularaemia caused by Francisella tularensis subsp. holarctica biovar II.

    PubMed

    Fritzsch, Joerg; Splettstoesser, Wolf D

    2010-09-01

    This case of pneumonic tularaemia elucidates two aspects: it is believed to be the first documented case of bacteraemia caused by Francisella tularensis subsp. holarctica biovar II; furthermore, it illustrates the remission of septic pneumonic tularaemia without appropriate anti-infective therapy. A blood culture from a patient with community-acquired pneumonia was found to be positive for F. tularensis subsp. holarctica biovar II after 10 days of cultivation. Meanwhile, the patient had been treated with ceftriaxone, followed by sultamicillin and clindamycin. The patient continued suffering from fever of up to 40.7 degrees C and rising C-reactive protein (CRP) for 4 days before the fever and CRP declined. The isolated strain was later tested and found to be resistant to the antibiotics used. The present case underlines that F. tularensis subsp. holarctica infections may cause severe symptoms but mostly have a favourable outcome.

  15. Visceral hypersensitive rats share common dysbiosis features with irritable bowel syndrome patients

    PubMed Central

    Zhou, Xiao-Yan; Li, Ming; Li, Xia; Long, Xin; Zuo, Xiu-Li; Hou, Xiao-Hua; Cong, Ying-Zi; Li, Yan-Qing

    2016-01-01

    AIM: To evaluate gut microbial dysbiosis in two visceral hypersensitive models in comparison with irritable bowel syndrome (IBS) patients and to explore the extent to which these models capture the dysbiosis of IBS patients. METHODS: Visceral hypersensitivity was developed using the maternal separation (MS) rat model and post-inflammatory rat model. The visceral sensitivity of the model groups and control group was evaluated using the abdominal withdraw reflex score and electromyography in response to graded colorectal distention. The 16S ribosomal RNA gene from fecal samples was pyrosequenced and analyzed. The correlation between dysbiosis in the microbiota and visceral hypersensitivity was calculated. Positive findings were compared to sequencing data from a published human IBS cohort. RESULTS: Dysbiosis triggered by neonatal maternal separation was lasting but not static. Both MS and post-inflammatory rat fecal microbiota deviated from that of the control rats to an extent that was larger than the co-housing effect. Two short chain fatty acid producing genera, Fusobacterium and Clostridium XI, were shared by the human IBS cohort and by the maternal separation rats and post-inflammatory rats, respectively, to different extents. Fusobacterium was significantly increased in the MS group, and its abundance positively correlated with the degree of visceral hypersensitivity. Porphyromonadaceae was a protective biomarker for both the rat control group and healthy human controls. CONCLUSION: The dysbiosis MS rat model and the post-inflammatory rat model captured some of the dysbiosis features of IBS patients. Fusobacterium, Clostridium XI and Porphyromonadaceae were identified as targets for future mechanistic research. PMID:27298564

  16. Drug hypersensitivity syndrome with significant gastrointestinal involvement.

    PubMed

    Chung, Wan-Ling; Teo, Lynn; Wang, Yi-Shi; Liu, Tsun-Tsien

    2012-11-01

    Drug hypersensitivity syndrome (DHS) is an idiosyncratic systemic reaction to a drug. The clinical presentation of this syndrome comprises a diverse spectrum, ranging from mild to fulminating organ failure. Nonspecific gastrointestinal symptoms are common in DHS, but severe morbidities and mortalities attributed to gut disease in DHS are rarely described. We present a case of DHS with significant gastrointestinal symptoms of prolonged profuse watery diarrhoea and persistent hypokalaemia requiring judicious intravenous water and electrolyte replacement. The symptoms resolved only after the introduction of intravenous hydrocortisone. It is important to consider intravenous corticosteroids if the gastrointestinal system is involved, as accelerated gut motility and mucosal damage would affect absorption of oral medications. Supportive treatment with the monitoring of fluid and electrolytes status and judicious replacement remains fundamental in the management of DHS patients with gut involvement.

  17. Non-surgical management of tooth hypersensitivity.

    PubMed

    Clark, Danielle; Levin, Liran

    2016-10-01

    Tooth sensitivity is a common complaint of patients in dental practices. Studies have demonstrated dentinal hypersensitivity to affect 10-30% of the population. There are various potential causes of tooth sensitivity and a variety of available treatment options. This narrative review will discuss the possible aetiology of this condition, as well as the treatment modalities available. A tailor-made treatment plan that starts with the most non-invasive treatment options and escalates only when those options have proven insufficient in alleviating symptoms should be provided for each patient. Only after all non- and less-invasive methods have failed to reduce the symptoms should more invasive treatment options, such as root-coverage, be considered. PMID:27301300

  18. Radiation pneumonitis: a complication resulting from combined radiation and chemotherapy for early breast cancer

    SciTech Connect

    Gez, E.; Sulkes, A.; Isacson, R.; Catane, R.; Weshler, Z.

    1985-10-01

    Described is a patient with early breast carcinoma who developed clinical radiation pneumonitis during primary radiation therapy and concomitant chemotherapy that included prednisone. This syndrome developed three days following abrupt steroid withdrawal. Retrieval of steroids brought complete resolution of the clinical and radiological findings. Although this syndrome is rare, it is recommended that steroid therapy in a patient previously irradiated to the chest be avoided.

  19. Experimental model of swine pneumonic pasteurellosis using crude Actinobacillus pleuropneumoniae cytotoxin and Pasteurella multocida given endobronchially.

    PubMed Central

    Chung, W B; Bäckström, L R; Collins, M T

    1994-01-01

    This study was designed to develop and characterize a swine pneumonic pasteurellosis model by concurrent introduction of Pasteurella multocida type A and Actinobacillus pleuropneumoniae crude cytotoxin. After a series of preliminary experiments, a combination of 4 x 10(9) P. multocida and 4,000 toxic units of A. pleuropneumoniae crude cytotoxin was determined to produce optimal results. A total of 48 pigs were divided into four groups of 12 pigs each. The control group received buffered saline only. Four pigs from each group were randomly selected for necropsy 3, 7 and 14 days postinoculation (PI). Inoculation of pigs with P. multocida and A. pleuropneumoniae cytotoxin (group 1) resulted in moderate to severe pneumonia. Pasteurella multocida was isolated from pneumonic lesions, grossly normal lung, and bronchial lymph nodes of all group 1 pigs throughout the 14 day experimental period. Pathological changes typical of field cases of swine pneumonic pasteurellosis were produced. Pigs inoculated with P. multocida alone (group 2) had pneumonic lesions and P. multocida was reisolated from lungs at three days PI. Pasteurella multocida was not isolated from these pigs at 7 and 14 days PI, except for one pig in which an abscess developed in the thorax. Pulmonary lesions induced by A. pleuropneumoniae crude cytotoxin alone (group 3) were transient and resolved by seven days PI. Group 1 pigs had significantly greater lung lesion volumes than group 2 and 3 pigs at 3, 7 and 14 days PI. Statistical analysis indicated a significant interactive effect of P. multocida and A. pleuropneumoniae cytotoxin on the development of lung lesion volumes at 7 and 14 days PI (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) Images Fig. 1. PMID:8143249

  20. Late-onset methotrexate-induced pneumonitis with neutrophilia in bronchoalveolar lavage fluid

    PubMed Central

    Yamakawa, Hideaki; Yoshida, Masahiro; Takagi, Masamichi; Kuwano, Kazuyoshi

    2014-01-01

    A 61-year-old woman being treated with methotrexate (MTX) 8–10 mg/week and prednisolone 2.5 mg/day for rheumatoid arthritis presented with a 1-week history of increasing fever and dry cough. The patient deteriorated with administration of antibiotics. Chest CT scan showed bilateral diffuse ground-glass opacities. Analysis of bronchoalveolar lavage fluid (BALF) revealed marked neutrophilia (65.2% of total cells). The specimen from transbronchial lung biopsy showed a non-specific interstitial pneumonia pattern. Following withdrawal of the MTX, her pulmonary infiltration, clinical symptoms and laboratory findings gradually improved. Therefore, she was diagnosed as having MTX-induced pneumonitis. Lymphocytosis in BALF has been identified as a characteristic of MTX-induced pneumonitis, particularly in late onset of this disease. However, the BALF in our patient was neutrophilic. Although neutrophilia in BALF of patients with drug-induced pneumonitis is usually associated with poor outcome, rare cases of good outcome do exist. PMID:25267808

  1. The yersiniabactin transport system is critical for the pathogenesis of bubonic and pneumonic plague.

    PubMed

    Fetherston, Jacqueline D; Kirillina, Olga; Bobrov, Alexander G; Paulley, James T; Perry, Robert D

    2010-05-01

    Iron acquisition from the host is an important step in the pathogenic process. While Yersinia pestis has multiple iron transporters, the yersiniabactin (Ybt) siderophore-dependent system plays a major role in iron acquisition in vitro and in vivo. In this study, we determined that the Ybt system is required for the use of iron bound by transferrin and lactoferrin and examined the importance of the Ybt system for virulence in mouse models of bubonic and pneumonic plague. Y. pestis mutants unable to either transport Ybt or synthesize the siderophore were both essentially avirulent via subcutaneous injection (bubonic plague model). Surprisingly, via intranasal instillation (pneumonic plague model), we saw a difference in the virulence of Ybt biosynthetic and transport mutants. Ybt biosynthetic mutants displayed an approximately 24-fold-higher 50% lethal dose (LD(50)) than transport mutants. In contrast, under iron-restricted conditions in vitro, a Ybt transport mutant had a more severe growth defect than the Ybt biosynthetic mutant. Finally, a Delta pgm mutant had a greater loss of virulence than the Ybt biosynthetic mutant, indicating that the 102-kb pgm locus encodes a virulence factor, in addition to Ybt, that plays a role in the pathogenesis of pneumonic plague.

  2. 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

  3. Increased prevalence of IgG-induced sensitization and hypersensitivity pneumonitis (humidifier lung) in nonsmokers exposed to aerosols of a contaminated air conditioner.

    PubMed

    Baur, X; Richter, G; Pethran, A; Czuppon, A B; Schwaiblmair, M

    1992-01-01

    Specific IgG antibodies against antigens of a contaminated air conditioner were estimated in serum of 134 workers of a printing company. Altogether 64% of the workers investigated revealed significantly elevated levels (> 3 U/ml) of IgG antibodies specific to these antigens as compared to a nonexposed control group. The occurrence of IgG antibodies for microbial extracts were 25% for Fusarium, 23% for Penicillium notatum, 13% for Alternaria tenuis, 12% for Aureobasidium pullulans, 9% for Sphaeropsidales species, 3% for Micropolyspora faeni, 2% for Aspergillus fumigatus and 2% for Thermoactionomyces vulgaris. Out of the 86 workers with elevated IgG antibodies for air conditioner antigens, 59 were nonsmokers. Considering a cut-off level of 10 U/ml IgG for high values, the proportion of smokers to nonsmokers becomes even more pronounced (6 to 36 respectively, binominal test p < 0.001). This is despite the fact that the distribution of smokers and nonsmokers among the 134 workers is approximately equal (60 to 74). All 3 workers with clinical diagnosis of humidifier lung or humidifier fever belonged to the nonsmoker group. Our findings indicate that crude water extracts of contaminated air conditioners are the best choice as antigen source for the diagnosis of humidifier lung in exposed workers. Nonsmokers are shown to have a high risk for immunological sensitization. PMID:1485005

  4. Incidence and time course of dentinal hypersensitivity after periodontal surgery.

    PubMed

    Al-Sabbagh, Mohanad; Beneduce, Carla; Andreana, Sebastiano; Ciancio, Sebastian G

    2010-01-01

    This study sought to characterize the incidence and clinical progression of dentinal hypersensitivity after periodontal surgery. Fourteen patients scheduled for open-flap periodontal debridement participated in the study. Ten subjects completed the study and were evaluated for six consecutive weeks after periodontal surgery. Tactile hypersensitivity was assessed using the Yeaple probe; thermal hypersensitivity measurements were obtained using a blast of air from the air/water syringe; and subjective hypersensitivity measurements were obtained using a visual analog scale (VAS). Measurements were taken preoperatively, one week postoperatively, and once a week for the next five consecutive weeks, for a total of six measurements after periodontal surgery. Depending on the stimuli used, dentinal hypersensitivity at one week after periodontal surgery ranged from 67 to 76%. Preoperative tactile and thermal hypersensitivity incidence combined was 30% at baseline. One week after periodontal surgery, the combined incidence had increased to 79%; at six weeks postsurgery, it had decreased to 45%. This study shows that postoperative dentinal hypersensitivity increases at one and three weeks after open-flap periodontal debridement before spontaneously and gradually decreasing to levels similar to those presurgery, even in the absence of desensitizing therapy. PMID:20129876

  5. Late-onset Anticonvulsant Hypersensitivity Syndrome Mimicking Lymphoma.

    PubMed

    Geduk, Ayfer; Birtas Atesoglu, Elif; Mehtap, Ozgur; Terzi Demirsoy, Esra; Can, Burak; Tarkun, Pinar; Hacihanefioglu, Abdullah

    2015-01-01

    Anticonvulsant hypersensitivity syndrome is a fatal, idiosyncratic drug reaction that is caused by aromatic antiepileptic drugs. This cutaneous drug reaction is also called pseudolymphoma because of its clinical and histological similarities with malignant lymphoma. The primary clinical findings are fever, skin rashes, enlarged lymph nodes, single or multiple internal organ involvement and hematological abnormalities. Typically, anticonvulsant hypersensitivity syndrome occurs 1-8 weeks after drug administration. We herein present the case of a patient who had been on anticonvulsant therapy for five years and died from late-onset anticonvulsant hypersensitivity syndrome. PMID:26666613

  6. Dentin hypersensitivity: etiology, diagnosis and treatment; a literature review.

    PubMed

    Davari, Ar; Ataei, E; Assarzadeh, H

    2013-09-01

    The objective of this review is to inform practitioners about dentin hypersensitivity (DH); to provide a brief overview of the diagnosis, etiology and clinical management of dentin hypersensitivity and to discuss technical approaches to relieve sensitivity. This clinical information is described in the context of the underlying biology. The author used PUBMED to find relevant English-language literature published in the period 1999 to 2010. The author used combinations of the search terms "dentin*", "tooth", "teeth", "hypersensit*", "desensitiz*". Abstracts and also full text articles to identify studies describing etiology, prevalence, clinical features, controlled clinical trials of treatments and relevant laboratory research on mechanisms of action were used. PMID:24724135

  7. 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

  8. Clustering of foodstuffs in food hypersensitivity. An inquiry study in pollen allergic patients.

    PubMed

    Eriksson, N E

    1984-01-01

    600 pollen allergic patients were questioned about hypersensitivity symptoms from various foodstuffs. The answers regarding one foodstuff were compared with those of other foodstuffs making 780 tables, from which the Spearmen 's correlation coefficients were calculated. Most of the combinations of foodstuffs showed statistically significant correlations. The highest value of the correlation coefficient was found for certain combinations: Various nuts reciprocally as well as nuts combined with apple and stone fruits. Stone fruits reciprocally and even stone fruits combined with apple and pear. Apple and pear. Kiwi fruit and avocado. Potato and carrot. Swede , parsnip and celery reciprocally. Strawberry and wild strawberry. Fish and bread, fish and cheese. Beer and wine. Several of the foodstuffs showing high degrees of correlation are known to be associated with birch pollen allergies. It is probable that at least some of these correlations are due to true IgE-mediated cross-reactivity with common allergens in birch pollen and foodstuffs. Other, hitherto less well understood mechanisms, might be at work as well. It is concluded that clustering of foodstuffs is common in food hypersensitivity and that in Sweden this phenomenon mostly is due to the association between birch pollen and some foodstuffs. PMID:6731203

  9. Clustering of foodstuffs in food hypersensitivity. An inquiry study in pollen allergic patients.

    PubMed

    Eriksson, N E

    1984-01-01

    600 pollen allergic patients were questioned about hypersensitivity symptoms from various foodstuffs. The answers regarding one foodstuff were compared with those of other foodstuffs making 780 tables, from which the Spearmen 's correlation coefficients were calculated. Most of the combinations of foodstuffs showed statistically significant correlations. The highest value of the correlation coefficient was found for certain combinations: Various nuts reciprocally as well as nuts combined with apple and stone fruits. Stone fruits reciprocally and even stone fruits combined with apple and pear. Apple and pear. Kiwi fruit and avocado. Potato and carrot. Swede , parsnip and celery reciprocally. Strawberry and wild strawberry. Fish and bread, fish and cheese. Beer and wine. Several of the foodstuffs showing high degrees of correlation are known to be associated with birch pollen allergies. It is probable that at least some of these correlations are due to true IgE-mediated cross-reactivity with common allergens in birch pollen and foodstuffs. Other, hitherto less well understood mechanisms, might be at work as well. It is concluded that clustering of foodstuffs is common in food hypersensitivity and that in Sweden this phenomenon mostly is due to the association between birch pollen and some foodstuffs.

  10. Biomarkers for visceral hypersensitivity identified by classification of electroencephalographic frequency alterations.

    PubMed

    Graversen, Carina; Brock, Christina; Drewes, Asbjørn Mohr; Farina, Dario

    2011-10-01

    Abdominal pain is frequently related to visceral hypersensitivity. This is associated with increased neuronal excitability in the central nervous system (CNS), which can be manifested as discrete electroencephalographic (EEG) alterations. In the current placebo-controlled study, visceral hypersensitivity was evoked by chemical irritation of the esophagus with acid and capsaicin perfusion. The resulting hyperexcitability of the CNS was evaluated by evoked brain potentials following painful electrical stimulations of a remote organ--the rectosigmoid colon. Alterations in individual EEG power distributions between baseline and after perfusion were quantified by extracting features from the evoked brain potentials using an optimized discrete wavelet transform. Visceral hypersensitivity was identified as increased EEG power in the delta, theta and alpha frequency bands. By applying a support vector machine in regression mode, the individual baseline corrected alterations after sensitization were discriminated from alterations caused by placebo perfusions. An accuracy of 91.7% was obtained (P < 0.01). The regression value representing the overall alteration of the EEG correlated with the degree of hyperalgesia (P = 0.03). In conclusion, this study showed that classification of EEG can be used to detect biomarkers reflecting central neuronal changes. In the future, this may be used in studies of pain physiology and pharmacological interventions.

  11. Biomarkers for visceral hypersensitivity identified by classification of electroencephalographic frequency alterations

    NASA Astrophysics Data System (ADS)

    Graversen, Carina; Brock, Christina; Mohr Drewes, Asbjørn; Farina, Dario

    2011-10-01

    Abdominal pain is frequently related to visceral hypersensitivity. This is associated with increased neuronal excitability in the central nervous system (CNS), which can be manifested as discrete electroencephalographic (EEG) alterations. In the current placebo-controlled study, visceral hypersensitivity was evoked by chemical irritation of the esophagus with acid and capsaicin perfusion. The resulting hyperexcitability of the CNS was evaluated by evoked brain potentials following painful electrical stimulations of a remote organ—the rectosigmoid colon. Alterations in individual EEG power distributions between baseline and after perfusion were quantified by extracting features from the evoked brain potentials using an optimized discrete wavelet transform. Visceral hypersensitivity was identified as increased EEG power in the delta, theta and alpha frequency bands. By applying a support vector machine in regression mode, the individual baseline corrected alterations after sensitization were discriminated from alterations caused by placebo perfusions. An accuracy of 91.7% was obtained (P < 0.01). The regression value representing the overall alteration of the EEG correlated with the degree of hyperalgesia (P = 0.03). In conclusion, this study showed that classification of EEG can be used to detect biomarkers reflecting central neuronal changes. In the future, this may be used in studies of pain physiology and pharmacological interventions.

  12. Innovations for combating dentin hypersensitivity: current state of the art.

    PubMed

    Li, Yiming

    2012-06-01

    Dentin hypersensitivity is a common dental complaint, and in severe cases it can impair eating, drinking, and even speaking, thus interfering with the normal daily life of an individual. Throughout years of research, there has been significant advancement in understanding dentin hypersensitivity, and various treatment regimens have been developed for combating the problem. The continued efforts have recently resulted in a novel technology that uses 8% arginine and calcium carbonate for treating dentin hypersensitivity. Formulations of oral care products using this technology--including toothpaste and prophylactic pastes--have demonstrated not only their effectiveness but also their ability to provide instant relief. This paper provides an overview of the etiology of dentin hypersensitivity, the discovery and development of measures for combating the problem, and the available data on the clinical efficacy of products based on 8% arginine and calcium carbonate.

  13. [A patient with paclitaxel hypersensitivity treated with nab-paclitaxel].

    PubMed

    Ouchi, Akira; Ouchi, Akira; Asano, Masahiko; Aono, Keiya; Watanabe, Tetsuya; Kato, Takehiro

    2014-07-01

    A 63-year-old man with multiple liver metastases from gastric cancer was treated with S-1 plus cisplatin; however, the number of multiple liver metastases increased. The patient received paclitaxel(PTX)treatment, but a hypersensitivity reaction occurred after administering the second dose; therefore, he received docetaxel treatment. A hypersensitivity reaction occurred after administering the first dose of docetaxel; therefore, he received irinotecan treatment. However, irinotecan administration was stopped because of severe diarrhea and weight reduction. Subsequently, at the patient's request, nab-PTX treatment was initiated by administering a premedication regimen of dexamethasone(8mg)and chlorpheniramine(10mg); no hypersensitivity reactions were reported thereafter. Nab-PTX is a contraindication; however, it might be possible to use nab-PTX for treating patients with PTX hypersensitivity.

  14. 38 CFR Appendix B to Part 4 - Numerical Index of Disabilities

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Fibrosis of lung, diffuse interstitial. 6826 Desquamative interstitial pneumonitis. 6827 Pulmonary alveolar proteinosis. 6828 Eosinophilic granuloma. 6829 Drug-induced, pneumonitis & fibrosis. 6830 Radiation-induced, pneumonitis & fibrosis. 6831 Hypersensitivity pneumonitis. 6832 Pneumoconiosis. 6833 Asbestosis. Mycotic...

  15. Hypersensitivity associated with sugammadex administration: a systematic review.

    PubMed

    Tsur, A; Kalansky, A

    2014-11-01

    Sugammadex is a drug used to reverse neuromuscular blockade induced by rocuronium or vecuronium. It has not yet been approved by the Food and Drug Administration in the USA due to concerns regarding hypersensitivity. The objective of this review was to identify similarities in the presentation of hypersensitivity reactions to sugammadex. A comprehensive search was performed in PubMed, Scopus and Web of Science for cases reporting hypersensitivity reactions to sugammadex. In addition, we contacted regulatory agencies and the company marketing the drug for unpublished reports. Reports were included if they were in English, primary investigations, lacked an alternative probable explanation for the reaction and included a comprehensive description of the hypersensitivity. We identified 15 cases of hypersensitivity following sugammadex administration. All cases that reported exact timing (14/15) occurred in 4 min or less. Most of the patients (11/15; 73%) met World Anaphylaxis Organization criteria for anaphylaxis. Awareness must be raised for the possibility of drug-induced hypersensitivity during the critical 5-min period immediately following sugammadex administration.

  16. Dentin hypersensitivity: Recent trends in management.

    PubMed

    Miglani, Sanjay; Aggarwal, Vivek; Ahuja, Bhoomika

    2010-10-01

    Dentinal hypersensitivity (DH) is a common clinical condition usually associated with exposed dentinal surfaces. It can affect patients of any age group and most commonly affects the canines and premolars of both the arches. This article concisely reviews the patho-physiology, mechanism and clinical management of the DH. Treatment of DH should start with an accurate diagnosis. Differential diagnosis should be made and all other probable causes should be excluded. An often neglected phase of clinical management of DH is the identification and treatment of the causative factors of DH. By removing the etiological factors, the condition can be even prevented from occurring or recurring. There are various treatment modalities available which can be used at home or may be professionally applied. The "at home" desensitizing agents include toothpastes, mouthwashes or chewing gums and they act by either occluding the dentinal tubules or blocking the neural transmission. This article also discusses the recent treatment options like bioglass, Portland cement, lasers and casein phosphopeptide.

  17. Hypersensitivity to pain in congenital blindness.

    PubMed

    Slimani, Hocine; Danti, Sabrina; Ricciardi, Emiliano; Pietrini, Pietro; Ptito, Maurice; Kupers, Ron

    2013-10-01

    Vision is important for avoiding encounters with objects in the environment that may imperil physical integrity. We tested whether, in the absence of vision, a lower pain threshold would arise from an adaptive shift to other sensory channels. We therefore measured heat and cold pain thresholds and responses to suprathreshold heat stimuli in 2 groups of congenitally blind and matched normal-sighted participants. We also assessed detection thresholds for innocuous warmth and cold, and participants' attitude toward painful encounters in daily life. Our results show that, compared to sighted subjects, congenitally blind subjects have lower heat pain thresholds, rate suprathreshold heat pain stimuli as more painful, and have increased sensitivity for cold pain stimuli. Thresholds for nonpainful thermal stimulation did not differ between groups. The results of the pain questionnaires further indicated that blind subjects are more attentive to signals of external threats. These findings indicate that the absence of vision from birth induces a hypersensitivity to painful stimuli, lending new support to a model of sensory integration of vision and pain processing. PMID:24040972

  18. DELAYED HYPERSENSITIVITY TO HAPTEN-PROTEIN CONJUGATES

    PubMed Central

    Cell, P. G. H.; Silverstein, Arthur M.

    1962-01-01

    Further data have been presented showing that the specificity of the delayed hypersensitivity reaction in the guinea pig to hapten-protein conjugates involves to a considerable degree a contribution by the protein carrier. The carrier contribution is such that sensitization to guinea pig albumin-m-azobenzenesulfonate, for example, does not result in cross-reaction with conjugates of the same hapten with unrelated proteins such as ovalbumin or human gamma globulin, nor were cross-reactions observed between conjugates prepared with the same hapten, coupled to the same protein, but by two different chemical routes, such that the point of attachment of the hapten to the protein differed. It thus appears that in this system both hapten and carrier protein are necessary, but that neither alone is in general sufficient to stimulate the delayed sensitive cell. Desensitization experiments with cross-reacting hapten-protein conjugates have suggested the presence of a multiplicity of antigenic determinants participating in the elicitation of the delayed lesion, and of a concomitant development of a heterogeneity of specificities in the population of delayed sensitive cells in the sensitized animal. The data are discussed in terms of the apparent requirement of the delayed sensitivity mechanism for a larger functional antigenic determinant than that required for interaction with circulating antibodies. Some possible explanations for this difference, and some of its consequences, are discussed. PMID:13897619

  19. Genetic Variation Associated with Hypersensitivity to Mercury

    PubMed Central

    Austin, David William; Spolding, Briana; Gondalia, Shakuntla; Shandley, Kerrie; Palombo, Enzo A.; Knowles, Simon; Walder, Ken

    2014-01-01

    Objectives: Very little is known about mechanisms of idiosyncratic sensitivity to the damaging effects of mercury (Hg); however, there is likely a genetic component. The aim of the present study was to search for genetic variation in genes thought to be involved in Hg metabolism and transport in a group of individuals identified as having elevated Hg sensitivity compared to a normal control group. Materials and Methods: Survivors of pink disease (PD; infantile acrodynia) are a population of clinically identifiable individuals who are Hg sensitive. In the present study, single nucleotide polymorphisms in genes thought to be involved in Hg transport and metabolism were compared across two groups: (i) PD survivors (n = 25); and (ii) age- and sex-matched healthy controls (n = 25). Results: Analyses revealed significant differences between groups in genotype frequencies for rs662 in the gene encoding paraoxanase 1 (PON1) and rs1801131 in the gene encoding methylenetetrahydrofolate reductase (MTHFR). Conclusions: We have identified two genetic polymorphisms associated with increased sensitivity to Hg. Genetic variation in MTHFR and PON1 significantly differentiated a group formerly diagnosed with PD (a condition of Hg hypersensitivity) with age- and gender-matched healthy controls. PMID:25948960

  20. Dentin hypersensitivity: Recent trends in management.

    PubMed

    Miglani, Sanjay; Aggarwal, Vivek; Ahuja, Bhoomika

    2010-10-01

    Dentinal hypersensitivity (DH) is a common clinical condition usually associated with exposed dentinal surfaces. It can affect patients of any age group and most commonly affects the canines and premolars of both the arches. This article concisely reviews the patho-physiology, mechanism and clinical management of the DH. Treatment of DH should start with an accurate diagnosis. Differential diagnosis should be made and all other probable causes should be excluded. An often neglected phase of clinical management of DH is the identification and treatment of the causative factors of DH. By removing the etiological factors, the condition can be even prevented from occurring or recurring. There are various treatment modalities available which can be used at home or may be professionally applied. The "at home" desensitizing agents include toothpastes, mouthwashes or chewing gums and they act by either occluding the dentinal tubules or blocking the neural transmission. This article also discusses the recent treatment options like bioglass, Portland cement, lasers and casein phosphopeptide. PMID:21217949

  1. IgE-mediated food hypersensitivity disorders.

    PubMed

    Gotua, M; Lomidze, N; Dolidze, N; Gotua, T

    2008-04-01

    Food allergy has become a serious health concern especially in developed countries in the past two decades. In general population approximately 4-6% of children and 1-3% of adults experience food allergy. The article reviews IgE-mediated food hypersensitivity disorders. Epidemiology, Mechanism, Clinical manifestations, Genetically modified crops (GMOs), Diagnosis, Prevention and Treatment of IgE-mediated food allergies are discussed. The investigations show that over 90% of IgE-mediated food allergies in childhood are caused by: cow's milk, hen's egg, soy, peanuts, tree nuts, wheat, fish and shellfish. Also the causes of food allergy are food additives, genetically modified crops. Risk factors for food-dependent exercise-induced anaphylaxis include asthma and previous allergic reactions to the causative food. Food allergy is one of the most common causes of systematic anaphylaxis and anaphylactoid reactions, with an annual incidence of four cases per million populations and estimated 500 deaths annually. In addition to gastrointestinal symptoms, individuals may experience urticaria, angioedema, atopic dermatitis, oral syndrome, asthma, rhinitis, conjunctivitis, hypotension, shock and cardiac arrhythmias, caused by the massive release of mediators from mast cells and basophiles. Diagnosis of food allergy is based on history, detailed dietary analysis, skin testing, measuring specific IgE in blood serum and challenge tests. Treatment and prevention includes: avoidance diet, application of auto-injectable epinephrine, H1 and H2 antihistamines, corticosteroids, antileukotrienes, prostaglandin synthetase inhibitors, cromolyn sodium, etc.

  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.

  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. Detection of Mycoplasma ovipneumoniae and Pasteurella haemolytica antigens by an immunoperoxidase technique in pneumonic ovine lungs.

    PubMed

    Haziroglu, R; Diker, K S; Turkarslan, J; Gulbahar, M Y

    1996-01-01

    Four hundred twenty pneumonic lungs from lambs were examined for Mycoplasma ovipneumoniae and Pasteurella haemolytica by an immunoperoxidase technique using an extravidin-biotin-peroxidase complex method in formalin-fixed, paraffin-embedded sections. Histologic examination of tissue sections revealed strong positive reactions in 60.9% and 68.3% of the lungs against M. ovipneumoniae and P. haemolytica, respectively. M. ovipneumoniae and P. haemolytica antigens were observed at the surface and/or within the epithelial cells, macrophages, leucocytes, and bronchiolar exudate. The location of M. ovipneumoniae in the cytoplasm of the epithelial cells and P. haemolytica in the neutrophils was detected immunohistochemically.

  5. 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.

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

    SciTech Connect

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

    2008-11-15

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

  7. Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.

    PubMed

    Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H

    2015-12-01

    Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity. PMID:26454262

  8. Hypersensitivity Responses in the Central Nervous System

    PubMed Central

    Khorooshi, Reza; Asgari, Nasrin; Mørch, Marlene Thorsen; Berg, Carsten Tue; Owens, Trevor

    2015-01-01

    Immune-mediated tissue damage or hypersensitivity can be mediated by autospecific IgG antibodies. Pathology results from activation of complement, and antibody-dependent cellular cytotoxicity, mediated by inflammatory effector leukocytes include macrophages, natural killer cells, and granulocytes. Antibodies and complement have been associated to demyelinating pathology in multiple sclerosis (MS) lesions, where macrophages predominate among infiltrating myeloid cells. Serum-derived autoantibodies with predominant specificity for the astrocyte water channel aquaporin-4 (AQP4) are implicated as inducers of pathology in neuromyelitis optica (NMO), a central nervous system (CNS) demyelinating disease where activated neutrophils infiltrate, unlike in MS. The most widely used model for MS, experimental autoimmune encephalomyelitis, is an autoantigen-immunized disease that can be transferred to naive animals with CD4+ T cells, but not with antibodies. By contrast, NMO-like astrocyte and myelin pathology can be transferred to mice with AQP4–IgG from NMO patients. This is dependent on complement, and does not require T cells. Consistent with clinical observations that interferon-beta is ineffective as a therapy for NMO, NMO-like pathology is significantly reduced in mice lacking the Type I IFN receptor. In MS, there is evidence for intrathecal synthesis of antibodies as well as blood–brain barrier (BBB) breakdown, whereas in NMO, IgG accesses the CNS from blood. Transfer models involve either direct injection of antibody and complement to the CNS, or experimental manipulations to induce BBB breakdown. We here review studies in MS and NMO that elucidate roles for IgG and complement in the induction of BBB breakdown, astrocytopathy, and demyelinating pathology. These studies point to significance of T-independent effector mechanisms in neuroinflammation. PMID:26500654

  9. Hypersensitivity to thrombin of platelets from hypercholesterolemic rats

    SciTech Connect

    Winocour, P.D.; Rand, M.L.; Kinlough-Rathbone, R.L.; Mustard, J.F.

    1986-03-01

    Hypersensitivity of platelets to thrombin has been associated with hypercholesterolemia. The authors have examined the mechanisms involved in this hypersensitivity. Rats were given diets rich in milk fat and containing added cholesterol and taurocholate to produce hypercholesterolemia (HC) (262 +/- 25 mg%) or added sitosterol as a normocholesterolemic control (NC) (89 +/- 6 mg%). Washed platelets were prelabelled with /sup 14/C-serotonin. In the presence of acetylsalicyclic acid (ASA) (to inhibit thromboxane A/sub 2/ (TXA/sub 2/) formation) and creatine phosphate/creatine phosphokinase (CP/CPK) (to remove released ADP), HC platelets aggregated more (26 +/- 1%) and released more /sup 14/C (9.1 +/- 2.0%) than NC platelets (aggregation: 0%, p < 0.001; /sup 14/C release: 1.5 +/- 0.5%, p < 0.002) in response to thrombin (0.075 U/ml). Thus, a pathway independent of released ADP or TXA/sub 2/ formation is involved in the hypersensitivity of HC platelets to thrombin. Total binding of /sup 125/I-thrombin to HC platelets was less than that to NC platelets but HC platelets were smaller and had less protein than NC platelets; the thrombin binding per mg platelet protein was the same for HC and NC platelets, indicating that hypersensitivity to thrombin of HC platelets does not result from increased thrombin binding. Thus, hypersensitivity of HC platelets to thrombin is not due to TXA/sub 2/ formation, the action of released ADP or increased thrombin binding.

  10. Environmental chemicals relevant for respiratory hypersensitivity: the indoor environment.

    PubMed

    Becher, R; Hongslo, J K; Jantunen, M J; Dybing, E

    1996-08-01

    The allergenic constituents of non-industrial indoor environments are predominantly found in the biologic fraction. Several reports have related biological particles such as mites and their excreta, dander from pets and other furred animals, fungi and bacteria to allergic manifestations including respiratory hypersensitivity among the occupants of buildings. Also, bacterial cell-wall components and the spores of toxin-producing moulds may contribute to the induction of hypersensitivity, but the relevance for human health is not yet determined. The knowledge regarding hypersensitivity and asthmatic reactions after exposure to chemical agents is primarily based on data from occupational settings with much higher exposure levels than usually found in non-industrial indoor environments. However, there is evidence that indoor exposure to tobacco smoke, some volatile organic compounds (VOC) and various combustion products (either by using unvented stoves or from outdoor sources) can be related to asthmatic symptoms. In some susceptible individuals, the development of respiratory hypersensitivity or elicitation of asthmatic symptoms may also be related to the indiscriminate use of different household products followed by exposure to compounds such as diisocyanates, organic acid anhydrides, formaldehyde, styrene and hydroquinone. At present, the contribution of the indoor environment both to the development of respiratory hypersensitivity and for triggering asthmatic symptoms is far from elucidated.

  11. Immediate-type hypersensitivity to polyethylene glycols: a review.

    PubMed

    Wenande, E; Garvey, L H

    2016-07-01

    Polyethylene glycols (PEGs) or macrogols are polyether compounds widely used in medical and household products. Although generally considered biologically inert, cases of mild to life-threatening immediate-type PEG hypersensitivity are reported with increasing frequency. Nevertheless, awareness of PEG's allergenic potential remains low, due to a general lack of suspicion towards excipients and insufficient product labelling. Information on immediate-type reactions to PEG is limited to anecdotal reports, and the potential for PEG sensitization and cross-sensitization to PEGylated drugs and structurally related derivatives is likely underestimated. Most healthcare professionals have no knowledge of PEG and thus do not suspect PEG's as culprit agents in hypersensitivity reactions. In consequence, patients are at risk of misdiagnosis and commonly present with a history of repeated, severe reactions to a range of unrelated products in hospital and at home. Increased awareness of PEG prevalence, PEG hypersensitivity, and improved access to PEG allergy testing, should facilitate earlier diagnosis and reduce the risk of inadvertent re-exposure. This first comprehensive review provides practical information for allergists and other healthcare professionals by describing the clinical picture of 37 reported cases of PEG hypersensitivity since 1977, summarizing instances where PEG hypersensitivity should be considered and proposing an algorithm for diagnostic management. PMID:27196817

  12. Total Knee Arthroplasty Failure Induced by Metal Hypersensitivity

    PubMed Central

    Gupta, Ryan; Phan, Duy; Schwarzkopf, Ran

    2015-01-01

    Patient: Female, 70 Final Diagnosis: Metal hypersensitivity Symptoms: Joint pain • swelling • instability Medication: — Clinical Procedure: Revision total knee arthroplasty Specialty: Orthopedics and Traumatology Objective: Unusual clinical course Background: Metal hypersensitivity is an uncommon complication after total knee arthroplasty (TKA) that can lead to significant functional impairment and aseptic prosthesis failure. Case Report: We describe a 70-year-old patient who presented with persistent pain, swelling, and instability 2 years after a primary TKA. The patient had a history of metal hypersensitivity following bilateral metal-on-metal total hip arthroplasty (THA) that was revised to ceramic-on-polyethylene implants. Knee radiographs showed severe osteolysis with implant loosening. Serum cobalt was elevated and serum chromium was significantly elevated, while joint aspiration and inflammatory marker levels ruled out a periprosthetic infection. Revision TKA was performed, with intraoperative tissue pathology and postoperative leukocyte transformation testing confirming metal hypersensitivity as the cause for aseptic implant failure. Conclusions: This case report demonstrates the clinical and laboratory signs that suggest metal hypersensitivity in total knee arthroplasty and the potential for joint function restoration with revision surgery. PMID:26278890

  13. [No hair loss, but colitis or pneumonitis: unique side effects of immune checkpoint inhibitors for cancer].

    PubMed

    Steenbruggen, T G; van den Heuvel, M M; Blank, C U; van Dieren, J M; Haanen, J B A G; Kok, M

    2016-01-01

    Immunotherapy with checkpoint inhibitors is an effective strategy for several cancers. In some patients long-term remissions are seen. However, enhancement of the immune response can be accompanied by immune-related adverse events (irAEs). These patients often present with nonspecific symptoms. The most common irAEs are dermatitis, colitis, pneumonitis, hepatitis and endocrinopathies. IrAEs can occur in every organ, even simultaneously. Furthermore, irAEs can occur weeks or months after discontinuation of checkpoint inhibitors. Most irAEs can be well managed, but life-threatening situations do occur. General management involves supportive care, glucocorticoids and sometimes immunomodulatory drugs, such as infliximab. Early diagnosis and adequate team management can improve the course of irAEs without compromising the cancer treatment. Here, we present two cases: a melanoma patient with an ipilimumab-induced colitis and a lung cancer patient with pneumonitis after anti-PD-1.We then summarise the most common toxicities of checkpoint inhibitors, emphasising the need to familiarise the practitioner with irAEs of approved and emerging immunotherapies.

  14. [No hair loss, but colitis or pneumonitis: unique side effects of immune checkpoint inhibitors for cancer].

    PubMed

    Steenbruggen, T G; van den Heuvel, M M; Blank, C U; van Dieren, J M; Haanen, J B A G; Kok, M

    2016-01-01

    Immunotherapy with checkpoint inhibitors is an effective strategy for several cancers. In some patients long-term remissions are seen. However, enhancement of the immune response can be accompanied by immune-related adverse events (irAEs). These patients often present with nonspecific symptoms. The most common irAEs are dermatitis, colitis, pneumonitis, hepatitis and endocrinopathies. IrAEs can occur in every organ, even simultaneously. Furthermore, irAEs can occur weeks or months after discontinuation of checkpoint inhibitors. Most irAEs can be well managed, but life-threatening situations do occur. General management involves supportive care, glucocorticoids and sometimes immunomodulatory drugs, such as infliximab. Early diagnosis and adequate team management can improve the course of irAEs without compromising the cancer treatment. Here, we present two cases: a melanoma patient with an ipilimumab-induced colitis and a lung cancer patient with pneumonitis after anti-PD-1.We then summarise the most common toxicities of checkpoint inhibitors, emphasising the need to familiarise the practitioner with irAEs of approved and emerging immunotherapies. PMID:27438388

  15. Experimental radiation pneumonitis. Corticosteroids increase the replicative activity of alveolar type 2 cells

    SciTech Connect

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

    1988-09-01

    Corticosteroid administration during radiation pneumonitis in mice markedly improves the physiologic abnormalities and decreases mortality, an effect that has been attributed to the stimulation of surfactant synthesis and secretion by type 2 alveolar epithelial cells. In the present experiments we explored the effects of corticosteroids on the replicative activity of type 2 cells of lethally irradiated lungs at the height of the radiation reaction. The labeling index of type 2 cells of irradiated mice was increased threefold above that of sham-irradiated controls. Corticosteroids given continuously from 10 weeks after thoracic irradiation further increased the type 2 cell labeling index another threefold above that of irradiated untreated mice. The enhanced reproductive activity of type 2 cells following thoracic irradiation is seen as a protective response that is augmented by corticosteroids, whose effect may be both to improve the physiology of the alveolar surface and to maintain the population of alveolar epithelial cells. The bearing of this result on the controversial role of the type 2 cell as a target in radiation pneumonitis is discussed.

  16. Feed exposure to FB1 can aggravate pneumonic damages in pigs provoked by P. multocida.

    PubMed

    Kovács, Melinda; Pósa, Roland; Tuboly, Tamás; Donkó, Tamás; Repa, Imre; Tossenberger, János; Szabó-Fodor, Judit; Stoev, Stoycho; Magyar, Tibor

    2016-10-01

    The possible interaction between Pasteurella multocida and the mycotoxin fumonisin B1 (FB1), recognised as one of the most often food/feed contaminant, was studied with the aim to evaluate whether and how FB1 can influence and/or complicate the development and severity of various pathological damages provoked by Pasteurella multocida in some internal organs of pigs. Heavier lung pathology was seen in pigs experimentally infected with Pasteurella multocida, when the same were exposed to 20ppm dietary levels of fumonisin B1 (FB1) as was assessed by gross pathology, pathomorphological examinations, clinical biochemistry and some immunological investigations. The most typical damages in FB1 treated pigs were the strong oedema in the lung and the slight oedema in the other internal organs and mild degenerative changes in the kidneys, whereas the typical pathomorphological findings in pigs infected with Pasteurella multocida was broncho-interstitial pneumonia. FB1 was found to aggravate pneumonic changes provoked by P. multocida in the cranial lobes of the lung and to complicate pneumonic damages with interstitial oedema in the lung. No macroscopic damages were observed in the pigs infected only with Pasteurella multocida. It can be concluded that the feed intake of FB1 in pigs may complicate or exacerbate the course of P. multocida serotype A infection. PMID:27663368

  17. Impact of the Pla Protease Substrate α2-Antiplasmin on the Progression of Primary Pneumonic Plague

    PubMed Central

    Eddy, Justin L.; Schroeder, Jay A.; Zimbler, Daniel L.; Bellows, Lauren E.

    2015-01-01

    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

  18. [Human plague and pneumonic plague : pathogenicity, epidemiology, clinical presentations and therapy].

    PubMed

    Riehm, Julia M; Löscher, Thomas

    2015-07-01

    Yersinia pestis is a highly pathogenic gram-negative bacterium and the causative agent of human plague. In the last 1500 years and during three dreaded pandemics, millions of people became victims of Justinian's plague, the Black Death, or modern plague. Today, Y. pestis is endemic in natural foci of Asian, African and American countries. Due to its broad dissemination in mammal species and fleas, eradication of the pathogen will not be possible in the near future. In fact, plague is currently classified as a "re-emerging disease". Infection may occur after the bite of an infected flea, but also after oral ingestion or inhalation of the pathogen. The clinical presentations comprise the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Most human cases can successfully be treated with antibiotics. However, the high transmission rate and lethality of pneumonic plague require international and mandatory case notification and quarantine of patients. Rapid diagnosis, therapy and barrier nursing are not only crucial for the individual patient but also for the prevention of further spread of the pathogen or of epidemics. Therefore, WHO emergency schedules demand the isolation of cases, identification and surveillance of contacts as well as control of zoonotic reservoir animals and vectors. These sanctions and effective antibiotic treatment usually allow a rapid containment of outbreaks. However, multiple antibiotic resistant strains of Y. pestis have been isolated from patients in the past. So far, no outbreaks with such strains have been reported.

  19. Necrotizing meningoencephalitis and pneumonitis in a simian immunodeficiency virus-infected rhesus macaque due to Acanthamoeba.

    PubMed

    Westmoreland, S V; Rosen, J; MacKey, J; Romsey, C; Xia, D-L; Visvesvera, G S; Mansfield, K G

    2004-07-01

    Free-living amoebae of the genus Acanthamoeba can cause a fatal disease of the brain in humans called granulomatous amoebic encephalitis. We present a case of meningoencephalitis and pneumonitis in a simian immunodeficiency virus (SIV)-infected rhesus macaque caused by Acanthamoeba sp. The animal became ill 176 days after intravenous inoculation with SIVmac251 after a short history of weight loss and a sudden onset of hind limb paresis and abnormal head movements. Histopathologic examination of hematoxylin and eosin-stained tissues revealed multifocal to coalescing necrotizing neutrophilic meningoencephalitis and pneumonitis. Immunofluorescence and polymerase chain reaction were used to identify the genus of amoeba as Acanthamoeba. Immunohistochemistry of immune cell markers was used to characterize the animal's immune response to the opportunistic amoebic infection with features of both innate and adaptive cell-mediated immunity. Although not previously reported, the potential transmission to humans, either through environmental contamination or contact with an infected animal, makes this disease a threat to laboratory animal care staff and pathologists. PMID:15232140

  20. 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.

  1. 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

  2. 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.

  3. Feed exposure to FB1 can aggravate pneumonic damages in pigs provoked by P. multocida.

    PubMed

    Kovács, Melinda; Pósa, Roland; Tuboly, Tamás; Donkó, Tamás; Repa, Imre; Tossenberger, János; Szabó-Fodor, Judit; Stoev, Stoycho; Magyar, Tibor

    2016-10-01

    The possible interaction between Pasteurella multocida and the mycotoxin fumonisin B1 (FB1), recognised as one of the most often food/feed contaminant, was studied with the aim to evaluate whether and how FB1 can influence and/or complicate the development and severity of various pathological damages provoked by Pasteurella multocida in some internal organs of pigs. Heavier lung pathology was seen in pigs experimentally infected with Pasteurella multocida, when the same were exposed to 20ppm dietary levels of fumonisin B1 (FB1) as was assessed by gross pathology, pathomorphological examinations, clinical biochemistry and some immunological investigations. The most typical damages in FB1 treated pigs were the strong oedema in the lung and the slight oedema in the other internal organs and mild degenerative changes in the kidneys, whereas the typical pathomorphological findings in pigs infected with Pasteurella multocida was broncho-interstitial pneumonia. FB1 was found to aggravate pneumonic changes provoked by P. multocida in the cranial lobes of the lung and to complicate pneumonic damages with interstitial oedema in the lung. No macroscopic damages were observed in the pigs infected only with Pasteurella multocida. It can be concluded that the feed intake of FB1 in pigs may complicate or exacerbate the course of P. multocida serotype A infection.

  4. Management of hypersensitivity reactions to anti-D immunoglobulin preparations.

    PubMed

    Rutkowski, K; Nasser, S M

    2014-11-01

    RhD immunoglobulin G (anti-D) administered to pregnant Rh(-) women prevents Rh isoimmunization. Its use has significantly reduced the incidence of haemolytic disease of the foetus and newborn previously responsible for one death in every 2200 births. In pregnancy, acute drug-induced hypersensitivity reactions including anaphylaxis can have serious deleterious effects on the mother and foetus/neonate. Women can be erroneously labelled as drug allergic as the investigation of hypersensitivity reactions in pregnancy is complex and drug challenges are usually contraindicated. We present three cases of suspected anti-D hypersensitivity clinically presenting as anaphylaxis and delayed transfusion-related reaction. We also propose a new algorithm for the investigations of such reaction. It relies on detailed history, cautious interpretation of skin tests, foetal Rh genotyping from maternal blood and, in some cases, anti-D challenges. This is not to deprive women of anti-D which might put their future pregnancies at risk. PMID:25066207

  5. Contact hypersensitivity response to isophorone diisocyanate in mice

    SciTech Connect

    Stern, M.L.; Brown, T.A.; Brown, R.D.; Munson, A.E. )

    1989-09-01

    Isophorone diisocyanate was evaluated for its potential as a sensitizing agent for allergic contact hypersensitivity in mice. Female B6C3F1 mice were sensitized with 0.1, 0.3, and 1.0% isophorone diisocyanate and challenged with 3.0% isophorone diisocyanate. Doses of isophorone diisocyanate were selected from assays for primary irritancy. Mice received 20 microliters by direct dermal application, for 5 days, to sites prepared by shaving, dermabrading and, in some mice, with intra dermal injection of complete Freund's adjuvant. The rest period was 7 days. Measurement of the contact hypersensitivity response in mice was by radioisotopic assay two days after challenge and mouse ear swelling one and two days after challenge. Mice demonstrated statistically significant dose-dependent contact hypersensitivity responses to isophorone diisocyanate with or without adjuvant pretreatment.

  6. Dentin Hypersensitivity: Etiology, Diagnosis and Treatment; A Literature Review

    PubMed Central

    Davari, AR; Ataei, E; Assarzadeh, H

    2013-01-01

    The objective of this review is to inform practitioners about dentin hypersensitivity (DH); to provide a brief overview of the diagnosis, etiology and clinical management of dentin hypersensitivity and to discuss technical approaches to relieve sensitivity. This clinical information is described in the context of the underlying biology. The author used PUBMED to find relevant English-language literature published in the period 1999 to 2010. The author used combinations of the search terms “dentin*”, “tooth”, “teeth”, “hypersensit*”, “desensitiz*”. Abstracts and also full text articles to identify studies describing etiology, prevalence, clinical features, controlled clinical trials of treatments and relevant laboratory research on mechanisms of action were used. PMID:24724135

  7. Functional dyspepsia: the role of visceral hypersensitivity in its pathogenesis.

    PubMed

    Keohane, John; Quigley, Eamonn M M

    2006-05-01

    Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.

  8. Transmission electron microscopic characterization of hypersensitive human radicular dentin

    SciTech Connect

    Yoshiyama, M.; Noiri, Y.; Ozaki, K.; Uchida, A.; Ishikawa, Y.; Ishida, H. )

    1990-06-01

    Transmission electron microscopy (TEM) and x-ray microanalysis (XMA) were used for the study of the ultrastructure of the lumens of dentinal tubules in superficial layers of dentin specimens obtained by use of a new biopsy technique from both hypersensitive and naturally desensitized areas of exposed root surfaces, in vivo. The TEM images showed clearly that the lumens of most of the tubules were occluded with mineral crystals in naturally desensitized areas, but such lumens were empty and surrounded with peritubular and intertubular dentin in hypersensitive areas. Moreover, electron-dense structures that lined peritubular dentin were observed in the empty lumens of dentinal tubules.

  9. Hypersensitivity reactions to radiocontrast media: the role of complement activation.

    PubMed

    Szebeni, Janos

    2004-01-01

    Although intravenous use of radiocontrast media (RCM) for a variety of radiographic procedures is generally safe, clinically significant acute hypersensitivity reactions still occur in a significant percentage of patients. The mechanism of these anaphylactoid, or "pseudoallergic," reactions is complex, involving complement activation, direct degranulation of mast cells and basophils, and modulation of enzymes and proteolytic cascades in plasma. In this review, basic information on different RCMs and their reactogenicity is summarized and updated, and the prevalence, pathomechanism, prediction, prevention, treatment, and economic impact of hypersensitivity reactions are discussed. Particular attention is paid to the in vitro and in vivo evidence supporting complement activation as an underlying cause of RCM reactions.

  10. Immediate-type latex hypersensitivity in a hairdresser.

    PubMed

    Sajjachareonpong, Praneet; Lee, Adriene; Nixon, Rosemary

    2002-05-01

    Hairdressers commonly develop contact dermatitis caused by either skin irritants or allergens to which they are exposed. Those using latex gloves are also at risk of developing immediate hypersensitivity reactions to latex. We present a hairdresser with hand dermatitis, primarily as a result of immediate-type hypersensitivity to latex causing contact urticaria, diagnosed with radioallergosorbent testing. Only three previous studies have reported latex allergy in hairdressers. This condition needs to be considered as a differential diagnosis in hairdressers presenting with hand dermatitis and a history of wearing either rubber or disposable latex gloves. PMID:11982576

  11. Problem gamblers exhibit reward hypersensitivity in medial frontal cortex during gambling.

    PubMed

    Oberg, Scott A K; Christie, Gregory J; Tata, Matthew S

    2011-11-01

    Problem gambling (PG) is increasingly conceptualized as an addiction akin to substance abuse, rather than an impulse control disorder, however the mechanism of addiction remains unclear. Neuroimaging investigations have supported a "reward deficiency" hypothesis for PG by suggesting a blunted response to gambling, particularly in the striatum. Here we describe electrophysiological evidence of a hypersensitive response to gambling feedback in problem gamblers. Previous research in healthy participants has shown that feedback during gambling tasks triggers stereotypical neural responses including the Feedback-Related Mediofrontal Negativity (FRN), the feedback-related P300, and an increase in induced theta-band (4-8 Hz) power. We tested the theory that abnormal feedback processing characterizes brain activity in problem gamblers while gambling. EEG was recorded from non-gamblers and self-identified gamblers as they engaged in a computerized version of the Iowa Gambling Task. Feedback about valence (win vs. loss) triggered a FRN in both groups, but in gamblers this was preceded by an early-latency hypersensitive fronto-central difference to feedback. This early FRN was correlated with gambling severity and was localized to medial frontal cortex using distributed source imaging (CLARA). Gamblers also differed in responses to risk, showing a blunted P300 component and less EEG power in the theta band. Here we suggest that a more nuanced interpretation of reward deficiency is called for with respect to PG. For certain aspects of brain function, gamblers may exhibit hypersensitivity to reward feedback more akin to drug sensitization than reward deficiency. Our results also suggest that the neurologically normal brain employs dissociable systems in the processing of feedback from tasks involving risky decision making.

  12. Noise-induced Hypersensitivity and Stochastic Resonance: Can Living Systems Use Them at a Molecular Level?

    NASA Astrophysics Data System (ADS)

    Gerashchenko, O. V.; Ginzburg, S. L.; Pustovoit, M. A.

    2003-05-01

    Living organisms are known to receive and transduce useful signals in a very noisy environment. A natural question whether they can use this noise constructively is still lacking solid answer. Some recent works demonstrated that one of the phenomena where noise plays a constructive role, the stochastic resonance (SR), occurs in biology at system and cellular levels of organization. Its existence at molecular level, in ionic channels of cell membranes, is now a subject for intensive, though mainly theoretical, studies. In the present work we study a simple two-state model of ionic channel together with its continuous equivalent, the asymmetrical Kramers oscillator, with external periodic signal and dichotomous external noise. We found that the new kind of SR appears for adiabatically slow external noise, when its amplitude becomes equal to static bias, thus dynamically recovering the system symmetry. These findings are confirmed with analog circuit simulations. The next promising effect is the noise-induced hypersensitivity to small signals. The phenomenon arises in stochastic systems with on-off intermittency. Such a system at optimal external noise intensity and correlation time becomes sensitive to an ultrasmall signal, amplifying it by many orders of magnitude. Such a hypersensitivity is often robust to additive thermal noise. We speculate that a similar effect might occur in various sensory systems that are known to be very noisy and to display unique sensitivity to environmental signals. A simple model system of two neurons with common strong noise source is hypersensitive to small differential signal only in the ideal case of absence of internal noise.

  13. 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

  14. 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) ...

  15. 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 ...

  16. [Allopurinol-induced hypersensitivity syndrome resulting in death].

    PubMed

    Laurisch, Sören; Jaedtke, Maren; Demir, Reyhan; Sorrentino, Sajoscha A; Kielstein, Jan T; Rennekampff, Hans-Oliver; Vogt, Peter M; Meyer, Gerd P; Fuchs, Martin; Klein, Gunnar; Drexler, Hartmut; Schieffer, Bernhard; Napp, L Christian

    2010-04-01

    The present report describes the case of a 67-year-old patient who developed an allopurinol-induced hypersensitivity syndrome (AHS) with toxic epidermal necrolysis and subsequently died of septic multiorgan failure. Considering the increasing prescription rate of allopurinol, the present case report intends to demonstrate the underestimated threat of AHS.

  17. Ant allergens and hypersensitivity reactions in response to ant stings.

    PubMed

    Potiwat, Rutcharin; Sitcharungsi, Raweerat

    2015-12-01

    Hypersensitivity reactions caused by ant stings are increasingly recognized as an important cause of death by anaphylaxis. Only some species of ants ( e.g. Solenopsis spp., Myrmecia spp., and Pachycondyla spp.) cause allergic reactions. Ant species are identified by evaluating the morphologic structures of worker ants or by molecular techniques. Ant venom contains substances, including acids and alkaloids, that cause toxic reactions, and those from Solenopsis invicta or the imported fire ant have been widely studied. Piperidine alkaloids and low protein contents can cause local reactions (sterile pustules) and systemic reactions (anaphylaxis). Imported fire ant venoms are cross-reactive; for example, the Sol i 1 allergen from S. invicta has cross-reactivity with yellow jacket phospholipase. The Sol i 3 allergen is a member of the antigen 5 family that has amino acid sequence identity with vespid antigen 5. The clinical presentations of ant hypersensitivity are categorized into immediate and delayed reactions: immediate reactions, such as small local reactions, large local reactions, and systemic reactions, occur within 1-4 hours after the ant stings, whereas delayed reactions, such as serum sickness and vasculitis, usually occur more than 4 hours after the stings. Tools for the diagnosis of ant hypersensitivity are skin testing, serum specific IgE, and sting challenge tests. Management of ant hypersensitivity can be divided into immediate (epinephrine, corticosteroids), symptomatic (antihistamines, bronchodilators), supportive (fluid resuscitation, oxygen therapy), and preventive (re-sting avoidance and immunotherapy) treatments.

  18. Auditory Hypersensitivity in Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Lucker, Jay R.

    2013-01-01

    A review of records was completed to determine whether children with auditory hypersensitivities have difficulty tolerating loud sounds due to auditory-system factors or some other factors not directly involving the auditory system. Records of 150 children identified as not meeting autism spectrum disorders (ASD) criteria and another 50 meeting…

  19. Ant allergens and hypersensitivity reactions in response to ant stings.

    PubMed

    Potiwat, Rutcharin; Sitcharungsi, Raweerat

    2015-12-01

    Hypersensitivity reactions caused by ant stings are increasingly recognized as an important cause of death by anaphylaxis. Only some species of ants ( e.g. Solenopsis spp., Myrmecia spp., and Pachycondyla spp.) cause allergic reactions. Ant species are identified by evaluating the morphologic structures of worker ants or by molecular techniques. Ant venom contains substances, including acids and alkaloids, that cause toxic reactions, and those from Solenopsis invicta or the imported fire ant have been widely studied. Piperidine alkaloids and low protein contents can cause local reactions (sterile pustules) and systemic reactions (anaphylaxis). Imported fire ant venoms are cross-reactive; for example, the Sol i 1 allergen from S. invicta has cross-reactivity with yellow jacket phospholipase. The Sol i 3 allergen is a member of the antigen 5 family that has amino acid sequence identity with vespid antigen 5. The clinical presentations of ant hypersensitivity are categorized into immediate and delayed reactions: immediate reactions, such as small local reactions, large local reactions, and systemic reactions, occur within 1-4 hours after the ant stings, whereas delayed reactions, such as serum sickness and vasculitis, usually occur more than 4 hours after the stings. Tools for the diagnosis of ant hypersensitivity are skin testing, serum specific IgE, and sting challenge tests. Management of ant hypersensitivity can be divided into immediate (epinephrine, corticosteroids), symptomatic (antihistamines, bronchodilators), supportive (fluid resuscitation, oxygen therapy), and preventive (re-sting avoidance and immunotherapy) treatments. PMID:26708389

  20. 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

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

    PubMed

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

    2015-12-01

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

  2. Efficacy of recombinant leukotoxin in protection against pneumonic challenge with live Pasteurella haemolytica A1.

    PubMed Central

    Conlon, J A; Shewen, P E; Lo, R Y

    1991-01-01

    The recombinant leukotoxin (rLKT) of the bacterium Pasteurella haemolytica A1 was examined for its ability to protect cattle from experimental challenge with logarithmic-phase P. haemolytica. Six different vaccines were utilized in the experiment: P. haemolytica culture supernatant, P. haemolytica culture supernatant enriched with rLKT, rLKT alone, P. haemolytica culture supernatant enriched with Escherichia coli supernatant not containing LKT, E. coli supernatant alone, and phosphate-buffered saline. rLKT alone showed no protective capacity against development of clinical signs of respiratory disease or against development of postmortem lung lesions after experimental challenge. It was, however, shown to enhance the efficacy of the culture supernatant vaccine and decrease clinical signs and pneumonic lesions. The complexity of protective immunity in this disease is emphasized in this study, and, although LKT is an important virulence factor of the organism, an immune response to LKT alone does not protect animals against disease. PMID:1987075

  3. Estrogen-dependent visceral hypersensitivity following stress in rats

    PubMed Central

    Hubbard, Catherine S; Karpowicz, Jane M; Furman, Andrew J; da Silva, Joyce Teixeira; Traub, Richard J

    2016-01-01

    We used functional MRI and a longitudinal design to investigate the brain mechanisms in a previously reported estrogen-dependent visceral hypersensitivity model. We hypothesized that noxious visceral stimulation would be associated with activation of the insula, anterior cingulate cortex, and amygdala, and that estrogen-dependent, stress-induced visceral hypersensitivity would both enhance activation of these regions and recruit activation of other brain areas mediating affect and reward processing. Ovariectomized rats were treated with estrogen (17 β-estradiol, E2) or vehicle (n = 5 per group) and scanned in a 7T MRI at three different time points: pre-stress (baseline), 2 days post-stress, and 18 days post-stress. Stress was induced via a forced-swim paradigm. In a separate group of ovariectomized rats, E2 treatment induced visceral hypersensitivity at the 2 days post-stress time point, and this hypersensitivity returned to baseline at the 18 days post-stress time point. Vehicle-treated rats show no hypersensitivity following stress. During the MRI scans, rats were exposed to noxious colorectal distention. Across groups and time points, noxious visceral stimulation led to activations in the insula, anterior cingulate, and left amygdala, parabrachial nuclei, and cerebellum. A group-by-time interaction was seen in the right amygdala, ventral striatum-pallidum, cerebellum, hippocampus, mediodorsal thalamus, and pontine nuclei. Closer inspection of the data revealed that vehicle-treated rats showed consistent activations and deactivations across time, whereas estrogen-treated animals showed minimal deactivation with noxious visceral stimulation. This unexpected finding suggests that E2 may dramatically alter visceral nociceptive processing in the brain following an acute stressor. This study is the first to examine estrogen-stress dependent interactions in response to noxious visceral stimulation using functional MRI. Future studies that include other control

  4. Pharmacogenetic determinants of immediate and delayed reactions of drug hypersensitivity.

    PubMed

    Guéant, J L; Guéant-Rodriguez, R M; Gastin, I Aimone; Cornejo-García, J A; Viola, M; Barbaud, A; Mertes, P M; Blanca, M; Romano, A

    2008-01-01

    Drug allergy refers to a hypersensitivity reaction for which either an IgE or T-cell-mediated mechanism is demonstrated. The recognition of the drug by B and T cells is influenced by variants of HLA genes. The genetic factors involved in IgE-mediated mechanisms have been studied mainly in beta-lactam reactions, and they appear to be related to human leukocyte antigen presentation (HLA A2 and DRw52), TNFA -308G>A, class switching to IgE by B cells (variants of IL-13 and of IL-4RA), and expression of IgE receptors on target cells (variant of the FcepsilonRIbeta gene). Delayed T-cell-mediated reactions are also associated with HLA alleles. Studies have reported an association of HLA-B*1502 and HLA-B*5801 in patients with the Stevens-Johnson syndrome or toxic epidermal necrolysis provoked by carbamazepine, as well as of HLA-B*5701 with abacavir hypersensitivity. HLA-B*5701 seems to be a strong predictor in whites, but not in Hispanics or Africans. Carbamazepine hypersensitivity is also influenced by gene variants of cytochrome P450 enzymes on the generation of reactive metabolites, while CYP2C9*2 and CYP2C9*3 polymorphisms influence the bioactivation of sulfamethoxazole in prohapten. Pharmacogenetic studies on aspirin hypersensitivity have identified distinct types of predictors, such as HLA genotypes, a polymorphism in the promoter of the FcepsilonRIalpha gene, and variants in genes of enzymes from the arachidonic acid pathway. In the future, identification of genetic predictors will benefit from genomewide association studies that also take ethnic differences into account. Ideally, predictors will help to prevent adverse reactions, as suggested by a recent study on the effectiveness of prospective HLA-B*5701 screening to prevent hypersensitivity reactions to abacavir in HIV patients. PMID:18991696

  5. Antigenic specificities of delayed hypersensitivity in mice to dinitrophenylated proteins

    PubMed Central

    Yonemasu, K.; Crowle, A. J.

    1973-01-01

    Humoral antibodies capable of suppressing induction of delayed hypersensitivity to dinitrophenylated proteins in mice were tested for specific absorbability onto chemically insolubilized antigen and for the antigenic determinant specificities of their immunosuppressive (i.e. contrasensitizing) effects. The activity of an antiserum could be completely removed by absorption with homologous antigen, and it could be recovered by dissociating the absorbed antibodies at low pH and high salt concentration. The immunosuppressive antibodies therefore are specific for determinants on the native antigen, and non-antibody serum constituents are non-essential. By selective immunoabsorptions and elutions, antibodies specific for carrier protein, for dinitrophenyl hapten, and for new determinants unique to the hapten—protein complexes were prepared and were compared with unfractionated antiserum for contrasensitizing activity. Nearly all activity could be accounted for by the anti-hapten antibodies, although anti-carrier antibodies also had some. Despite this evidence that immunosuppressiveness was hapten-specific, the delayed hypersensitivity being suppressed by these antibodies was shown to be directed against hapten—carrier complexes or against carrier but not against hapten alone. Hence, humoral antibodies against a portion of an antigen molecule can suppress induction of delayed hypersensitivity specific for other sometimes unrelated parts of this same molecule, and it is possible to induce antibody-mediated tolerance to a multi-determinant antigen with an antibody response against just a part of the antigen. The theoretical and practical implications of these findings are discussed. Notable theoretically is the observation that although determinant specificities of humoral antibody and delayed hypersensitivity responses to one antigen usually differ, the former can regulate the latter for a given species of antigen molecule. Most important practically is the implication

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

    PubMed

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

    2015-05-01

    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

  7. Hyperacusis Questionnaire as a Tool for Measuring Hypersensitivity to Sound in a Tinnitus Research Population

    PubMed Central

    Fackrell, Kathryn; Fearnley, Constance; Hoare, Derek J.; Sereda, Magdalena

    2015-01-01

    Hypersensitivity to external sounds is often comorbid with tinnitus and may be significant for adherence to certain types of tinnitus management. Therefore, a clear measure of sensitivity to sound is important. The aim of this study was to evaluate the validity and reliability of the Hyperacusis Questionnaire (HQ) for use as a measurement tool using data from a sample of 264 adults who took part in tinnitus research. We evaluated the HQ factor structure, internal consistency, convergent and discriminant validity, and floor and ceiling effects. Internal consistency was high (Cronbach's alpha = 0.88) and moderate correlations were observed between the HQ, uncomfortable loudness levels, and other health questionnaires. Confirmatory factor analysis revealed that the original HQ three-factor solution and a one-factor solution were both a poor fit to the data. Four problematic items were removed and exploratory factor analysis identified a two-factor (attentional and social) solution. The original three-factor structure of the HQ was not confirmed. All fourteen items do not accurately assess hypersensitivity to sound in a tinnitus population. We propose a 10-item (2-factor) version of the HQ, which will need to be confirmed using a new tinnitus and perhaps nontinnitus population. PMID:26557658

  8. Delayed-type hypersensitivity responses in infected mice elicited by cytoplasmic fractions of Cryptococcus neoformans.

    PubMed Central

    Hay, R J; Reiss, E

    1978-01-01

    Four subcellular fractions of Cryptococcus neoformans prepared by differential centrifugation of disrupted whole yeast and a 3-day culture filtrate were examined for their ability to elicit delayed-type hypersensitivity in sensitized animals. The methods used to detect sensitization were (i) the footpad swelling test and inhibition of peritoneal macrophage migration in mice and (ii) skin testing in guinea pigs. Two entities, the post-mitochondrial supernatant and the culture filtrate, showed considerable activity in the footpad test, with 26- and 30-microliter 24-h swellings, respectively, at 6 weeks after infection. With the latter there was interference from a strong antibody-mediated 4-h skin reaction. The post-mitochondrial supernatant produced strong delayed-type hypersensitivity in guinea pigs at a dose of 69 microgram, and there was no demonstrable cross-reactivity in animals sensitized with heterologous fungi. The footpad swelling in mice correlated well with the macrophage migration inhibition test, with 71% inhibition in mice infected subcutaneously with C. neoformans at 6 weeks. However, mice infected intravenously developed poorer cell-mediated immunity than the subcutaneously infected mice. The post-mitochondrial supernatant was found to contain detectable amounts of cryptococcal capsular polysaccharide. Images PMID:365751

  9. 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

  10. Immediate and Delayed Hypersensitivity Reactions to Proton Pump Inhibitors: Evaluation and Management.

    PubMed

    Otani, Iris M; Banerji, Aleena

    2016-03-01

    PPIs are among the most commonly administered medications in the USA and are generally well tolerated. Immediate and delayed immune-mediated hypersensitivity reactions are rare but increasingly recognized adverse effects of proton pump inhibitors (PPIs). Immediate hypersensitivity reactions can occur due to IgE-mediated hypersensitivity to PPIs and can be evaluated by immediate hypersensitivity skin testing and oral provocation challenge testing. A desensitization protocol can be used when PPI use cannot be avoided in an allergic patient. Delayed hypersensitivity reactions to PPIs have also been reported. Occupational exposures causing cutaneous reactions to PPIs are the most commonly reported delayed hypersensitivity reaction, followed by drug-induced subacute cutaneous lupus erythematosus. This review presents a summary of the clinical presentation, diagnostic evaluation, and management of immune-mediated hypersensitivity reactions to PPIs.

  11. Yersinia pestis activates both IL-1β and IL-1 receptor antagonist to modulate lung inflammation during pneumonic plague.

    PubMed

    Sivaraman, Vijay; Pechous, Roger D; Stasulli, Nikolas M; Eichelberger, Kara R; Miao, Edward A; Goldman, William E

    2015-03-01

    Pneumonic plague is the most rapid and lethal form of Yersinia pestis infection. Increasing evidence suggests that Y. pestis employs multiple levels of innate immune evasion and/or suppression to produce an early "pre-inflammatory" phase of pulmonary infection, after which the disease is highly inflammatory in the lung and 100% fatal. In this study, we show that IL-1β/IL-18 cytokine activation occurs early after bacteria enter the lung, and this activation eventually contributes to pulmonary inflammation and pathology during the later stages of infection. However, the inflammatory effects of IL-1β/IL-1-receptor ligation are not observed during this first stage of pneumonic plague. We show that Y. pestis also activates the induction of IL-1 receptor antagonist (IL-1RA), and this activation likely contributes to the ability of Y. pestis to establish the initial pre-inflammatory phase of disease.

  12. A possible prevention strategy of radiation pneumonitis: Combine radiotherapy with aerosol inhalation of hydrogen-rich solution

    PubMed Central

    Chuai, Yunhai; Zhao, Luqian; Ni, Jin; Sun, Ding; Cui, Jianguo; Li, Bailong; Qian, Liren; Gao, Fu; Cai, Jianming

    2011-01-01

    Summary Radiotherapy is an important modality of cancer treatment. Radiation pneumonitis is a major obstacle to increasing the radiation dose in radiotherapy, and it is important to prevent this radiation-induced complication. Recent studies show that hydrogen has a potential as an effective and safe radioprotective agent by selectively reducing hydroxyl and peroxynitrite radicals. Since most of the ionizing radiation-induced cellular damage is caused by hydroxyl radicals, we hypothesize that a treatment combining radiotherapy with aerosol inhalation of a hydrogen-rich solution may be an effective and novel prevention strategy for radiation pneumonitis (hydrogen is explosive, while a hydrogen-rich solution such as physiological saline saturated with molecular hydrogen is safer). PMID:21455114

  13. Combined acute interstitial pneumonitis and pancytopenia induced by low-dose methotrexate in a hemodialysis patient treated for bullous pemphigoid.

    PubMed

    Liu, Haibo; Liu, Fang; Zhang, Min; Yan, Wenliang; Sang, Hong

    2015-01-01

    Methotrexate has been widely used for many years in the treatment of a variety of diseases. Acute pneumonitis and bone marrow suppression are very serious side effects in methotrexate treatment. A 48-year-old man with end-stage renal disease undergoing chronic hemodialysis developed combined acute pneumonitis and pancytopenia after a cumulative dose of 20 mg methotrexate for bullous pemphigoid. Continuous renal replacement therapy (CRRT) can efficiently decrease serum methotrexate concentration. A rapid improvement of clinical symptoms and resolution of pulmonary opacification were found after CRRT. Blood cell counts returned to normal after component blood transfusion and cytokine supportive therapy. Patients with impaired renal function are at high risk of methotrexate toxicity, and low-dose methotrexate should be prescribed with great caution.

  14. Atopic dermatitis: clinical relevance of food hypersensitivity reactions.

    PubMed

    Burks, A W; Mallory, S B; Williams, L W; Shirrell, M A

    1988-09-01

    Forty-six patients with atopic dermatitis ranging from mild to severe were evaluated for food hypersensitivity with double-blind placebo-controlled food challenges. Twenty-eight (61%) patients had a positive prick skin reaction to one of the foods tested. Sixty-five food challenges were performed; 27 (42%) were interpreted as positive in 15 (33%) patients. Egg, milk, and peanut accounted for 78% of the positive reactions. As in previous studies, patients developed skin (96%), respiratory (52%), or gastrointestinal (30%) symptoms during the challenge. These studies indicate that children who have atopic dermatitis unresponsive to routine therapy or who continue to need daily treatment after several months would benefit from evaluation for food hypersensitivity.

  15. Environmental Hypersensitivity Disorder, Total Allergy and 20th Century Disease

    PubMed Central

    Stewart, D.E.

    1987-01-01

    Environmental hypersensitivity disorder is reputed to cause multiple allergic responses in susceptible people after exposure to common substances in the environment. The seriously afflicted, who believe themselves to be unable to live in the modern world, often become severely disabled. After a careful search of the literature, I am unable to find any scientific evidence for the validity of the theories, testing methods, or treatments given to these patients by clinical ecologists. This paper critically examines the concepts of environmental hypersensitivity and reviews scientific studies on this subject. It concludes that these patients are a heterogeneous group, and that many of them suffer from treatable psychiatric disorders. Guidelines are given for their management. PMID:21263833

  16. Laser-assisted treatment of dentinal hypersensitivity: a literature review

    PubMed Central

    Biagi, Roberto; Cossellu, Gianguido; Sarcina, Michele; Pizzamiglio, Ilaria Tina; Farronato, Giampietro

    2015-01-01

    Summary The purpose of this literature review was to evaluate the effectiveness of the laser-assisted treatment of dentinal hypersensitivity. A review with inclusion and exclusion criteria was performed from January 2009 to December 2014 with electronic data-bases: MedLine via PubMed, Science Direct and Cochrane Library. Research of paper magazines by hand was not considered. Forty-three articles were selected between literature reviews, in vitro studies, clinical trials, pilot and preliminary studies. The items were divided into laser-used groups for an accurate description, and then the reading of results into various typologies. Laser-assisted treatment reduces dentinal hypersensitivity-related pain, but also a psychosomatic component must be considered, so further studies and more suitable follow-ups are necessary. PMID:26941892

  17. Laser-assisted treatment of dentinal hypersensitivity: a literature review.

    PubMed

    Biagi, Roberto; Cossellu, Gianguido; Sarcina, Michele; Pizzamiglio, Ilaria Tina; Farronato, Giampietro

    2015-01-01

    The purpose of this literature review was to evaluate the effectiveness of the laser-assisted treatment of dentinal hypersensitivity. A review with inclusion and exclusion criteria was performed from January 2009 to December 2014 with electronic data-bases: MedLine via PubMed, Science Direct and Cochrane Library. Research of paper magazines by hand was not considered. Forty-three articles were selected between literature reviews, in vitro studies, clinical trials, pilot and preliminary studies. The items were divided into laser-used groups for an accurate description, and then the reading of results into various typologies. Laser-assisted treatment reduces dentinal hypersensitivity-related pain, but also a psychosomatic component must be considered, so further studies and more suitable follow-ups are necessary. PMID:26941892

  18. Studies of the quenching phenomenon in delayed contact hypersensitivity reactions.

    PubMed

    Basketter, D A; Allenby, C F

    1991-09-01

    Studies in guinea pig and man have shown that eugenol can quench non-specifically contact urticarial responses, whereas limonene seems largely ineffective. In a comprehensive series of studies, there was little evidence of quenching of delayed contact hypersensitivity reactions to cinnamic aldehyde or citral, including in 'pre-quenched' material supplied by a perfume/flavour company, and in a similar mixture prepared in this laboratory, in the guinea pig model. In addition, there was no evidence of the quenching by eugenol of allergic reactions to cinnamic aldehyde in a panel of human subjects with a proven history of cinnamic-aldehyde-induced allergic contact dermatitis. Overall, the results lend little credibility to earlier literature reports of quenching phenomena in delayed contact hypersensitivity responses.

  19. Cow's milk protein allergy and other food hypersensitivities in infants.

    PubMed

    Venter, Carina

    2009-01-01

    Food hypersensitivity (FHS) is the umbrella term used to describe both food allergy, which involves the immune system, and food intolerances, which do not. It is therefore important that the diagnosis is made by a specialist health care professional such as a paediatrician or allergist. Some experienced dietitians and health visitors may be able to assist in making a diagnosis. The diagnostic work-up includes a medical history and blood tests/skin tests (where applicable). A food and symptom diary followed by a special test diet to identify the foods causing the infant's symptoms may also be needed. Once a diagnosis is made, dietary advice should be given to eliminate or reduce the intake of the offending foods. For cow's milk hypersensitivity in infants, this will include choosing the most appropriate specialised infant formula. PMID:19953752

  20. Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions

    PubMed Central

    Böhm, Ruwen; Cascorbi, Ingolf

    2016-01-01

    Adverse drug reactions adverse drug reaction (ADR) occur in approximately 17% of patients. Avoiding ADR is thus mandatory from both an ethical and an economic point of view. Whereas, pharmacogenetics changes of the pharmacokinetics may contribute to the explanation of some type A reactions, strong relationships of genetic markers has also been shown for drug hypersensitivity belonging to type B reactions. We present the classifications of ADR, discuss genetic influences and focus on delayed-onset hypersensitivity reactions, i.e., drug-induced liver injury, drug-induced agranulocytosis, and severe cutaneous ADR. A guidance how to read and interpret the contingency table is provided as well as an algorithm whether and how a test for a pharmacogenetic biomarker should be conducted.

  1. Severe type IV hypersensitivity to 'black henna' tattoo.

    PubMed

    Vasilakis, Vasileios; Knight, Bernice; Lidder, Satnam; Frankton, Sarah

    2010-01-01

    A 16-year-old Bangladeshi girl presented with a 9-day history of an extensive pruritic, erythematous, papulovesicular skin eruption to both forearms. Appearance was 5 days following application of a home-made henna preparation. Examination revealed ulceration and scabbing along the whole henna pattern and early keloid formation. A diagnosis of type IV delayed hypersensitivity reaction superimposed by infection was initially made. As in this case, home-made henna preparations commonly combine commercial henna with black hair dye, paraphenylenediamine (PPD). PPD, widely known as 'black henna', darkens the pigment and precipitates the drying process. PPD is a potent contact allergen associated with a high incidence of hypersensitivity reactions. Despite treatment the patient was left with extensive keloid scarring in the pattern of the henna tattoo. PMID:22778139

  2. 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.

  3. 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

  4. 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.

  5. Value of bronchoalveolar lavage in the management of severe acute pneumonia and interstitial pneumonitis in the immunocompromised child.

    PubMed Central

    de Blic, J; McKelvie, P; Le Bourgeois, M; Blanche, S; Benoist, M R; Scheinmann, P

    1987-01-01

    The diagnostic value of 73 bronchoalveolar lavages was assessed in 67 immunocompromised children (aged 3 months to 16 years) with pulmonary infiltrates. Thirty one children had primary and 19 secondary immune deficiency, 14 acquired immunodeficiency syndrome (AIDS), and three AIDS related complex. Bronchoalveolar lavage was performed during fibreoptic bronchoscopy, under local anaesthesia in all but two. One or more infective agents was found in eight of 11 patients with severe acute pneumonia and in 26 of 62 patients with interstitial pneumonitis. In interstitial pneumonitis, the most frequently encountered agents were Pneumocystis carinii (12), cytomegalovirus (8), and Aspergillus fumigatus (3). The yield was related to the severity of interstitial pneumonitis. The mean cellular count and cytological profile in lavage returns from patients with varying infective agents or underlying pathological conditions showed no significant difference, except in those children with AIDS and AIDS related complex who had appreciable lymphocytosis (mean percentage of lymphocytes 28 (SD 17]. In children with AIDS and chronic interstitial pneumonitis lymphocytosis without pneumocystis infection was observed in eight of nine bronchoalveolar lavage returns and was suggestive of pulmonary lymphoid hyperplasia. Finally, bronchoalveolar lavage produced a specific diagnosis from the microbiological or cytological findings in 44 instances (60%). Transient exacerbation of tachypnoea was observed in the most severely ill children but there was no case of respiratory decompensation attributable to the bronchoscopy. Bronchoalveolar lavage is a safe and rapid examination for the investigation of pulmonary infiltrates in immunocompromised children. It should be performed as a first line investigation and should reduce the use of open lung biopsy techniques. PMID:2827334

  6. Minocycline hypersensitivity syndrome with hypotension mimicking septic shock.

    PubMed

    Colvin, J H; Sheth, A P

    2001-01-01

    Minocycline is a semisynthetic tetracycline derivative that is often used in the treatment of acne vulgaris. A serious but rare adverse effect caused by minocycline therapy is a hypersensitivity syndrome (HS), consisting of fever, skin eruption, and internal organ involvement that begins within 8 weeks of therapy initiation. We report a case of minocycline HS with unique features, namely, associated hypotension, and a rebound of the cutaneous eruption upon discontinuation of systemic steroids.

  7. Pragmatism and the evaluation of metal hypersensitivity reactions.

    PubMed

    Schalock, Peter C

    2013-01-01

    Evaluating patients with potential metal hypersensitivity reactions is challenging. Clear evidence-based guidelines based on randomized studies are lacking. A pragmatic approach to evaluation of these patients is useful due to this lack of evidence. Patch testing remains the gold standard for evaluating type IV reactions on the skin and is also likely the best test for metal reactions to implanted devices until more hard data is available.

  8. Angioneurotic edema: a rare case of hypersensitivity to metoclopramide

    PubMed Central

    Zakrzewski, Aleksander; Matuszewski, Tomasz; Kruszewski, Jerzy

    2013-01-01

    The case of a 30-year-old woman who had already experienced two incidents of angioneurotic edema and urticaria caused by drugs during the acute gastroenteritis. The allergological workup revealed hypersensitivity to metoclopramide. This case documents that metoclopramide, a drug commonly used to inhibit the vomiting, may cause not only bronchospastic reaction in an asthmatic patient but also angioneurotic edema of the tongue and larynx as well as urticaria. No similar cases in the literature were found. PMID:24278059

  9. Intestinal Membrane Permeability and Hypersensitivity In the Irritable Bowel Syndrome

    PubMed Central

    Zhou, QiQi; Zhang, Buyi; Verne, G. Nicholas

    2009-01-01

    Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the underlying pathophysiology is poorly understood; however, increased intestinal permeability in diarrhea-predominant IBS patients has been reported. Here we demonstrate diarrhea-predominant IBS patients (D-IBS) that display increased intestinal permeability. We have also found that increased intestinal membrane permeability is associated with visceral and thermal hypersensitivity in this subset of D-IBS patients. We evaluated 54 D-IBS patients and 22 controls for intestinal membrane permeability using the lactulose / mannitol method. All subjects ingested 5 g laclulose and 2 g mannitol in 100 ml of water after which their urine was collected. We also evaluated the mean mechanical visual analogue (MVAS) pain rating to nociceptive thermal and visceral stimulation in all subjects. All study participants also completed the FBDSI scale. Approximately 39% of diarrhea-predominant IBS patients have increased intestinal membrane permeability as measured by the lactulose / mannitol ratio. These IBS patients also demonstrated higher M-VAS pain intensity reading scale. Interestingly, the IBS patients with hypersensitivity and increased intestinal permeability had a higher FBDSI score (100.8±5.4) compared to IBS patients with normal membrane permeability and sensitivity (51.6±12.7) and controls (6.1 ± 5.6) (p<0.001). A subset of D-IBS patients have increased intestinal membrane permeability that is associated with an increased FBDSI score and increased hypersensitivity to visceral and thermal nociceptive pain stimuli. Thus, increased intestinal membrane permeability in D-IBS patients may lead to more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli. PMID:19595511

  10. 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.

  11. 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

  12. 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

  13. 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

  14. Risk factors for pneumonic and ulceroglandular tularaemia in Finland: a population-based case-control study.

    PubMed

    Rossow, H; Ollgren, J; Klemets, P; Pietarinen, I; Saikku, J; Pekkanen, E; Nikkari, S; Syrjälä, H; Kuusi, M; Nuorti, J P

    2014-10-01

    Few population-based data are available on factors associated with pneumonic and ulceroglandular type B tularaemia. We conducted a case-control study during a large epidemic in 2000. Laboratory-confirmed case patients were identified through active surveillance and matched control subjects (age, sex, residency) from the national population information system. Data were collected using a self-administered questionnaire. A conditional logistic regression model addressing missing data with Bayesian full-likelihood modelling included 227 case patients and 415 control subjects; reported mosquito bites [adjusted odds ratio (aOR) 9·2, 95% confidence interval (CI) 4·4-22, population-attributable risk (PAR) 82%] and farming activities (aOR 4·3, 95% CI 2·5-7·2, PAR 32%) were independently associated with ulceroglandular tularaemia, whereas exposure to hay dust (aOR 6·6, 95% CI 1·9-25·4, PAR 48%) was associated with pneumonic tularaemia. Although the bulk of tularaemia type B disease burden is attributable to mosquito bites, risk factors for ulceroglandular and pneumonic forms of tularaemia are different, enabling targeting of prevention efforts accordingly.

  15. Cracking the egg: An insight into egg hypersensitivity.

    PubMed

    Dhanapala, Pathum; De Silva, Chamika; Doran, Tim; Suphioglu, Cenk

    2015-08-01

    Hypersensitivity to the chicken egg is a widespread disorder mainly affecting 1-2% of children worldwide. It is the second most common food allergy in children, next to cow's milk allergy. Egg allergy is mainly caused by hypersensitivity to four allergens found in the egg white; ovomucoid, ovalbumin, ovotransferrin and lysozyme. However, some research suggests the involvement of allergens exclusively found in the egg yolk such as chicken serum albumin and YGP42, which may play a crucial role in the overall reaction. In egg allergic individuals, these allergens cause conditions such as itching, atopic dermatitis, bronchial asthma, vomiting, rhinitis, conjunctivitis, laryngeal oedema and chronic urticaria, and anaphylaxis. Currently there is no permanent cure for egg allergy. Upon positive diagnosis for egg allergy, strict dietary avoidance of eggs and products containing traces of eggs is the most effective way of avoiding future hypersensitivity reactions. However, it is difficult to fully avoid eggs since they are found in a range of processed food products. An understanding of the mechanisms of allergic reactions, egg allergens and their prevalence, egg allergy diagnosis and current treatment strategies are important for future studies. This review addresses these topics and discusses both egg white and egg yolk allergy as a whole.

  16. Expert opinion on the cough hypersensitivity syndrome in respiratory medicine.

    PubMed

    Morice, Alyn H; Millqvist, Eva; Belvisi, Maria G; Bieksiene, Kristina; Birring, Surinder S; Chung, Kian Fan; Dal Negro, Roberto W; Dicpinigaitis, Peter; Kantar, Ahmad; McGarvey, Lorcan P; Pacheco, Adalberto; Sakalauskas, Raimundas; Smith, Jaclyn A

    2014-11-01

    In 2011, a European Respiratory Society Task Force embarked on a process to determine the position and clinical relevance of the cough hypersensitivity syndrome, a disorder characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure, in the management of patients with chronic cough. A 21-component questionnaire was developed by an iterative process supported by a literature review. 44 key opinion leaders in respiratory medicine were selected and interviewed as to their opinions. There was a high degree of unanimity in the responses obtained, with all opinion leaders supporting the concept of cough hypersensitivity as a clinically useful paradigm. The classic stratification of cough into asthmatic, rhinitic and reflux-related phenotypes was supported. Significant disparity of opinion was seen in the response to two questions concerning the therapy of chronic cough. First, the role of acid suppression in reflux cough was questioned. Secondly, the opinion leaders were split as to whether a trial of oral steroids was indicated to establish a diagnosis of eosinophilic cough. The cough hypersensitivity syndrome was clearly endorsed by the opinion leaders as a valid and useful concept. They considered that support of patients with chronic cough was inadequate and the Task Force recommends that further work is urgently required in this neglected area.

  17. Food hypersensitivity among adult patients: epidemiological and clinical aspects.

    PubMed

    Castillo, R; Delgado, J; Quiralte, J; Blanco, C; Carrillo, T

    1996-01-01

    Food hypersensitivity (FH) is lesser frequent among adult patients than in childhood. Foods implicated in hypersensitivity reactions vary with sociocultural and diet habits from a geographic place to other. We studied 142 adult patients sensitized to foods, among 7698 patients visited at our Outpatient Clinic. Hundred and twenty patients referred clinical symptoms after consumption of one or more foods consistently. From the latest, 107 patients (89.2%) were atopics (92 of them sensitizes to dust mites) and 54 (45%) referred atopic familiar background. Most frequent recorded symptoms were: urticaria/angioedema 84 cases (70%), oral syndrome 65 (54%), asthma 48 (37%) and anaphylaxis 33 patients (27.5%). Shellfish sensitization occurred in 50 patients, fresh fruits in 33 and nuts in 29 cases. Shrimp (48 patients), squid (33), kiwi (14), papaya (14), avocado (13) and banana (12 cases) were the most frequent causes of FH. Significant statistical association between foods and inhalants was observed for fresh fruits and latex (p < 0.001), fresh fruits and pollens (p < 0.01), and shellfish and Blatta germanica (p < 0.001). Prevalence of FH among patients at our Area is around 1.6%. Tropical fruits, as other kind of fruits, seem to share common IgE-epitopes to pollens. High prevalence of shellfish and cockroach hypersensitivity could be more easily developed by previous domestic mites sensitization.

  18. Hypersensitivity to antineoplastic agents: mechanisms and treatment with rapid desensitization.

    PubMed

    Castells, Mariana; Sancho-Serra, Maria del Carmen; Simarro, Maria

    2012-09-01

    Hypersensitivity reactions (HSRs) to chemotherapy drugs, such as taxanes and platins, and to monoclonal antibodies limit their therapeutic use due to the severity of some reactions and the fear of inducing a potentially lethal reaction in highly sensitized patients. Patients who experience hypersensitivity reactions face the prospect of abandoning first-line treatment and switching to a second-line, less effective therapy. Some of these reactions are mast cell-mediated hypersensitivity reactions, a subset of which occur through an immunoglobulin (IgE)-dependent mechanism, and are thus true allergies. Others involve mast cells without a demonstrable IgE mechanism. Whether basophils can participate in these reactions has not been demonstrated. Rapid drug desensitization (RDD) is a procedure that induces temporary tolerance to a drug, allowing a medication allergic patient to receive the optimal agent for his or her disease. Through RDD, patients with IgE and non-IgE HSRs can safely be administered important medications while minimizing or completely inhibiting adverse reactions. Due to the clinical expansion and success of RDD, the molecular mechanisms inducing the temporary tolerization have been investigated and are partially understood, allowing for safer and more effective protocols. This article reviews the current literature on molecular mechanisms of RDD with an emphasis in our recent contributions to this field as well as the indications, methods and outcomes of RDD for taxanes, platins, and monoclonal antibodies. PMID:22576054

  19. The evaluation of hypersensitivity tests in cattle after foot-and-mouth disease vaccination.

    PubMed Central

    Black, L.; Pay, T. W.

    1975-01-01

    The response to passive cutaneous anaphylaxis, dermal hypersensitivity and intravenous provocation tests has been compared in 30, 40, 31 and 24 cattle injected with foot-and-mouth disease vaccine 0, 1, 2 and 3 times respectively, using vaccine components and other substances as test materials. Reaginic antibodies demonstrated by passive cutaneous anaphylaxis in goats, were directed against BHK 21 cell extracts (20), hydroxypropylmethylcellulose (3) and an unidentified vaccine component (3), and distributed in 0, 5, 19 and 75 per cent of the cattle vaccinated 0, 1, 2 and 3 times. None of the animals showed clinical signs of allergy after vaccination. When BHK 21 cell extract was injected intradermally a significant correlation was noted between the development of large weals and the presence of reagins although the size of the weals was not correlated with the reagin titres. In the case of hydroxypropylmethylcellulose a similar trend was evident. The majority of cattle with large dermal weals possessed reagins but the number of reactions was too small for statistical evaluation. Dermal reactions to sodium penicillin, sodium carboxymethylcellulose, saponin and whole vaccine occurred in both unvaccinated and vaccinated cattle but BHK 21 cell lysate and normal bovine serum provoked weals which increased in frequency according to the number of vaccinations experienced. Intravenous hydroxypropylmethylcellulose elicited a response in all the animals previously injected with certain batches of vaccine but cell extract intravenously produced a clinical response in half the tested animals which was uncorrelated with the results of the passive cutaneous anaphylaxis or dermal hypersensitivity tests. Images Plate 1 PMID:1054725

  20. 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.

  1. Predictive Factors for Radiation Pneumonitis in Hodgkin Lymphoma Patients Receiving Combined-Modality Therapy

    SciTech Connect

    Fox, Amy M.; Dosoretz, Arie P.; Mauch, Peter M.; Chen, Yu-Hui; Fisher, David C.; LaCasce, Ann S.; Freedman, Arnold S.; Silver, Barbara; Ng, Andrea K.

    2012-05-01

    Purpose: This study sought to quantify the risk of radiation pneumonitis (RP) in Hodgkin lymphoma (HL) patients receiving mediastinal radiation therapy (RT) and to identify predictive factors for RP. Methods and Materials: We identified 75 patients with newly diagnosed HL treated with mediastinal RT and 17 patients with relapsed/refractory HL treated with mediastinal RT before or after transplant. Lung dose-volumetric parameters including mean lung dose and percentage of lungs receiving 20 Gy were calculated. Factors associated with RP were explored by use of the Fisher exact test. Results: RP developed in 7 patients (10%) who received mediastinal RT as part of initial therapy (Radiation Therapy Oncology Group Grade 1 in 6 cases). A mean lung dose of 13.5 Gy or greater (p = 0.04) and percentage of lungs receiving 20 Gy of 33.5% or greater (p = 0.009) significantly predicted for RP. RP developed in 6 patients (35%) with relapsed/refractory HL treated with peri-transplant mediastinal RT (Grade 3 in 4 cases). Pre-transplant mediastinal RT, compared with post-transplant mediastinal RT, significantly predicted for Grade 3 RP (57% vs. 0%, p = 0.015). Conclusions: We identified threshold lung metrics predicting for RP in HL patients receiving mediastinal RT as part of initial therapy, with the majority of cases being of mild severity. The risk of RP is significantly higher with peri-transplant mediastinal RT, especially among those who receive pre-transplant RT.

  2. The isolation of multiple strains of Mycoplasma ovipneumoniae from individual pneumonic sheep lungs.

    PubMed

    Ionas, G; Clarke, J K; Marshall, R B

    1991-11-01

    The heterogeneity of Mycoplasma ovipneumoniae isolates from the lungs of sheep with chronic non-progressive pneumonia (CNP) from the same flock raised the possibility that multiple isolates derived from one lung were not all identical. To test this hypothesis, thirty isolates were obtained from each of six pneumonic sheep lungs at slaughter. Four lungs had relatively severe lesions and from each of these, three or four strains of M. ovipneumonia, distinguishable by REA and in most cases by SDS-PAGE, were detected. From the lungs of each of two sheep with mild lesions, two strains of M. ovipneumoniae were detected. Four isolates from one lung were further examined by restriction endonuclease analysis (REA) using many restriction endonucleases. Those which differed with EcoRI also differed when other restriction endonucleases were used. However, partial digests occurred mainly with those restriction endonucleases which recognise cytosine-rich sequences. The presence of multiple strains of one species of microorganism in individual lesions is an unusual concept which may not be limited to one disease or to one host.

  3. 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

  4. Efficacy evaluations of the use of oral tilmicosin in pneumonic calves.

    PubMed

    Fodor, L; Reeve-Johnson, L; Hodge, A; Varga, J

    2000-03-01

    The therapeutic effect of oral tilmicosin was compared with enrofloxacin, and the efficacy of three doses of the drug was examined in two fully randomized blinded field trials. Pneumonic milk-fed calves between 3 days and 2.5 months of age were allocated into two groups in trial 1 (50 animals) and into three groups in trial 2 (69 calves). In the first trial, the animals were treated with 25 mg/kg/day tilmicosin or 2.5 mg/kg/day enrofloxacin in milk for 5 days. In the second trial, the calves received either 25 mg/kg/day tilmicosin for 5 days or 3 days, or else 12.5 mg/kg tilmicosin for 5 days. All calves were clinically examined for 10 days. In the first trial, oral tilmicosin at a dose of 25 mg/kg/day for 5 days proved to be effective for the treatment of endemic pasteurellosis of milk-fed calves. The efficacy was the same as that of enrofloxacin. All three doses in the second trial were effective and were statistically equivalent to the original dose tested.

  5. Respiratory morbidity from lymphocytic interstitial pneumonitis (LIP) in vertically acquired HIV infection.

    PubMed

    Sharland, M; Gibb, D M; Holland, F

    1997-04-01

    The aim of the study was to define the respiratory morbidity caused by lymphocytic interstitial pneumonitis (LIP) in children with vertically acquired HIV infection. A retrospective case note review was performed on 95 children attending three London hospitals. Clinical and radiological evidence of LIP, acute lower respiratory tract infections, and chronic lung disease was obtained using a structured protocol. A diagnosis of LIP had been made in 33%, and an acute admission due to acute lower respiratory tract infection had occurred in 42% of all children (despite 99% taking regular cotrimoxazole prophylaxis). Admission rates because of acute lower respiratory tract infection were significantly higher in the LIP group (0.38 admissions/child year) than in the non-LIP group (0.17 admissions/child year) (p = 0.0002). Encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae) were most frequently isolated. Improved methods of prevention of acute lower respiratory tract infection may help to reduce the severe respiratory morbidity seen in children with LIP and HIV infection. PMID:9166026

  6. Cytomegalovirus pneumonitis and bone marrow transplantation: identification of a specific high risk group.

    PubMed Central

    Foot, A B; Caul, E O; Roome, A P; Darville, J M; Oakhill, A

    1993-01-01

    AIMS--To study the association between cytomegalovirus (CMV) excretion and interstitial pneumonitis in allogeneic bone marrow transplant (BMT) recipients, with reference to donor and recipient CMV antibody response. METHODS--The incidence of CMV excretion was prospectively studied in 62 allogeneic bone marrow transplantations performed on adults and children. All recipients received CMV seronegative blood products. Prophylaxis with high dose acyclovir and CMV immune globulin was given to high risk patients (donor or recipient, or both, CMV seropositive). RESULTS--CMV excretion was detected in eight of 26 (31%) high risk patients but in only one of 36 low risk patients (donor and recipient both CMV seronegative). Five of the eight (63%) excretors in the high risk category developed CMV, of whom four (80%) belonged to the seropositive recipient/seronegative donor group, and included the three CMV seropositive recipients whose CMV complement fixation antibody titres were 64 or greater before transplantation. CONCLUSIONS--These findings suggest that there is a subgroup of patients at especially high risk of developing CMV. PMID:8391547

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

    PubMed Central

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

    2016-01-01

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

  8. Hypersensitivity Reaction to High-Dose Methotrexate and Successful Rechallenge in a Pediatric Patient with Osteosarcoma

    PubMed Central

    Scott, Jeffrey R.; Ward, Deborah A.; Crews, Kristine R.; Panetta, John C.; Navid, Fariba

    2014-01-01

    Hypersensitivity reactions to methotrexate are rare, but have been reported. Methotrexate has shown activity against many malignancies, and omission of methotrexate therapy may increase the risk of cancer-related death in some patients. Therefore, rechallenging patients with methotrexate following hypersensitivity may be beneficial. We report a case of a child with metastatic osteosarcoma who experienced a hypersensitivity reaction to high-dose methotrexate and was successfully rechallenged with methotrexate using a 6-hour infusion. Using this regimen, adequate peak methotrexate plasma concentrations were achieved and no further hypersensitivity reactions were noted. PMID:23955991

  9. HLA Associations and Clinical Implications in T-Cell Mediated Drug Hypersensitivity Reactions: An Updated Review

    PubMed Central

    Cheng, Chi-Yuan; Chen, Chi-Hua; Chen, Wei-Li; Deng, Shin-Tarng; Chung, Wen-Hung

    2014-01-01

    T-cell mediated drug hypersensitivity reactions may range from mild rash to severe fatal reactions. Among them, drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS), Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN), are some of the most life-threatening severe cutaneous adverse reactions (SCARs). Recent advances in pharmacogenetic studies show strong genetic associations between human leukocyte antigen (HLA) alleles and susceptibility to drug hypersensitivity. This review summarizes the literature on recent progresses in pharmacogenetic studies and clinical application of pharmacogenetic screening based on associations between SCARs and specific HLA alleles to avoid serious conditions associated with drug hypersensitivity. PMID:24901010

  10. Relationship between Sympathetic Skin Responses and Auditory Hypersensitivity to Different Auditory Stimuli

    PubMed Central

    Kato, Fumi; Iwanaga, Ryoichiro; Chono, Mami; Fujihara, Saori; Tokunaga, Akiko; Murata, Jun; Tanaka, Koji; Nakane, Hideyuki; Tanaka, Goro

    2014-01-01

    [Purpose] Auditory hypersensitivity has been widely reported in patients with autism spectrum disorders. However, the neurological background of auditory hypersensitivity is currently not clear. The present study examined the relationship between sympathetic nervous system responses and auditory hypersensitivity induced by different types of auditory stimuli. [Methods] We exposed 20 healthy young adults to six different types of auditory stimuli. The amounts of palmar sweating resulting from the auditory stimuli were compared between groups with (hypersensitive) and without (non-hypersensitive) auditory hypersensitivity. [Results] Although no group × type of stimulus × first stimulus interaction was observed for the extent of reaction, significant type of stimulus × first stimulus interaction was noted for the extent of reaction. For an 80 dB-6,000 Hz stimulus, the trends for palmar sweating differed between the groups. For the first stimulus, the variance became larger in the hypersensitive group than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt excessive reactions to auditory stimuli tended to have excessive sympathetic responses to repeated loud noises compared with subjects who did not feel excessive reactions. People with auditory hypersensitivity may be classified into several subtypes depending on their reaction patterns to auditory stimuli. PMID:25140103

  11. Relationship between Sympathetic Skin Responses and Auditory Hypersensitivity to Different Auditory Stimuli.

    PubMed

    Kato, Fumi; Iwanaga, Ryoichiro; Chono, Mami; Fujihara, Saori; Tokunaga, Akiko; Murata, Jun; Tanaka, Koji; Nakane, Hideyuki; Tanaka, Goro

    2014-07-01

    [Purpose] Auditory hypersensitivity has been widely reported in patients with autism spectrum disorders. However, the neurological background of auditory hypersensitivity is currently not clear. The present study examined the relationship between sympathetic nervous system responses and auditory hypersensitivity induced by different types of auditory stimuli. [Methods] We exposed 20 healthy young adults to six different types of auditory stimuli. The amounts of palmar sweating resulting from the auditory stimuli were compared between groups with (hypersensitive) and without (non-hypersensitive) auditory hypersensitivity. [Results] Although no group × type of stimulus × first stimulus interaction was observed for the extent of reaction, significant type of stimulus × first stimulus interaction was noted for the extent of reaction. For an 80 dB-6,000 Hz stimulus, the trends for palmar sweating differed between the groups. For the first stimulus, the variance became larger in the hypersensitive group than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt excessive reactions to auditory stimuli tended to have excessive sympathetic responses to repeated loud noises compared with subjects who did not feel excessive reactions. People with auditory hypersensitivity may be classified into several subtypes depending on their reaction patterns to auditory stimuli.

  12. Delayed hypersensitivity to a corticosteroid suspension containing methylprednisolone. Two cases of conjunctival inflammation after retrobulbar injection.

    PubMed

    Mathias, C G; Robertson, D B

    1985-02-01

    Two patients with chronic iridocyclitis had a delayed hypersensitivity reaction, characterized by severe conjunctival inflammation, after retrobulbar injections with a commercial suspension of methylprednisolone acetate. Although patch test reactions to methylprednisolone at enhanced concentrations were negative, delayed hypersensitivity could be easily demonstrated by intradermal testing with this corticosteroid. Both patients also had concomitant delayed hypersensitivity to a proprietary preservative (myristyl gamma-picolinium chloride) in the commercial corticosteroid suspension, which was confirmed by intradermal testing. These observations (negative patch test reactions, positive intradermal test reactions) suggest that the route of administration may be an important determinant of antigenic hapten-protein complex formation and subsequent delayed hypersensitivity responses involving cutaneous or mucocutaneous tissue.

  13. Studies on the mechanism of systemic suppression of contact hypersensitivity by UVB radiation. II. Differences in the suppression of delayed and contact hypersensitivity in mice.

    PubMed

    Kripke, M L; Morison, W L

    1986-05-01

    Exposing mice to UV radiation in the UVB range (280-320 nm) causes a selective immune suppression that contributes to the development of UVB-induced skin cancers. Among the immune responses suppressed by UVB irradiation are contact and delayed hypersensitivity reactions to haptens administered at unexposed sites. In these studies we provide evidence that delayed and contact hypersensitivity to the same hapten are not equivalent reactions and that they are suppressed in UVB-irradiated mice by 2 different mechanisms. This conclusion is based on the findings that: suppression of contact hypersensitivity could not be overcome by immunizing UVB-irradiated mice with hapten-coupled antigen-presenting cells derived from normal donors; and treatment of UVB-irradiated mice with methylprednisolone before immunization prevented the suppression of delayed hypersensitivity but had no effect on the suppression of contact hypersensitivity. The decreased ability to induce contact hypersensitivity in UVB-irradiated mice could be transferred to x-irradiated mice by reconstituting them with spleen cells from UVB-irradiated donors. The induction of hapten-specific suppressor cells, however, required both UVB irradiation and priming with hapten. Based on these results, we postulate that UVB irradiation induces a population of suppressor-inducer cells with specificity for a modified skin antigen and that this antigen serves as a carrier molecule for haptens that induce contact hypersensitivity and for tumor-specific transplantation antigens on UVB-induced tumors. PMID:3745963

  14. Biomaterial hypersensitivity: is it real? Supportive evidence and approach considerations for metal allergic patients following total knee arthroplasty.

    PubMed

    Mitchelson, Andrew J; Wilson, Craig J; Mihalko, William M; Grupp, Thomas M; Manning, Blaine T; Dennis, Douglas A; Goodman, Stuart B; Tzeng, Tony H; Vasdev, Sonia; Saleh, Khaled J

    2015-01-01

    The prospect of biomaterial hypersensitivity developing in response to joint implant materials was first presented more than 30 years ago. Many studies have established probable causation between first-generation metal-on-metal hip implants and hypersensitivity reactions. In a limited patient population, implant failure may ultimately be related to metal hypersensitivity. The examination of hypersensitivity reactions in current-generation metal-on-metal knee implants is comparatively limited. The purpose of this study is to summarize all available literature regarding biomaterial hypersensitivity after total knee arthroplasty, elucidate overall trends about this topic in the current literature, and provide a foundation for clinical approach considerations when biomaterial hypersensitivity is suspected.

  15. Hypersensitivity reaction to components of parenteral nutrition in pediatrics.

    PubMed

    Hernández, Carlos Ruiz; Ponce, Esperanza Castejón; Busquets, Ferran Bossacoma; Hernández, Diana Sánchez; Oliva, Silvia Meavilla; Santacruz, Enrique Llerena; Pérez, Naymar; De Los Santos Pelegrini, Mariela; Flaque, Miquel Villaronga

    2016-01-01

    Very rare cases of hypersensitivity reactions to various constituents of parenteral nutrition (PN) have been reported in children. Adverse effects associated with PN administration have centered on metabolic, infectious, and mechanical complications. Here we describe three cases of hypersensitivity to components of PN. Case 1 is a 1-mo-old breastfed baby with a diagnosis of acute gastroenteritis associated with an infection with cytomegalovirus. On the second day of PN, 60 min after the initiation of the infusion, the patient had an allergic reaction with an overall diffused rash. On day 4 of PN, the multivitamin solution and the trace element mix were excluded, showing a good tolerance. Case 2 is a 4-y-old girl with a background of stage III neuroblastoma. On day 3 of PN, 15 min after the initiation of the infusion, the patient showed sudden facial edema. On day 5, suspecting the amino acid solution to be the etiology of her reaction, PN was infused with another amino acid preparation, and the patient showed good tolerance. Case 3 is a 10-y-old boy with a diagnosis of an acute peritonitis. Two h after the initiation of the infusion, the patient showed a general wheal rash. He referred a background of fish allergy. Considering that the lipid emulsion used had components from fish oil (SMOF Lipid), a new PN was infused on day 2. The new PN contained a lipid emulsion containing vegetable oil (ClinOleic). The patient showed good tolerance. In conclusion, we consider that, although the hypersensitivity to PN components is infrequent, there is an increase in reports of pediatric cases describing this allergic pathology.

  16. Effect of a fluoride solution on dentinal hypersensitivity.

    PubMed

    Thrash, W J; Jones, D L; Dodds, W J

    1992-12-01

    This two-phase experiment assessed the effects over time of a solution containing 1.09% sodium fluoride, .40% stannous fluoride, and .14% hydrogen fluoride (.717% fluoride solution, DentinBloc) on pain associated with dentinal hypersensitivity. During phase I, 30 subjects demonstrating dentinal hypersensitivity to a blast of cool air were divided into three double blind experimental groups. After baseline data were collected for all subjects, one group was instructed to apply the .717% fluoride solution twice a day. A second group was instructed to apply a gel containing .04% stannous fluoride (Gel-Kam) twice a day. A third group was instructed to apply distilled water. Each subject was assessed at 2, 4, 8, and 16 weeks utilizing the "method of limits" with a standardized, repeatable cold thermal stimulus. The results of a two factor repeated ANOVA indicated that those subjects who applied the .717% fluoride solution reported significantly less sensitivity at the 2-week period than the other groups (P < .05). In addition, those subjects whose solution contained the 0.4% stannous fluoride reported significantly less sensitivity at the 4- to 8-week periods (P < .05). Phase II of the study assessed the .717% fluoride solution on a more precise time course. These included: immediately, 15 minute, 1 day, 1 week and 2 weeks. A one factor repeated ANOVA revealed that this effect presented 15-minute post application (P < .05) and continued throughout the testing periods. It was concluded that the fully active 0.717% fluoride solution was an effective agent in the control of dentinal hypersensitivity after two 1-minute applications.

  17. Unusual formaldehyde-induced hypersensitivity in two schoolgirls

    SciTech Connect

    Gammage, R.B. ); Hanna, W.T.; Painter, P.B. )

    1990-01-01

    Two schoolgirls developed a syndrome resembling Henoch-Schonlein purpura while attending a recently opened school insulated with urea-formaldehyde foam (UFFI). Skin rashes and swellings were accompanied by bizarre, blue-green discoloration of the skin. Subsequent investigations by county, state and federal authorities, and low measured concentrations of formaldehyde, prompted initial conclusions that in-school formaldehyde exposures were not responsible for the girls' problems. Subsequent controlled exposures to UFFI and formaldehyde while in hospital elicited the whole cascade of symptoms. The chronology of the onset and amplification of systems make it probable that the formaldehyde exposures precipitating the girls' hypersensitivity, occurred in the school. 3 refs.

  18. Hypersensitive Transport in Photonic Crystals with Accidental Spatial Degeneracies.

    PubMed

    Makri, Eleana; Smith, Kyle; Chabanov, Andrey; Vitebskiy, Ilya; Kottos, Tsampikos

    2016-01-01

    A localized mode in a photonic layered structure can develop nodal points (nodal planes), where the oscillating electric field is negligible. Placing a thin metallic layer at such a nodal point results in the phenomenon of induced transmission. Here we demonstrate that if the nodal point is not a point of symmetry, then even a tiny alteration of the permittivity in the vicinity of the metallic layer drastically suppresses the localized mode along with the resonant transmission. This renders the layered structure highly reflective within a broad frequency range. Applications of this hypersensitive transport for optical and microwave limiting and switching are discussed. PMID:26903232

  19. Hypersensitive Transport in Photonic Crystals with Accidental Spatial Degeneracies

    PubMed Central

    Makri, Eleana; Smith, Kyle; Chabanov, Andrey; Vitebskiy, Ilya; Kottos, Tsampikos

    2016-01-01

    A localized mode in a photonic layered structure can develop nodal points (nodal planes), where the oscillating electric field is negligible. Placing a thin metallic layer at such a nodal point results in the phenomenon of induced transmission. Here we demonstrate that if the nodal point is not a point of symmetry, then even a tiny alteration of the permittivity in the vicinity of the metallic layer drastically suppresses the localized mode along with the resonant transmission. This renders the layered structure highly reflective within a broad frequency range. Applications of this hypersensitive transport for optical and microwave limiting and switching are discussed. PMID:26903232

  20. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2008.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2009-02-01

    This review highlights some of the research advances in anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects and in allergic skin disease that were reported in the Journal in 2008. Key epidemiologic observations include a rise in anaphylaxis in a population-based study and lower rates of peanut allergy in Israel, where infants consume peanut early compared with the United Kingdom, where dietary introduction is generally delayed. Advances in food allergy diagnosis include IgE epitope mapping that discloses the likelihood and severity of allergy; studies correlating likelihood of clinical reactivity on the basis of food-specific IgE to sesame, peanut, milk, and tree nuts; and an observation that a low baseline angiotensin-converting enzyme level may be associated with having pharyngeal edema during a reaction. Molecular, immunologic, and genetic studies are discerning pathways that are key in development of food allergy, identifying new modalities to interrupt mast cell degranulation, and elucidating risks associated with penicillin allergy. Regarding treatment, clinical studies show a majority of children with milk and egg allergy tolerate these proteins in modest amounts when they are extensively heated in baked goods, and studies show promise for oral immunotherapy to treat milk allergy and sublingual immunotherapy for honey bee venom hypersensitivity. The importance of skin barrier dysfunction has continued to be highlighted in the pathophysiology of atopic dermatitis (AD). Research has also continued to identify immunologic defects that contribute to the propensity of patients with AD to develop viral and bacterial infection. New therapeutic approaches to AD, urticaria, and angioedema have been reported including use of probiotics, biologics, vitamin D, and skin barrier creams.

  1. Alcohol and high fat induced chronic pancreatitis: TRPV4 antagonist reduces hypersensitivity.

    PubMed

    Zhang, L P; Kline, R H; Deevska, G; Ma, F; Nikolova-Karakashian, M; Westlund, K N

    2015-12-17

    The pathogenesis of pain in chronic pancreatitis is poorly understood, and its treatment can be a major clinical challenge. Surgical and other invasive methods have variable outcomes that can be unsatisfactory. Therefore, there is a great need for further discovery of the pathogenesis of pancreatitis pain and new therapeutic targets. Human and animal studies indicate a critical role for oxidative stress and activation of transient receptor potential (TRP) cation channel subfamily members TRPV1 and TRPA1 on pancreatic nociceptors in sensitization mechanisms that result in pain. However, the in vivo role of transient receptor potential cation channel subfamily V member 4 (TRPV4) in chronic pancreatitis needs further evaluation. The present study characterized a rat alcohol/high fat diet (AHF)-induced chronic pancreatitis model with hypersensitivity, fibrotic pathology, and fat vacuolization consistent with the clinical syndrome. The rats with AHF-induced pancreatitis develop referred visceral pain-like behaviors, i.e. decreased hindpaw mechanical thresholds and shortened abdominal and hindpaw withdrawal latency to heat. In this study, oxidative stress was characterized as well as the role of TRPV4 in chronic visceral hypersensitivity. Lipid peroxidase and oxidative stress were indicated by increased plasma thiobarbituric acid reactive substances (TBARS) and diminished pancreatic manganese superoxide dismutase (MnSOD). The secondary sensitization associated with AHF-induced pancreatitis was effectively alleviated by the TRPV4 antagonist, HC 067047. Similarity of the results to those with the peripherally restricted μ-opiate receptor agonist, loperamide, suggested TRPV4 channel activated peripheral sensitization. This study using a reliable model that provides pre-clinical correlates of human chronic pancreatitis provides further evidence that TRPV4 channel is a potential therapeutic target for treatment of pancreatitis pain.

  2. TH1/TH2 balance in concomitant immediate and delayed-type hypersensitivity diseases.

    PubMed

    de Mello, Luane Marques; Bechara, Monique Isabel Silveira; Solé, Dirceu; Rodrigues, Virmondes

    2009-06-01

    In spite of the observation of mutual inhibitory properties of TH1 and TH2 CD4+ cells, a group of patients developed simultaneously immediate and delayed-type hypersensitivity reactions that are theoretically antagonistic. Patients presenting concomitant hypersensitivity reactions were evaluated for cytokine production. PBMC from 45 patients and 13 non-atopic individuals were cultured with mite allergen and mitogen and the supernatants obtained were evaluated for cytokine production by ELISA. The analysis of the cytokines levels revealed increased production of pro-inflammatory cytokine TNF-alpha in the non-atopic individuals after specific and mitogen stimulus. The IL-4 was largely observed on serum samples and IL-5 levels were higher in the double sensitized group (group DerpNi) after PHA stimulus. The IL-13 levels were increased in sensitized groups (Derp and DerpNi groups) after PHA stimuli. Atopic patients (Derp and DerpNi groups) presented lowest levels IFN-gamma and the analysis of TGF-beta production after rDER P I stimulation have shown increased levels among sensitized patients to Dermatophagoides pteronyssinus mite. IL-10 levels did not differ after antigen stimulation but basal production was higher on Derp and DerpNi groups. Furthermore, negative correlations were observed between IFN-gamma levels and IL-4, IL-13 and IL-10. This study has shown patients able to react, concomitantly, to the two types of antigens - rDER P I and NiSO4, present distinct pattern of cytokine production. The increased levels of IL-13 in the sensitive individuals to mite antigen (rDER P I) and IFN-gamma in NiSO4 sensitized individuals confirm the role of the type TH2 response in the atopies and TH1 type in DCA. PMID:19433108

  3. NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity

    PubMed Central

    Norcini, Monica; Sideris, Alexandra; Adler, Samantha M.; Hernandez, Lourdes A. M.; Zhang, Jin; Blanck, Thomas J. J.; Recio-Pinto, Esperanza

    2016-01-01

    Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes. Using the electronic von Frey to stimulate the spared and non-spared regions of the hindpaws, we demonstrated that sural-SNI animals develop sustained neuropathic pain in both regions while the tibial-SNI animals recover. NR2B expression was measured at Day 23 and Day 86 post-injury. At Day 23 and 86 post-injury, sural-SNI animals display strong hypersensitivity, whereas tibial-SNI animals display 50 and 100% recovery from post-injury-induced hypersensitivity, respectively. In tibial-SNI at Day 86, but not at Day 23 the perinuclear region of the neuronal somata displayed an increase in NR2B protein. This retention of NR2B protein within the perinuclear region, which will render them non-functional, correlates with the recovery observed in tibial-SNI. In sural-SNI at Day 86, DRG displayed an increase in NR2B mRNA which correlates with the development of sustained hypersensitivity in this model. The increase in NR2B mRNA was not associated with an increase in NR2B protein within the neuronal somata. The latter may result from a decrease in kinesin Kif17, since Kif17 mediates NR2B transport to the soma’s plasma membrane. In both SNIs, microglia/macrophages showed a transient increase in NR2B protein detected at Day 23 but not at Day 86, which correlates with the initial post-injury induced hypersensitivity in both SNIs. In tibial-SNI at Day 86, but not at Day 23

  4. A neural network model to predict lung radiation-induced pneumonitis

    SciTech Connect

    Chen Shifeng; Zhou Sumin; Zhang Junan; Yin Fangfang; Marks, Lawrence B.; Das, Shiva K.

    2007-09-15

    A feed-forward neural network was investigated to predict the occurrence of lung radiation-induced Grade 2+ pneumonitis. The database consisted of 235 patients with lung cancer treated using radiotherapy, of whom 34 were diagnosed with Grade 2+ pneumonitis at follow-up. The network was constructed using an algorithm that alternately grew and pruned it, starting from the smallest possible network, until a satisfactory solution was found. The weights and biases of the network were computed using the error back-propagation approach. Momentum and variable leaning techniques were used to speed convergence. Using the growing/pruning approach, the network selected features from 66 dose and 27 non-dose variables. During network training, the 235 patients were randomly split into ten groups of approximately equal size. Eight groups were used to train the network, one group was used for early stopping training to prevent overfitting, and the remaining group was used as a test to measure the generalization capability of the network (cross-validation). Using this methodology, each of the ten groups was considered, in turn, as the test group (ten-fold cross-validation). For the optimized network constructed with input features selected from dose and non-dose variables, the area under the receiver operating characteristics (ROC) curve for cross-validated testing was 0.76 (sensitivity: 0.68, specificity: 0.69). For the optimized network constructed with input features selected only from dose variables, the area under the ROC curve for cross-validation was 0.67 (sensitivity: 0.53, specificity: 0.69). The difference between these two areas was statistically significant (p=0.020), indicating that the addition of non-dose features can significantly improve the generalization capability of the network. A network for prospective testing was constructed with input features selected from dose and non-dose variables (all data were used for training). The optimized network architecture

  5. 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

  6. The Influence of Radiotherapy on AIM2 Inflammasome in Radiation Pneumonitis.

    PubMed

    Zhang, Qianyu; Hu, Qinyong; Chu, Yuxin; Xu, Bin; Song, Qibin

    2016-10-01

    This study aims to investigate the influence of radiotherapy on absent in melanoma 2 (AIM2) inflammasome in radiation pneumonitis (RP). A rat model of RP was established. H&E staining was used to test radiation-induced lung tissue injury. Immunohistochemistry (IHC) was used to detect the expression of AIM2 and IL-1β in rat lung tissues. Milliplex assay was used to test cytokine levels in rat serum. Comet assay was adopted to examine DNA breaks in THP1 cells. RT-PCR was used to detect the messenger RNA (mRNA) expression of AIM2, caspase-1, and IL-1β in THP1 cells. As a result, the rat model indicated that irradiation induced obvious lung injury. A large amount of inflammatory cells infiltrated to the irradiated lung tissues. The structure of lung tissues collapsed. IHC revealed that AIM2 and IL-1β expressions were significantly higher in irradiated lung tissues than in the control. IL-1β level in rat serum significantly elevated on the 7th day post-irradiation, gradually decreased on the 15th day, and became minimal on the 30th day. Irradiation induced dsDNA break in a dose-dependent manner at 24 h after irradiation. Radiotherapy increased the mRNA expression level of AIM2 and IL-1β in a time-dependent manner. In conclusion, radiotherapy triggered some critical components of AIM2 inflammasome in RP. The activation of AIM2 inflammasome by radiotherapy may contribute to the pathogenesis of RP. PMID:27525422

  7. 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.

  8. 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

  9. 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.

  10. Risk of Pneumonitis after Stereotactic Body Radiation Therapy in Patients with Prior Anatomic Lung Resection

    PubMed Central

    Hayes, Jason T.; David, Elizabeth A.; Qi, LiHong; Chen, Allen M.; Daly, Megan E.

    2015-01-01

    Purpose/Objectives Stereotactic body radiation therapy (SBRT) has emerged as a standard treatment for early stage, medically inoperable lung cancer. Limited data evaluate radiation pneumonitis (RP) risk for SBRT following prior anatomic lung resection (ALR). We assess the incidence of RP and all pulmonary toxicity (PT) in patients treated with lung SBRT following ALR and compare to patients without prior ALR. Materials/Methods We reviewed the medical records of 84 consecutively treated patients with T1-T2b NSCLC treated with 88 courses of SBRT for 94 lung tumors from January 2007- December 2014, including 17 patients with prior ALR. Rates of RP and all PT were compared between patients with and without prior ALR. Results At 18.3 months median follow-up (range 1.8- 85.6 months), crude grade 2+ RP rates were 5.9% and 2.8% for patients with and without prior ALR, respectively (p=0.51), with 2-year estimates of freedom from RP of 89% and 97% (p=0.51). Crude rates of all grade 2+ pulmonary toxicity were 11.8% and 2.8% (p=0.11), respectively, with 2-year freedom from PT of 97% and 84%, (p=0.11). The 2 cohorts were well matched by mean lung dose, lung V20 (p=0.86) and prescribed dose (p=0.75). Two-year estimates of local control, cause-specific survival, and OS were similar between cohorts. Conclusions Observed rates of pulmonary toxicity were low among all patients, with a trend toward increased grade 2-3 lung toxicity among patients with prior ALR. Prior ALR did not increase risk of grade 4-5 RP, and SBRT appears safe and effective in this population. PMID:25737143

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Hypersensitivities to sesame and other common edible seeds.

    PubMed

    Patel, A; Bahna, S L

    2016-10-01

    Several seeds have been increasingly incorporated in various food items, with consequent risk of hypersensitivity reactions that are often severe. Identification of the specific seed as the culprit is often not explored or is difficult to verify. In this article, we reviewed the English literature from January 1930 to March 2016 using PubMed and Google Scholar searching for publications relevant to hypersensitivity to common edible seeds, namely sesame, sunflower seed, poppy seed, pumpkin seed, flaxseed, and mustard seed. Considering the worldwide consumption of those seeds, the number of published articles on the subject was relatively small and was mainly as case reports rather than large series. Allergy to sesame was more reported than to other seeds, with an estimated prevalence of 0.1-0.2%. In this review, we summarize the information relevant to each of the six seeds and their oils regarding the manifestations, routes of exposure, identified major allergens, and cross-reactivity with other seeds or other foods. We also addressed the important role of a thorough history taking in suspecting seed allergy, the limited reliability of routine diagnostic procedures, and the importance of verification by appropriate challenge tests. At present, management is basically dietary avoidance and the use of symptomatic medications that may include epinephrine auto-injectors. We did not encounter any well-designed studies on immunotherapy for seed allergy, but it is hoped that such a gap be filled by the development of safe effective protocols in the near future. PMID:27332789

  16. What we know about nonsteroidal anti-inflammatory drug hypersensitivity

    PubMed Central

    Pham, Duy Le; Kim, Ji-Hye; Trinh, Tu Hoang Kim; Park, Hae-Sim

    2016-01-01

    Nonsteroidal anti-inf lammatory drugs (NSAIDs) are widely prescribed for the treatment of inflammatory diseases, but their use is frequently related to hypersensitivity reactions. This review outlines our current knowledge of NSAID hypersensitivity (NHS) with regard to its pathogenic, molecular, and genetic mechanisms, as well as diagnosis and treatment. The presentation of NHS varies from a local (skin and/or airways) reaction to systemic reactions, including anaphylaxis. At the molecular level, NHS reactions can be classified as cross-reactive (mediated by cyclooxygenase inhibition) or selective (specific activation of immunoglobulin E antibodies or T cells). Genetic polymorphisms and epigenetic factors have been shown to be closely associated with NHS, and may be useful as predictive markers. To diagnose NHS, inhalation or oral challenge tests are applied, with the exclusion of any cross-reactive NSAIDs. For patients diagnosed with NHS, absolute avoidance of NSAIDs/aspirin is essential, and pharmacological treatment, including biologics, is often used to control their respiratory and cutaneous symptoms. Finally, desensitization is recommended only for selected patients with NHS. However, further research is required to develop new diagnostic methods and more effective treatments against NHS. PMID:27030979

  17. MinION: A Novel Tool for Predicting Drug Hypersensitivity?

    PubMed Central

    Chua, Eng Wee; Ng, Pei Yuen

    2016-01-01

    The launch of the MinION Access Program has caused much activity within the scientific community. MinION represents a keenly anticipated, novel addition to the current melange of commercial sequencers. Driven by the nanopore sequencing mechanism that requires minimal sample manipulation, the device is capable of generating long sequence reads in sizes (up to or exceeding 50 kb) that surpass those of all other platforms. One notable advantage of this feature is that long-range haplotypes can be more accurately resolved; such advantage is particularly pertinent to the genotyping of complex loci such as genes encoding the human leukocyte antigens, which are pivotal determinants of drug hypersensitivity. With this timely, albeit brief, review, we set out to examine the applications on which MinION has been tested thus far, the bioinformatics workflow tailored to the unique characteristics of its extended sequence reads, the device’s potential utility in the detection of genetic markers for drug hypersensitivity, and how it may eventually evolve to become fit for diagnostic purposes in the clinical setting. PMID:27378921

  18. Airway Inflammation and Hypersensitivity Induced by Chronic Smoking

    PubMed Central

    Kou, Yu Ru; Kwong, Kevin; Lee, Lu-Yuan

    2011-01-01

    Airway hypersensitivity, characterized by enhanced excitability of airway sensory nerves, is a prominent pathophysiological feature in patients with airway inflammatory diseases. Although the underlying pathogenic mechanism is not fully understood, chronic airway inflammation is believed to be primarily responsible. Cigarette smoking is known to cause chronic airway inflammation, accompanied by airway hyperresponsiveness. Experimental evidence indicates that enhanced excitability of vagal bronchopulmonary sensory nerves and increased tachykinin synthesis in these nerves resulting from chronic inflammation are important contributing factors to the airway hyperresponsiveness. Multiple inflammatory mediators released from various types of structural and inflammatory cells are involved in the smoking-induced airway inflammation, which is mainly regulated by redox-sensitive signaling pathways and transcription factors. Furthermore, recent studies have reported potent sensitizing and stimulatory effects of these inflammatory mediators such as prostanoids and reactive oxygen species on these sensory nerves. In summary, these studies using cigarette smoking as an experimental approach have identified certain potentially important cell signaling pathways and underlying mechanisms of the airway hypersensitivity induced by chronic airway inflammation. PMID:21397052

  19. [Delayed-type hypersensitivity to heparin: diagnosis and therapeutic management].

    PubMed

    Nosbaum, A; Pralong, P; Rozieres, A; Dargaud, Y; Nicolas, J-F; Bérard, F

    2012-05-01

    Heparin is widely used as an anticoagulant and is indicated in the prevention and treatment of thromboembolic disorders. Heparin-induced delayed-type hypersensitivity presents as eczematous lesions, either at the injection site or generally, and affects 7.5% of patients on heparin. This poses diagnostic and therapeutic issues, since an alternative anticoagulant treatment is essential and the risk of cross-reactivity may be as high as 80%, depending on the type of heparin used. If delayed-type hypersensitivity is suspected, heparin-induced thrombocytopenia must first be ruled out, and heparin should be stopped. Fondaparinux is currently the first-line alternative, with a risk of cross-reactivity estimated at only 10%. The switch from a low-molecular-weight heparin (LMWH) to another LMWH is no longer recommended. The use of unfractionated heparin, danaparoid or hirudin may be warranted in the event of recurrence with fondaparinux, and an immuno-allergological work-up is needed to specify the exact profile of cross-allergies. PMID:22578340

  20. CYSTIC FIBROSIS AND ANTIBIOTIC HYPERSENSITIVITY: PRESENT KNOWLEDGE AND PRACTICAL APPROACH.

    PubMed

    Caimmi, D; Chiron, R; Tremblay, F; Caimmi, S; Ricci, A; Licari, A; Marseglia, G L

    2015-01-01

    Cystic fibrosis is one of the most common fatal genetic diseases (1 in 2500 births). The defect causing the disease is localized on the 7q31 gene, which codifies for the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) transmembrane protein. CFTR is a chloride channel localized on the epithelial cells of the mucosa of the respiratory tract, pancreatic ducts, biliary tree, intestine, vas deferens and sweat glands. More than 2000 different mutations are currently known; some are prominent or relatively frequent, ranging from one population to another. The most frequent complications of cystic fibrosis are those affecting the bronchial tree. Patients suffer from recurrent lung infections, which involve a progressive loss of lung function. The pulmonary infections are frequent or chronic and limit the quality of life of patients. In addition to being enormously exposed to antibiotics, they have many more opportunities to develop hypersensitivity reactions to these molecules. Only a complete allergy work-up with a detailed analysis of the clinical history, skin tests and provocation test can show if the patient has actually experienced an allergic hypersensitivity reaction. Desensitization is to be considered as a treatment that may help patients benefit from antibiotic treatment in those cases in which they have a proven allergy to a certain molecule. PMID:26634585

  1. [The first and the second pneumonic plague in Manchuria and the preventive measure of Japanese colonial authorities (1910-1921)].

    PubMed

    Sihn, Kyu-Hwan

    2012-12-01

    During the first plague epidemic in Manchuria (1910-1911), Japanese Government-General in Korea had not reported a plague patient at all in official. This did not mean the preventive measure of colonial authorities was successful. Their prevention program and measure were operated inadequately. They focused on instigative and sometimes irrelevant aspects such as rat removal to restore order in the colony. The quarantine facility was insufficient so that some people could not be effectively isolated. The reason pneumonic plague did not spread from Manchuria to Korea was mostly because Chinese coolie did not enter Korea. The colonial government promulgated Jeonyeombyeong Yebangryeong (Preventive Regulation of Contagious Disease) in June 5, 1915. This regulation aimed at unitary control by police and was strengthened 10-day quarantine. After the March First Movement, the colonial government tried to change imperial policy to cultural policy. The military police and civilian police were bifurcated and governors took charge of health administration. However, sanitary police still played important role for preventive measure. The preventive policy of colonial government experienced important change from cholera epidemic between 1919 and 1920. The death toll of two years had exceeded 20,000 people. During the cholera outbreak of two years, quarantine and isolation were emerged as important tools to prevent disease transmission, and were well-appointed more now than before. To prevent cholera epidemic, the colonial government strengthened house-to-house inspection as well as seaport quarantine, train quarantine, passenger quarantine. House-to-house inspection detected sixty percentage of cholera patients. When the second Manchurian plague spread in Korea in 1920-1921, this plague was known to Korean people as pneumonic plague. The colonial government propagated and educated pneumonic plague, and urged to wear a mask through Heuksabyeong Yebang Simdeuk (The Notandum for

  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. An individual-based simulation of pneumonic plague transmission following an outbreak and the significance of intervention compliance.

    PubMed

    Williams, Andrew D C; Hall, Ian M; Rubin, G James; Amlôt, Richard; Leach, Steve

    2011-06-01

    The existence of primary pneumonic plague outbreaks raises concerns over the use of the causative bacteria as an aerosol-based bioweapon. We employed an individual-based model, parameterised using published personal contact information, to assess the severity of a deliberate release in a discrete community, under the influence of two proposed intervention strategies. We observed that the severity of the resulting epidemic is determined by the degree of personal compliance with said strategies, implying that prior preparedness activities are essential in order that public awareness and willingness to seek treatment is achieved quickly. PMID:21624780

  4. Hypersensitivity and pain induced by operative procedures and the "cracked tooth" syndrome.

    PubMed

    Seltzer, S; Boston, D

    1997-01-01

    Various dental conditions are responsible for tooth hypersensitivity and pain. They include hypersensitive dentin; the "cracked tooth" syndrome; pulp and periapical irritation, inflammation and/or degeneration; barodontalgia (aerodontalgia); and periodontal pathoses, particularly the pulpal-periodontal syndrome. Each operative condition is reviewed with respect to its etiology, symptomatology, and diagnosis. Some treatment recommendations are made to prevent or reduce symptoms.

  5. TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN MICE AFTER DERMAL AND INTRATRACHAEL (IT) EXPOSURES

    EPA Science Inventory

    ABSTRACT for 2001 DMS213

    TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN
    MICE AFTER DERMAL AND INTRATRACHEAL (IT) EXPOSURES. E Boykin, M Ward, MJ Selgrade, and D Sailstad. NHEERL, ORD, US EPA, RTP, NC, USA.
    TMA causes respiratory hypersensitivity (RH) responses. W...

  6. Successful desensitization protocol for hypersensitivity reaction probably caused by dabrafenib in a patient with metastatic melanoma.

    PubMed

    Bar-Sela, Gil; Abu-Amna, Mahmoud; Hadad, Salim; Haim, Nissim; Shahar, Eduardo

    2015-09-01

    Vemurafenib and dabrafenib are both orally bioavailable small molecule agents that block mitogen activated protein kinase signalling in patients with melanoma and BRAF(V600E) mutation. Generalized hypersensitivity reactions to vemurafenib or dabrafenib have not been described. Continuing vemurafenib or dabrafenib therapy despite hypersensitivity reaction is especially important in patients with melanoma and BRAF(V600E) mutation, in whom this mutation plays a critical role in tumour growth. Desensitization protocols to overcome hypersensitivity reactions by gradual reintroduction of small amounts of the offending drug up to full therapeutic doses are available for many anti-cancer agents, including vemurafenib but, to the best of our knowledge, have not been reported for dabrafenib. We describe a patient with metastatic melanoma who developed Type I hypersensitivity reaction to vemurafenib and to subsequent treatment with dabrafenib, and who was successfully treated by drug desensitization which allowed safe prolonged continuation of dabrafenib. The development of hypersensitivity reactions for both dabrafenib and vemurafinib in the current case could be because these drugs have a similar chemical structure and cause a cross-reactivity. However, hypersensitivity reaction to a non-medicinal ingredient shared by the two drugs is also possible. Oral desensitization appears to be an option for patients with hypersensitivity Type I to dabrafenib. This approach may permit clinicians to safely administer dabrafenib to patients who experience hypersensitivity reactions to this life-prolonging medication.

  7. Clinical efficacy of the Er:YAG laser treatment on hypersensitive dentin.

    PubMed

    Yu, Chuan-Hang; Chang, Yu-Chao

    2014-06-01

    Dentin hypersensitivity is a common symptomatic condition that causes discomfort and sometimes severe pain. The purpose of this study was to evaluate the clinical efficacy of the erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser treatment on cervically exposed hypersensitive dentin. Twenty patients with dentin hypersensitivity of caries-free teeth were selected. A visual analog scale (VAS) was used to measure dentin sensitivity in response to air stimulus. A 2-minute Er:YAG laser (energy level: 60 mJ/pulse; repetition rate: 2 Hz) was applied to cervically exposed hypersensitive dentin. After 4 weeks, the hypersensitive teeth were examined again, and the VAS score was measured again and recorded. No complications such as detrimental pulpal effects were observed. Eighteen participants reported significantly reduced dentin hypersensitivity 4 weeks after the laser desensitization treatment. The VAS scores measured 4 weeks after the Er:YAG laser desensitization treatment were significantly decreased as compared with those measured at the baseline (p < 0.05). In conclusion, the Er:YAG laser desensitization treatment can effectively reduce hypersensitivity of cervically exposed hypersensitive dentin. PMID:23602018

  8. Proper use of skin tests with food extracts in diagnosis of hypersensitivity to food in children.

    PubMed

    Bock, S A; Buckley, J; Holst, A; May, C D

    1977-07-01

    This study was undertaken to determine the proper use of skin tests with food extracts in diagnosis of hypersensitivity to food in children. Cutaneous reactions evoked by graded amounts of food extracts were compared with results of double-blind food challenge and in vitro release of histamine from leucocytes. A 3 mm or greater weal reaction in skin tests by puncture technique using food extracts of 1:20 w/v concentration was found to indicate the degree of hypersensitivity likely to be associated with clinically significant hypersensitivity reactions to food. Proper use of this simple technique will facilitate accurate diagnosis of food hypersensitivity in children by identifying the group among whom all positive reactions to food challenges will be found. Nevertheless, double-blind food challenge is essential to establish a diagnosis of symptomatic hypersensitivity to food.

  9. Milk as Desensitizing Agent for Treatment of Dentine Hypersensitivity Following Periodontal Treatment Procedures

    PubMed Central

    Sabir, Mohammad

    2015-01-01

    Background Dentinal hypersensitivity is a commonly observed problem after periodontal treatment procedures in periodontal patients. This further complicates preventive oral hygiene procedures by patients which jeopardize periodontal treatment, or even may aid in periodontal treatment failure. Aims and Objectives The aims and objectives of present study were to assess the problem of dentine hypersensitivity after non-surgical periodontal treatment and selection of cases for evaluation of commercially available milk at room temperature as mouth rinse for the treatment of dentinal hypersensitivity caused by periodontal treatment. Materials and Methods Patients were selected randomly for nonsurgical periodontal treatment and then were assessed for dentine hypersensitivity. Those having dentine hypersensitivity were assigned in two groups. Group one patients were advised to rinse with commercially available milk at room temperature, group two patients were advised to rinse with luke warm water as control. A four point Verbal Rating Score (VRS) was designed to record the numerical value of dentine hypersensitivity. Results The results show incidence of 42.5% and prevalence of 77.5% for dentine hypersensitivity after periodontal treatment procedures. After rinsing with milk following periodontal treatment procedures, there was found a significant reduction of dentine hypersensitivity with probability by unpaired t-test as 0.0007 and 0.0001 at tenth and fifteenth day post periodontal treatment procedures respectively. Conclusion This study demonstrated that the milk rinse is a suitable, cheaper, fast acting, home-use and easily available solution to the problem of dentine hypersensitivity after non-surgical periodontal treatment. Milk can be used as desensitizing agent and rinsing with milk for few days is effective in quick reduction of dentine hypersensitivity due to periodontal treatment procedures. PMID:26674005

  10. Examining the Latent Class Structure of CO2 Hypersensitivity using Time Course Trajectories of Panic Response Systems

    PubMed Central

    Roberson-Nay, Roxann; Beadel, Jessica R.; Gorlin, Eugenia I.; Latendresse, Shawn J.; Teachman, Bethany A.

    2014-01-01

    Background and Objectives Carbon dioxide (CO2) hypersensitivity is hypothesized to be a robust endophenotypic marker of panic spectrum vulnerability. The goal of the current study was to explore the latent class trajectories of three primary response systems theoretically associated with CO2 hypersensitivity: subjective anxiety, panic symptoms, and respiratory rate (fR). Methods Participants (n=376; 56% female) underwent a maintained 7.5% CO2 breathing task that included three phases: baseline, CO2 air breathing, and recovery. Growth mixture modeling was used to compare response classes (1..n) to identify the best-fit model for each marker. Panic correlates also were examined to determine class differences in panic vulnerability. Results For subjective anxiety ratings, a three-class model was selected, with individuals in one class reporting an acute increase in anxiety during 7.5% CO2 breathing and a return to pre-CO2 levels during recovery. A second, smaller latent class was distinguished by elevated anxiety across all three phases. The third class reported low anxiety reported during room air, a mild increase in anxiety during 7.5% CO2 breathing, and a return to baseline during recovery. Latent class trajectories for fR yielded one class whereas panic symptom response yielded two classes. Limitations This study examined CO2 hypersensitivity in one of the largest samples to date, but did not ascertain a general population sample thereby limiting generalizability. Moreover, a true resting baseline measure of fR was not measured. Conclusions Two classes potentially representing different risk pathways were observed. Implications of results will be discussed in the context of panic risk research. PMID:25496936

  11. Chronic prenatal stress epigenetically modifies spinal cord BDNF expression to induce sex specific visceral hypersensitivity in offspring

    PubMed Central

    Winston, John H.; Li, Qingjie; Sarna, Sushil K.

    2014-01-01

    Background Irritable bowel syndrome (IBS) is a heterogeneous disorder with abdomen pain as one of the primary symptoms. The etiology of IBS remains unknown. Epidemiological studies found that a subset of these patients have a history of adverse early-life events. We tested the hypothesis that chronic prenatal stress (CPS) epigenetically enhances brain-derived neurotrophic factor (BDNF) in spinal cord to aggravate colon sensitivity to colorectal distension (CRD) differentially in male and female offspring. Methods We used heterotypic intermittent chronic stress (HeICS) protocols in pregnant dams from E11 until delivery. Results CPS induced significant visceral hypersensitivity (VHS) to CRD in male and female offspring. A second exposure to HeICS in adult offspring exacerbated VHS greater in female offspring that persisted longer than in male offspring. CPS upregulated BDNF expression in the lumbar-sacral dorsal horn that correlated with the exacerbation of VHS in female, but not in male offspring. The upregulation of BDNF was due to a significant increase in RNA Pol II binding, histone H3 acetylation and significant decrease in histone deacetylase 1 association with the core promoter of BDNF in female offspring. Other chronic prenatal and neonatal stress protocols were less effective than HeICS. Conclusion & Inferences The development of visceral hypersensitivity, which contributes to the symptom of intermittent abdominal pain, is a two-step process, chronic in utero stress followed by chronic stress in adult-life. This two-step process induces aggravated and persistent colon hypersensitivity in female than in male offspring. Our preclinical model explains several clinical features in IBS patients. PMID:24588943

  12. Subjective Welfare, Well-Being, and Self-Reported Food Hypersensitivity in Four European Countries: Implications for European Policy

    ERIC Educational Resources Information Center

    Voordouw, Jantine; Antonides, Gerrit; Fox, Margaret; Cerecedo, Inmaculada; Zamora, Javier; de la Hoz Caballer, Belen; Rokicka, Ewa; Cornelisse-Vermaat, Judith; Jewczak, Maciej; Starosta, Pawel; Kowalska, Marek L.; Jedrzejczak-Czechowicz, Monika; Vazquez-Cortes, Sonia; Escudero, Cano; de Blok, Bertine Flokstra; Dubois, Anthony; Mugford, Miranda; Frewer, Lynn J.

    2012-01-01

    This study estimates the effects of food hypersensitivity on individuals' perceived welfare and well-being compared to non-food hypersensitive individuals. Study respondents were recruited in the Netherlands, Poland, Spain and UK. The difference in welfare between food hypersensitive respondents and those asymptomatic to foods was estimated using…

  13. 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

  14. 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

  15. 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

  16. Respiratory and oral vaccination improves protection conferred by the live vaccine strain against pneumonic tularemia in the rabbit model.

    PubMed

    Stinson, Elizabeth; Smith, Le'Kneitah P; Cole, Kelly Stefano; Barry, Eileen M; Reed, Douglas S

    2016-10-01

    Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge. PMID:27511964

  17. Respiratory and oral vaccination improves protection conferred by the live vaccine strain against pneumonic tularemia in the rabbit model.

    PubMed

    Stinson, Elizabeth; Smith, Le'Kneitah P; Cole, Kelly Stefano; Barry, Eileen M; Reed, Douglas S

    2016-10-01

    Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge.

  18. Hypersensitivity of Cockayne's syndrome cells to camptothecin is associated with the generation of abnormally high levels of double strand breaks in nascent DNA.

    PubMed

    Squires, S; Ryan, A J; Strutt, H L; Johnson, R T

    1993-05-01

    We report that fibroblasts from individuals with Cockayne's Syndrome (CS), an autosomal recessive disease exhibiting hypersensitivity to UV, are also hypersensitive to the killing action of camptothecin (CPT). In normal and CS cell lines the level of the protein-linked single strand DNA breaks (SSBs) induced by equal doses of CPT is similar, and these DNA breaks disappear within minutes of the removal of CPT. Thus, the toxicity of CPT does not correlate with the primary DNA lesions induced by the drug, and the hypersensitivity of CS cells cannot be explained by excessive topoisomerase I activity or by a defect in the enzyme ligation step. We have reported that CPT toxicity in normal cells is closely associated with the generation of double-strand DNA breaks (DSBs), predominantly at sites of DNA replication. The hypersensitivity of CS cells to CPT correlates closely with the much higher level of DSBs in nascent DNA than in normal cells. These DSBs are long-lived in all cells, but in CS many more (about 10-fold) remain 24 h after CPT removal and are presumably responsible for the higher frequency of chromosome aberrations in these cells. In CS as in normal cells aphidicolin prevents the generation of replication-related DSBs, suggesting that the movement of the DNA polymerase is necessary for the induction by CPT of the cytotoxic DSBs. Resistance to CPT and UV is restored to wild type in proliferating hybrids constructed between CS lines from two different complementation groups as is the abundance of replication-related DSBs. On the basis of this complementation we conclude that the UV and CPT sensitivities are distinct phenotypic traits arising from mutations in the CS A and B genes. PMID:7683249

  19. 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

  20. Astrometry of comets using hypersensitized type 2415 film

    NASA Technical Reports Server (NTRS)

    Everhart, E.

    1984-01-01

    Kodak Technical Pan Film 2415 should be known to those doing cometary astrometry. It has exceedingly fine resolution (320 lines/mm) and, when properly hypersensitized, it is almost as fast as treated IIIa-J plates and reaches fainter stars. Reciprocity failure with the treated film is practically zero, and the shelf life of treated film sheets is about a month at 2 C stored in a nitrogen atmosphere. This film is readily available in 4 by 5-inch sheets and is inexpensive. The film base is Estar, a plastic chosen for its stability. Over 120 astrometric measures of negatives on this film have shown a median residual error in comet positions of 1.1 seconds, a value that compares favorably with those of most observatories reporting positions.

  1. Fever, eosinophilia, and death: a case of minocycline hypersensitivity.

    PubMed

    Wu, Peggy A; Anadkat, Milan J

    2014-02-01

    Minocycline (MCN) is a member of the tetracycline family that is commonly used to treat dermatologic conditions such as acne and perioral dermatitis; however, it also has been associated with a number of adverse effects, including drug reaction with eosinophilia and systemic symptoms (DRESS). We report the case of a 46-year-old woman who developed a rash, fever, and eosinophilia during treatment with MCN for perioral dermatitis. Although MCN was discontinued and the patient was administered oral corticosteroids for several months, she subsequently died from multiorgan failure with giant cell myocardi-tis (GCM) and eosinophilic myocarditis found on autopsy. This article highlights a rare consequence of hypersensitivity to a commonly used drug and illustrates the importance of rapid recognition and aggressive management of MCN-induced DRESS.

  2. Drug Hypersensitivity Syndrome in a West-Indian population.

    PubMed

    Muller, Philippe; Dubreil, Patrick; Mahé, Antoine; Lamaury, Isabelle; Salzer, Birgit; Deloumeaux, Jacqueline; Strobel, Michel

    2003-01-01

    Some studies have suggested an ethnic susceptibility to Hypersensitivity Syndrome. We did a 7-year-prospective study in Guadeloupe whose population is mainly of African ancestry, and has free access to modern care facilities. Most patients included were Afro-Caribbeans (26/28), and females (20/28). However, ethnic distribution did not reach significant conclusions. Annual incidence rate was estimated at 0.9/100,000. Medium incubation and duration were 33 and 66 days respectively. Two patients with grade 4 hepatitis died from the syndrome. Two thirds of the patients were given prednisone, which usually alleviated the systemic symptoms, but did not prevent their development (in 5 patients) nor death. Carbamazepine, allopurinol, and minocycline accounted for 2/3 of the cases. Sixty four percent of the causative prescriptions were judged inappropriate. DHS appeared as the most frequent type of severe systemic drug reaction in this population, and may largely be prevented by rational prescribing.

  3. Hypersensitivity reactions to oxaliplatin and other antineoplastic agents.

    PubMed

    Syrigou, Ekaterini; Syrigos, Kostas; Saif, M Wasif

    2008-03-01

    Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is considered to be uncommon, it is difficult to evaluate their exact prevalence, mainly because their definition is vast and pathogenic mechanisms are vague. HSR include facial flushing, erythema, pruritus, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. Treatment and prevention consists of slowing the infusion rate, steroids, and type 1 and 2 histamine receptor antagonists. Desensitization could allow the small number of patients who experience severe HSR to receive effective therapy for their cancer. Reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitization strategies is still missing. With regard to oxaliplatin, knowledge of its rare but eminent toxicity is paramount, because this drug is widely used in treating colorectal cancer, the second-highest cause of cancer mortality in the United States. PMID:18377776

  4. Prevalence of latex hypersensitivity among health care workers in Malaysia.

    PubMed

    Shahnaz, M; Azizah, M R; Hasma, H; Mok, K L; Yip, E; Ganesapillai, T; Suraiya, H; Nasuruddin, B A

    1999-03-01

    Health care workers have been reported to constitute one of the few high-risk groups related to IgE-mediated hypersensitivity associated with the use of latex products. This paper describes the first ever study of prevalence carried out in Malaysia among these workers. One hundred and thirty health care personnel from Hospital Kuala Lumpur were skin tested. Extracts used were prepared from seven different brands of natural rubber latex gloves with varying levels of extractable protein (EPRRIM). Out of the 130 volunteers, 4 (3.1%) had positive skin test to latex with extracts with high levels of EPRRIM (> 0.7 mg/g). The prevalence among the Malaysian health care workers can be considered to be low in comparison to that of some consumer countries as the USA which reported a prevalence of as high as 16.9%.

  5. Quality of life in children and teenagers with food hypersensitivity.

    PubMed

    MacKenzie, Heather; Dean, Taraneh

    2010-08-01

    Given that food is essential for life and that there is currently no cure for food hypersensitivity (FHS), quality of life is a key outcome measure for those affected. The quality of life of children and teenagers with FHS is particularly important given that they must learn to manage their FHS while also contending with normal developmental challenges. This article will review the current state of quality of life research in this important area, and discusses the impact of FHS on the quality-of-life of children and teenagers, the availability and suitability of disease-specific health-related quality-of-life measures for this population, and the identification of factors that may influence their health-related quality of life. Two previous reviews have been conducted in this area, and this article aims to extend this work by including recent publications and qualitative studies on this topic.

  6. Efficacy of calcium sodium phosphosilicate in managing dentinal hypersensitivity.

    PubMed

    Surve, Sai M; Acharya, Anirudh B; Shetty, Ananya; Thakur, Srinath L

    2012-01-01

    A large number of home use products have been tested and used for managing dentinal hypersensitivity. This eight-week clinical trial compared the temporal efficacy of a commercially available toothpaste containing calcium sodium phosphosilicate to that of a toothpaste containing potassium nitrate. For this study, 20 subjects (age 18 - 65) were screened using a visual analog scale (VAS) for sensitivity to a cold stimulus. Baseline VAS sensitivity scores to tactile stimulus were recorded for a minimum of two teeth per patient. Dentifrices were prescribed for all patients and sensitivity scores were re-evaluated at two, four, and eight weeks. Though both groups showed significant reductions in sensitivity scores, only at eight weeks was there a marginally significant difference (p = 0.0551) in sensitivity scores between the test group and the positive control group. PMID:23032238

  7. HDAC4 is required for inflammation-associated thermal hypersensitivity

    PubMed Central

    Crow, Megan; Khovanov, Nikita; Kelleher, Jayne H.; Sharma, Simone; Grant, Andrew D.; Bogdanov, Yury; Wood, John N.; McMahon, Stephen B.; Denk, Franziska

    2015-01-01

    Transcriptional alterations are characteristic of persistent pain states, but the key regulators remain elusive. HDAC4 is a transcriptional corepressor that has been linked to synaptic plasticity and neuronal excitability, mechanisms that may be involved in peripheral and central sensitization. Using a conditional knockout (cKO) strategy in mice, we sought to determine whether the loss of HDAC4 would have implications for sensory neuron transcription and nociception. HDAC4 was found to be largely unnecessary for transcriptional regulation of naïve sensory neurons but was essential for appropriate transcriptional responses after injury, with Calca and Trpv1 expression consistently down-regulated in HDAC4 cKO compared to levels in the littermate controls (0.2–0.44-fold change, n = 4 in 2 separate experiments). This down-regulation corresponded to reduced sensitivity to 100 nM capsaicin in vitro (IC50 = 230 ± 20 nM, 76 ± 4.4% wild-type capsaicin responders vs. 56.9 ± 4.7% HDAC4 cKO responders) and to reduced thermal hypersensitivity in the complete Freund’s adjuvant (CFA) model of inflammatory pain (1.3–1.4-fold improvement over wild-type controls; n = 5–12, in 2 separate experiments). These data indicate that HDAC4 is a novel inflammatory pain mediator and may be a good therapeutic target, capable of orchestrating the regulation of multiple downstream effectors.—Crow, M., Khovanov, N., Kelleher, J. H., Sharma, S., Grant, A. D., Bogdanov, Y., Wood, J. N., McMahon, S. B., Denk, F. HDAC4 is required for inflammation-associated thermal hypersensitivity. PMID:25903105

  8. Food hypersensitivity among Caucasian and non-Caucasian children.

    PubMed

    Dias, Renuka P; Summerfield, Alison; Khakoo, G A

    2008-02-01

    There are little data regarding the frequency of different foods that cause hypersensitivity in the UK. Furthermore, there are no data regarding food hypersensitivity related to ethnic variations. This prospective study involved 76 children with IgE-mediated food allergy presenting consecutively over 18 months to a Paediatric Allergy Clinic serving a well-defined population that is 21% non-Caucasian. A total of 52.6% of the paediatric allergy clinic population was non-Caucasian compared with 35.9% in General Paediatric Clinics giving a mean difference in percentage of 16.7 (5.6, 27.8), p < 0.01. The average number of food allergens per child in the non-Caucasian group was 2.05 vs. 1.22 in the Caucasian group, mean difference 0.83, which is significant (t = 4.15, d.f. = 74, p < 0.01). Analysis of other allergic conditions revealed no significant increase in the non-Caucasian group. The mean age of first reaction to any food was 2.6 yr (range 0.3-12 yr) in Caucasian, and 1.7 yr (range 0.3-8 yr) in non-Caucasian, children (p < 0.05). There were 125 reactions in the study population, with egg, peanut, tree nut, cow milk and cod being the commonest food allergens. Some novel foods, such as kiwi, lentil and sesame, were also represented in the top 10 food allergies, particularly in the non-Caucasian population. Ethnic minorities are over-represented in terms of the number of children with food allergy and number of food allergies per child, present at an earlier age with food allergy, and possibly have a greater variety of food allergies compared with Caucasians. This is important in terms of health education. Our findings need confirmation by a more detailed population based study, ideally using food challenges in addition to history and skin prick testing.

  9. Irritable bowel syndrome in childhood: visceral hypersensitivity and psychosocial aspects.

    PubMed

    Iovino, P; Tremolaterra, F; Boccia, G; Miele, E; Ruju, F M; Staiano, A

    2009-09-01

    Visceral hypersensitivity is often considered to play a major etiologic role in the pathophysiology of irritable bowel syndrome in adults, and some authors argue that this increased sensitivity is mainly due to psychological factors. In contrast, there are no data in children with irritable bowel syndrome which confirm this relationship. The aim of the study was to evaluate the relationship between psychosocial aspects and sensorymotor function in children affected by irritable bowel syndrome. Ten children fulfilling the Rome II criteria for irritable bowel syndrome and seven healthy controls were enrolled. We studied the thresholds and the perception of visceral stimuli in the rectum by means of an electronic barostat (isobaric phasic distentions, 3 mmHg/1 min, interval 1 min) and a validated questionnaire. Personality features were evaluated by means of the Big Five Questionnaire for Children. Sleep, mood disturbance, anxiety and individual performance (missed school days, school results and social activities) were also evaluated. Children with irritable bowel syndrome showed significantly lower thresholds for discomfort (14.8 +/- 3.5 vs 22.3 +/- 6.9 mmHg, P = 0.010) and a higher cumulative perception score (28.2 +/- 11.1 vs 12.3 +/- 8.0, P = 0.005) compared with healthy controls. A higher emotional instability (57.8 +/- 7.0 vs 48.7 +/- 10.1, P = 0.047), sleep disturbance (7.2 +/- 1.0 vs 9.3 +/- 0.5, P = 0.004) and anxiety (6.3 +/- 2.0 vs 2.3 +/- 1.7, P = 0.009) were observed in irritable bowel syndrome patients. Moreover, in a multivariate analysis, the cumulative perception score was significantly related to emotional instability (P = 0.042). In conclusion children with irritable bowel syndrome exhibit visceral hypersensitivity and psychosocial impairment. Emotional instability, as a personality feature in these children, seems to modulate the perception response to visceral stimulations.

  10. Genetic factors in the predisposition to drug-induced hypersensitivity reactions.

    PubMed

    Pirmohamed, Munir

    2006-02-03

    Drug hypersensitivity reactions can occur with most drugs, although the frequency, severity, and clinical manifestations vary. Case reports have suggested that there may be familial clustering of drug hypersensitivity suggesting a genetic predisposition. As with most other forms of drug response, predisposition to drug hypersensitivity reactions is likely to be multifactorial and multigenic. Given the immune pathogenesis of these reactions, it is perhaps not surprising that the most significant genetic associations have been identified in the major histocompatibility complex for drugs such as abacavir, carbamazepine, and allopurinol. For abacavir, it has been suggested that preprescription genotyping for HLA-B*5701 in whites may reduce the incidence of hypersensitivity. It is likely that as our knowledge of variation in the human genome improves, coupled with improvements in technology, many more significant genetic predisposing factors for drug hypersensitivity are likely to be identified in the next decade. However, as we search for these genetic factors, it is important that we do not forget environmental predisposition, and to bear in mind that a genetic marker for drug hypersensitivity in one population may not necessarily be relevant for another population. Notwithstanding the advances in genetic technologies, the ultimate determinant of success in this area of research will be the identification and careful phenotyping of patients with drug hypersensitivity reactions. As we progress to whole genome scanning, in order to satisfy the requirements for adequate statistical power, the identification of large numbers of carefully phenotyped patients will be feasible only through international collaborations.

  11. Acceptor sites for retroviral integrations map near DNase I-hypersensitive sites in chromatin.

    PubMed Central

    Vijaya, S; Steffen, D L; Robinson, H L

    1986-01-01

    Seven cellular loci with acceptor sites for retroviral integrations have been mapped for the presence of DNase I-hypersensitive sites in chromatin. Integrations in three of these loci, chicken c-erbB, rat c-myc, and a rat locus, dsi-1, had been selected for in retrovirus-induced tumors. Of the remaining four, two, designated dsi-3 and dsi-4, harbored acceptor sites for apparently unselected integrations of Moloney murine leukemia virus in a Moloney murine leukemia virus-induced thymoma, and two, designated C and F, harbored unselected acceptor sites for Moloney murine leukemia virus integrations in a rat fibroblast cell line. Each acceptor site mapped to within 500 base pairs of a DNase I-hypersensitive site. In the analyses of the unselected integrations, six hypersensitive sites were observed in 39 kilobases of DNA. The four acceptor sites in this DNA were localized between 0.05 and 0.43 kilobases of a hypersensitive site. The probability of this close association occurring by chance was calculated to be extremely low. Hypersensitive sites were mapped in cells representing the lineage in which integration had occurred as well as in an unrelated lineage. In six of the seven acceptor loci hypersensitive sites could not be detected in the unrelated lineage. Our results indicate that retroviruses preferentially integrate close to DNase I-hypersensitive sites and that many of these sites are expressed in some but not all cells. Images PMID:3490582

  12. The excitatory amino acid receptor antagonist MK-801 prevents the hypersensitivity induced by spinal cord ischemia in the rat

    SciTech Connect

    Hao, J.X.; Xu, X.J.; Aldskogius, H.; Seiger, A.; Wiesenfeld-Hallin, Z. )

    1991-08-01

    Protection by the NMDA receptor antagonist MK-801 against transient spinal cord ischemia-induced hypersensitivity was studied in rats. The spinal ischemia was initiated by vascular occlusion resulting from the interaction between the photosensitizing dye Erythrosin B and an argon laser beam. The hypersensitivity, termed allodynia, where the animals reacted by vocalization to nonnoxious mechanical stimuli in the flank area, was consistently observed during several days after induction of the ischemia. Pretreatment with MK-801 (0.1-0.5 mg/kg, iv) 10 min before laser irradiation dose dependently prevented the occurrence of allodynia. The neuroprotective effect of MK-801 was not reduced by maintaining normal body temperature during and after irradiation. There was a significant negative correlation between the delay in the administration of MK-801 after irradiation and the protective effect of the drug. Histological examination revealed slight morphological damage in the spinal cord in 38% of control rats after 1 min of laser irradiation without pretreatment with MK-801. No morphological abnormalities were observed in rats after pretreatment with MK-801 (0.5 mg/kg). The present results provide further evidence for the involvement of excitatory amino acids, through activation of the NMDA receptor, in the development of dysfunction following ischemic trauma to the spinal cord.

  13. Cervical dentin hypersensitivity: a cross-sectional investigation in Athens, Greece.

    PubMed

    Rahiotis, C; Polychronopoulou, A; Tsiklakis, K; Kakaboura, A

    2013-12-01

    The purpose of this study was to identify the prevalence of cervical dentin hypersensitivity in a cross-sectional investigation of Greek adults. Seven hundred and sixty-seven subjects were examined. Participants were patients processed for first examination in the Clinic of Oral Diagnosis and Radiology at the Faculty of Dentistry, University of Athens. The evaluation of hypersensitivity was performed using two methods: for each tooth, the response to a) tactile stimulus and b) air-blast stimulus was measured. Additional factors such as smoking habits, oral health behaviour, consumption of acidic foods, type of toothbrush, daily use of fluoride solution and of desensitising toothpaste, gingival recession and non-carious cervical lesions were recorded and evaluated as causative factors. Descriptive statistics on the demographics of the study sample, of oral health behaviour characteristics and of oral examination findings were performed. Comparisons of these characteristics in the presence or absence of hypersensitivity were conducted with the chi-square test. Data were further analysed using multiple logistic regression modelling. Among study participants, 21·3% had at least one cervical dentin hypersensitivity reaction to the tactile stimulus, and 38·6%, to the air-blast stimulus. Multivariate analysis detected association of the hypersensitivity in tactile or air-blast stimulus with the non-carious lesions and with the gingival recessions. Additionally, a relation between hypersensitivity and air-blast stimulus with gender (female) was found. There was no association between the hypersensitivity in both of the stimuli and the level of education, smoking, consumption of acidic foods, type of toothbrush and daily use of fluoride solution or desensitising toothpaste. The overall prevalence of cervical dentin hypersensitivity in the adult population in Athens ranged from 21·3% to 38·6% depending on the type of stimuli. Cervical non-carious lesions and gingival

  14. Hypersensitivity Vasculitis with Leukocytoclastic Vasculitis Associated with Alpha-1-Proteinase Inhibitor

    PubMed Central

    Mwirigi, Nicola W.; Thomas, Charles F.

    2009-01-01

    Prolastin is a commercially available form of alpha-1-antitrypsin (AAT) that is derived from pooled human plasma and used for treatment of severe alpha-1-antitrypsin deficiency (AATD). We describe a patient with AATD who developed presumed hypersensitivity vasculitis (HV) following a Prolastin infusion. Hypersensitivity vasculitis (HV), or cutaneous vasculitis, is characterized by inflammation of the small vessels of the skin with resultant ischemia to the distally supplied areas. To our knowledge, this is the first reported case of presumed hypersensitivity vasculitis following Prolastin infusion. PMID:20204065

  15. Pharmacological characterization of standard analgesics on oxaliplatin-induced acute cold hypersensitivity in mice.

    PubMed

    Zhao, Meng; Nakamura, Saki; Miyake, Takahito; So, Kanako; Shirakawa, Hisashi; Tokuyama, Shogo; Narita, Minoru; Nakagawa, Takayuki; Kaneko, Shuji

    2014-01-01

    Oxaliplatin, a platinum-based chemotherapeutic agent, causes an acute peripheral neuropathy triggered by cold in almost all patients during or within hours after its infusion. We recently reported that a single administration of oxaliplatin induced cold hypersensitivity 2 h after the administration in mice. In this study, we examined whether standard analgesics relieve the oxaliplatin-induced acute cold hypersensitivity. Gabapentin, tramadol, mexiletine, and calcium gluconate significantly inhibited and morphine and milnacipran decreased the acute cold hypersensitivity, while diclofenac and amitriptyline had no effects. These results suggest that gabapentin, tramadol, mexiletine, and calcium gluconate are effective against oxaliplatin-induced acute peripheral neuropathy. PMID:24671055

  16. Uncertainty analysis of diffuse-gray radiation enclosure problems: A hypersensitive case study

    NASA Technical Reports Server (NTRS)

    Taylor, Robert P.; Luck, Rogelio; Hodge, B. K.; Steele, W. Glenn

    1993-01-01

    An uncertainty analysis of diffuse-gray enclosure problems is presented. The genesis was a diffuse-gray enclosure problem which proved to be hypersensitive to the specification of view factors. This genesis is discussed in some detail. The uncertainty analysis is presented for the general diffuse-gray enclosure problem and applied to the hypersensitive case study. It was found that the hypersensitivity could be greatly reduced by enforcing both closure and reciprocity for the view factors. The effects of uncertainties in the surface emissivities and temperatures are also investigated.

  17. A plague on five of your houses - statistical re-assessment of three pneumonic plague outbreaks that occurred in Suffolk, England, between 1906 and 1918

    PubMed Central

    2010-01-01

    Background Plague is a re-emerging disease and its pneumonic form is a high priority bio-terrorist threat. Epidemiologists have previously analysed historical outbreaks of pneumonic plague to better understand the dynamics of infection, transmission and control. This study examines 3 relatively unknown outbreaks of pneumonic plague that occurred in Suffolk, England, during the first 2 decades of the twentieth century. Methods The Kolmogorov-Smirnov statistical test is used to compare the symptomatic period and the length of time between successive cases (i.e. the serial interval) with previously reported values. Consideration is also given to the case fatality ratio, the average number of secondary cases resulting from each primary case in the observed minor outbreaks (termed Rminor), and the proportion of individuals living within an affected household that succumb to pneumonic plague via the index case (i.e. the household secondary attack rate (SAR)). Results 2 of the 14 cases survived giving a case fatality ratio of 86% (95% confidence interval (CI) = {57%, 98%}). For the 12 fatal cases, the average symptomatic period was 3.3 days (standard deviation (SD) = 1.2 days) and, for the 11 non index cases, the average serial interval was 5.8 days (SD = 2.0 days). Rminor was calculated to be 0.9 (SD = 1.0) and, in 2 households, the SAR was approximately 14% (95% CI = {0%, 58%}) and 20% (95% CI = {1%, 72%}), respectively. Conclusions The symptomatic period was approximately 1 day longer on average than in an earlier study but the serial interval was in close agreement with 2 previously reported values. 2 of the 3 outbreaks ended without explicit public health interventions; however, non-professional caregivers were particularly vulnerable - an important public health consideration for any future outbreak of pneumonic plague. PMID:20973955

  18. PCR assay detects Mannheimia haemolytica in culture-negative pneumonic lung tissues of bighorn sheep (Ovis canadensis) from outbreaks in the western USA, 2009-2010.

    PubMed

    Shanthalingam, Sudarvili; Goldy, Andrea; Bavananthasivam, Jegarubee; Subramaniam, Renuka; Batra, Sai Arun; Kugadas, Abirami; Raghavan, Bindu; Dassanayake, Rohana P; Jennings-Gaines, Jessica E; Killion, Halcyon J; Edwards, William H; Ramsey, Jennifer M; Anderson, Neil J; Wolff, Peregrine L; Mansfield, Kristin; Bruning, Darren; Srikumaran, Subramaniam

    2014-01-01

    Mannheimia haemolytica consistently causes severe bronchopneumonia and rapid death of bighorn sheep (Ovis canadensis) under experimental conditions. However, Bibersteinia trehalosi and Pasteurella multocida have been isolated from pneumonic bighorn lung tissues more frequently than M. haemolytica by culture-based methods. We hypothesized that assays more sensitive than culture would detect M. haemolytica in pneumonic lung tissues more accurately. Therefore, our first objective was to develop a PCR assay specific for M. haemolytica and use it to determine if this organism was present in the pneumonic lungs of bighorns during the 2009-2010 outbreaks in Montana, Nevada, and Washington, USA. Mannheimia haemolytica was detected by the species-specific PCR assay in 77% of archived pneumonic lung tissues that were negative by culture. Leukotoxin-negative M. haemolytica does not cause fatal pneumonia in bighorns. Therefore, our second objective was to determine if the leukotoxin gene was also present in the lung tissues as a means of determining the leukotoxicity of M. haemolytica that were present in the lungs. The leukotoxin-specific PCR assay detected leukotoxin gene in 91% of lung tissues that were negative for M. haemolytica by culture. Mycoplasma ovipneumoniae, an organism associated with bighorn pneumonia, was detected in 65% of pneumonic bighorn lung tissues by PCR or culture. A PCR assessment of distribution of these pathogens in the nasopharynx of healthy bighorns from populations that did not experience an all-age die-off in the past 20 yr revealed that M. ovipneumoniae was present in 31% of the animals whereas leukotoxin-positive M. haemolytica was present in only 4%. Taken together, these results indicate that culture-based methods are not reliable for detection of M. haemolytica and that leukotoxin-positive M. haemolytica was a predominant etiologic agent of the pneumonia outbreaks of 2009-2010.

  19. Deletion of Braun lipoprotein and plasminogen-activating protease-encoding genes attenuates Yersinia pestis in mouse models of bubonic and pneumonic plague.

    PubMed

    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; Chopra, Ashok K

    2014-06-01

    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.

  20. 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.

  1. An atypical PMR2 locus is responsible for hypersensitivity to sodium and lithium cations in the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D.

    PubMed

    Daran-Lapujade, Pascale; Daran, Jean-Marc; Luttik, Marijke A H; Almering, Marinka J H; Pronk, Jack T; Kötter, Peter

    2009-08-01

    Saccharomyces cerevisiae strains belonging to the CEN.PK family are widely used in fundamental and applied yeast research. These strains have been reported to be hypersensitive to sodium ions and a previous microarray-based genotyping study indicated an atypical organization of the PMR2 locus. In other S. cerevisiae strains, this locus harbours one to five ENA genes that encode plasma membrane sodium-pumping ATPases. Sequence analysis of the PMR2 locus in S. cerevisiae CEN.PK113-7D revealed the presence of a new ENA gene that showed substantial sequence differences, both at the nucleotide level and at the predicted amino acid sequence level, with previously described ENA genes. The presence of this single and atypical ENA gene correlated with hypersensitivity to sodium and, in particular, to lithium ions. The native ENA6 gene was transcriptionally induced by sodium and lithium ions, but, apparently, the capacity for sodium export upon full induction was insufficient to achieve the levels of sodium and lithium ion tolerance observed in other S. cerevisiae strains. The sodium and lithium hypersensitivity of CEN.PK strains, which is potentially detrimental during cultivation in sodium-rich media, could, however, be suppressed by overexpression of ENA6.

  2. Computerized cuff pressure algometry: A new method to assess deep-tissue hypersensitivity in fibromyalgia.

    PubMed

    Jespersen, Anders; Dreyer, Lene; Kendall, Sally; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars; Bliddal, Henning; Danneskiold-Samsoe, Bente

    2007-09-01

    The aim of this study was to evaluate the use of computerized cuff pressure algometry (CPA) in fibromyalgia (FM) and to correlate deep-tissue sensitivity assessed by CPA with other disease markers of FM. Forty-eight women with FM and 16 healthy age-matched women were included. A computer-controlled, pneumatic tourniquet cuff was placed over the gastrocnemius muscle. The cuff was inflated, and the subject rated the pain intensity continuously on an electronic Visual Analogue Scale (VAS). The subject stopped the inflation at the pressure-pain tolerance and the corresponding VAS-score was determined (pressure-pain limit). The pressure at which VAS firstly exceeded 0 was defined as the pressure-pain threshold. Other disease markers (FM only): Isokinetic knee muscle strength, tenderpoint-count, myalgic score, Beck Depression Inventory, and Fibromyalgia Impact Questionnaire. Student's T-test was used to compare pressure-pain threshold and pressure-pain tolerance and the Mann-Whitney test to compare pressure-pain limit. Pearson's correlation was used to detect linear relationships. Pressure-pain threshold and pressure-pain tolerance assessed by CPA were significantly lower in FM compared to healthy controls. There was no difference in pressure-pain limit. CPA-parameters were significantly correlated to isokinetic muscle strength where more hypersensitivity resulted in lower strength. Pressure-pain threshold and pressure-pain tolerance assessed by CPA were significantly lower in patients with FM indicating muscle hyperalgesia. CPA was associated with knee muscle strength but not with measures thought to be influenced by psychological distress and mood.

  3. The Phytoalexin Resveratrol Regulates the Initiation of Hypersensitive Cell Death in Vitis Cell

    PubMed Central

    Chang, Xiaoli; Heene, Ernst; Qiao, Fei; Nick, Peter

    2011-01-01

    Resveratrol is a major phytoalexin produced by plants in response to various stresses and promotes disease resistance. The resistance of North American grapevine Vitis rupestris is correlated with a hypersensitive reaction (HR), while susceptible European Vitis vinifera cv. ‘Pinot Noir’ does not exhibit HR, but expresses basal defence. We have shown previously that in cell lines derived from the two Vitis species, the bacterial effector Harpin induced a rapid and sensitive accumulation of stilbene synthase (StSy) transcripts, followed by massive cell death in V. rupestris. In the present work, we analysed the function of the phytoalexin resveratrol, the product of StSy. We found that cv. ‘Pinot Noir’ accumulated low resveratrol and its glycoside trans-piceid, whereas V. rupestris produced massive trans-resveratrol and the toxic oxidative δ-viniferin, indicating that the preferred metabolitism of resveratrol plays role in Vitis resistance. Cellular responses to resveratrol included rapid alkalinisation, accumulation of pathogenesis-related protein 5 (PR5) transcripts, oxidative burst, actin bundling, and cell death. Microtubule disruption and induction of StSy were triggered by Harpin, but not by resveratrol. Whereas most responses proceeded with different amplitude for the two cell lines, the accumulation of resveratrol, and the competence for resveratrol-induced oxidative burst differed in quality. The data lead to a model, where resveratrol, in addition to its classical role as antimicrobial phytoalexin, represents an important regulator for initiation of HR-related cell death. PMID:22053190

  4. Short Telomeres Result in Organismal Hypersensitivity to Ionizing Radiation in Mammals

    PubMed Central

    Goytisolo, Fermín A.; Samper, Enrique; Martín-Caballero, Juan; Finnon, Paul; Herrera, Eloísa; Flores, Juana M.; Bouffler, Simon D.; Blasco, María A.

    2000-01-01

    Here we show a correlation between telomere length and organismal sensitivity to ionizing radiation (IR) in mammals. In particular, fifth generation (G5) mouse telomerase RNA (mTR)−/− mice, with telomeres 40% shorter than in wild-type mice, are hypersensitive to cumulative doses of gamma rays. 60% of the irradiated G5 mTR−/− mice die of acute radiation toxicity in the gastrointestinal tract, lymphoid organs, and kidney. The affected G5 mTR−/− mice show higher chromosomal damage and greater apoptosis than similarly irradiated wild-type controls. Furthermore, we show that G5 mTR−/− mice show normal frequencies of sister chromatid exchange and normal V(D)J recombination, suggesting that short telomeres do not significantly affect the efficiency of DNA double strand break repair in mammals. The IR-sensitive phenotype of G5 mTR−/− mice suggests that telomere function is one of the determinants of radiation sensitivity of whole animals. PMID:11104804

  5. DNase I hypersensitivity mapping and promoter polymorphism analysis of human C4

    SciTech Connect

    Vaishnaw, A.K.; Hargreaves, R.; Morley, B.J.

    1995-04-01

    Human complement component C4 is encoded by two structurally distinct loci in the major histocompatibility complex (MHC) class III region. The two isotypes, C4A and C4B, differ at only four residues in the C4d fragment, but C4 constitutes the most polymorphic of the complement components. It is not known, however, whether the regions involved in the regulation of C4 expression also display polymorphic variation. By using the technique of DNase I hypersensitivity mapping, we established that the only area of transcriptional activity for C4 in the hepatocyte cell line, HepG2, occurs approximately 500 base pairs upstream of the transcriptional start site. This region was found to be remarkably constant in sequence when analyzed in the context of differing MHC haplotypes including HLA B57, C4A6, C4B1, DR7, which has been correlated with reduced expression of the C4A isotype. Similarly, polymerase chain reaction followed by single-strand conformation polymorphism analysis failed to demonstrate any promoter polymorphisms in 103 individuals comprising 52 systemic lupus erythermatosus patients and 51 healthy controls. 36 refs., 3 figs., 2 tabs.

  6. Development and evaluation of an electromagnetic hypersensitivity questionnaire for Japanese people.

    PubMed

    Hojo, Sachiko; Tokiya, Mikiko; Mizuki, Masami; Miyata, Mikio; Kanatani, Kumiko T; Takagi, Airi; Tsurikisawa, Naomi; Kame, Setsuko; Katoh, Takahiko; Tsujiuchi, Takuya; Kumano, Hiroaki

    2016-09-01

    The purpose of the present study was to evaluate the validity and reliability of a Japanese version of an electromagnetic hypersensitivity (EHS) questionnaire, originally developed by Eltiti et al. in the United Kingdom. Using this Japanese EHS questionnaire, surveys were conducted on 1306 controls and 127 self-selected EHS subjects in Japan. Principal component analysis of controls revealed eight principal symptom groups, namely, nervous, skin-related, head-related, auditory and vestibular, musculoskeletal, allergy-related, sensory, and heart/chest-related. The reliability of the Japanese EHS questionnaire was confirmed by high to moderate intraclass correlation coefficients in a test-retest analysis, and high Cronbach's α coefficients (0.853-0.953) from each subscale. A comparison of scores of each subscale between self-selected EHS subjects and age- and sex-matched controls using bivariate logistic regression analysis, Mann-Whitney U- and χ(2) tests, verified the validity of the questionnaire. This study demonstrated that the Japanese EHS questionnaire is reliable and valid, and can be used for surveillance of EHS individuals in Japan. Furthermore, based on multiple logistic regression and receiver operating characteristic analyses, we propose specific preliminary criteria for screening EHS individuals in Japan. Bioelectromagnetics. 37:353-372, 2016. © 2016 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc. PMID:27324106

  7. Delayed Hypersensitivity: Indicator of Acquired Failure of Host Defenses in Sepsis and Trauma

    PubMed Central

    Meakins, Jonathan L.; Pietsch, John B.; Bubenick, Oldrich; Kelly, Ralph; Rode, Harold; Gordon, Julius; MacLean, Lloyd D.

    1977-01-01

    Primary failure of host defense mechanisms has been associated with increased infection and mortality. Anergy, the failure of delayed hypersensitivity response, has been shown to identify surgical patients at increased risk for sepsis and related mortality. The anergic and relatively anergic patients whose skin tests failed to improve had a mortality rate of 74.4%, whereas those who improved their responses had a mortality rate of 5.1% (P < 0.001). This study documents abnormalities of neutrophil chemotaxis, T-lymphocyte rosetting in anergic patients and the effect of autologous serum. These abnormalities may account for the increased infection and mortality rates in anergic patients. Skin testing with five standard antigens has identified 110 anergic (A) or relatively anergic (RA) patients in whom neutrophil chemotaxis (CTX) and bactericidal function (NBF), T-lymphocyte rosettes, mixed lymphocyte culture (MLC), cell-mediated lympholysis (CML), and blastogenic factor (BF) were studied. The MLC, CML and BF were normal in the patients studied, and were not clinically helpful. Neutrophil CTX in 19 controls was 117.5 ± 1.6 u whereas in 40 A patients, neutrophils migrated 81.7 ± 2.3 u and in 15 RA patients 97.2 ± 3.8 u (P < 0.01). In 14 patients whose skin tests converted to normal, neutrophil migration improved from 78.2 ± 5.4 u to 107.2 ± 4.0 u (P < 0.01). Incubation of A or control neutrophils in A serum reduced migration in A patients from 93 ± 3.7 u to 86.2 ± 3.5 u (P < 0.01) and in normals from 121.2 ± 1.6 u to 103.6 ± 2.6 u (P < 0.001). The per cent rosette forming cells in 66 A patients was 42.5 ± 3.1 compared to 53.6 ± 2.8 in normal responders (P < 0.02). Incubation of normal lymphocytes in anergic serum further reduced rosetting by 30%. Restoration of delayed hypersensitivity responses and concurrent improvement in cellular and serum components of host defense were correlated with maintenance of adequate nutrition and aggressive surgical drainage

  8. Electroacupuncture at He-Mu points reduces P2X4 receptor expression in visceral hypersensitivity.

    PubMed

    Guo, Xinxin; Chen, Jifei; Lu, Yuan; Wu, Luyi; Weng, Zhijun; Yang, Ling; Xin, Yuhu; Lin, Xianming; Liang, Yi; Fang, Jianqiao

    2013-08-01

    Electroacupuncture at Shangjuxu (ST37) and Tianshu (ST25) was reported to improve visceral hypersensitivity in rats. Colorectal distension was utilized to generate a rat model of chronic visceral hypersensitivity in irritable bowel syndrome. Results showed that abdominal withdrawal reflex scores noticeably increased after model establishment. Simultaneously, P2X4 receptor immureactivity significantly increased in the colon and spinal cord. Electroacupuncture and pinaverium bromide therapy both markedly decreased abdominal withdrawal reflex scores in rats with visceral hypersensitivity, and significantly decreased P2X4 receptor immunoreactivity in the colon and spinal cord. These data suggest that electroacupuncture treatment can improve visceral hypersensitivity in rats with irritable bowel syndrome by diminishing P2X4 receptor immunoreactivity in the colon and spinal cord. PMID:25206515

  9. Electroacupuncture at He-Mu points reduces P2X4 receptor expression in visceral hypersensitivity

    PubMed Central

    Guo, Xinxin; Chen, Jifei; Lu, Yuan; Wu, Luyi; Weng, Zhijun; Yang, Ling; Xin, Yuhu; Lin, Xianming; Liang, Yi; Fang, Jianqiao

    2013-01-01

    Electroacupuncture at Shangjuxu (ST37) and Tianshu (ST25) was reported to improve visceral hypersensitivity in rats. Colorectal distension was utilized to generate a rat model of chronic visceral hypersensitivity in irritable bowel syndrome. Results showed that abdominal withdrawal reflex scores noticeably increased after model establishment. Simultaneously, P2X4 receptor immureactivity significantly increased in the colon and spinal cord. Electroacupuncture and pinaverium bromide therapy both markedly decreased abdominal withdrawal reflex scores in rats with visceral hypersensitivity, and significantly decreased P2X4 receptor immunoreactivity in the colon and spinal cord. These data suggest that electroacupuncture treatment can improve visceral hypersensitivity in rats with irritable bowel syndrome by diminishing P2X4 receptor immunoreactivity in the colon and spinal cord. PMID:25206515

  10. Sulfa hypersensitivity in patients with HIV infection: onset, treatment, critical review of the literature.

    PubMed

    Ryan, C; Madalon, M; Wortham, D W; Graziano, F M

    1998-05-01

    Trimethoprim/Sulfamethoxazole is the most effective medication used in both the treatment and prevention of Pneumocystis carinii pneumonia (PCP) in patients with HIV/AIDS. Its use, however, is accompanied by a high incidence of adverse reactions, especially fever, myalgia and rash (sulfa hypersensitivity). In a group of our patients, we have examined the clinical parameters at the time of onset of sulfa hypersensitivity, and the success of a desensitization protocol for this adverse event. We also have performed a comprehensive review of the literature on sulfa hypersensitivity and have compared our results to those previously reported in the literature. Our findings indicate that the sulfa hypersensitivity reaction is more likely to develop in patients with advanced disease and that desensitization can restore tolerability to the drug in approximately two thirds of those who attempt it.

  11. Neural Mechanisms Involved in Hypersensitive Hearing: Helping Children with ASD Who Are Overly Sensitive to Sounds

    PubMed Central

    Lucker, Jay R.; Doman, Alex

    2015-01-01

    Professionals working with children diagnosed with autism spectrum disorder (ASD) may find that these children are overly sensitive to sounds. These professionals are often concerned as to why children may have auditory hypersensitivities. This review article discusses the neural mechanisms identified underlying hypersensitive hearing in people. The authors focus on brain research to support the idea of the nonclassical auditory pathways being involved in connecting the auditory system with the emotional system of the brain. The authors also discuss brain mechanisms felt to be involved in auditory hypersensitivity. The authors conclude with a discussion of some treatments for hypersensitive hearing. These treatments include desensitization training and the use of listening therapies such as The Listening Program. PMID:26823983

  12. [Utility of challenge test in immediate hypersensitivity to hydrocortisone sodium succinate].

    PubMed

    Amaya-Mejía, Adela Sisy; Galindo-Pacheco, Lucy Vania; O'Farrill-Romanillos, Patricia María; Rodríguez-Mireles, Karen Alicia; Campos-Romero, Freya Helena; del Rivero-Hernández, Leonel

    2014-01-01

    Corticosteroid hypersensitivity is a complex phenomenon in which many factors interact, such as idiosyncrasy, intolerance or allergic reactions. The prevalence of immediate hypersensitivity reactions to corticosteroids is 0.2%-0.5%. Corticosteroids have major therapeutic implications; thus, when hypersensitivity is suspected, in-vitro and/or in-vivo testing can be performed to confirm diagnosis, being the drug challenge the gold standard. After definitive diagnosis, cross-reactivity among the different corticosteroid groups should be considered, to choose wisely if corticosteroid therapy is still required. In Coopman classification, steroids belonging to groups A, B and D2 have high cross-reactivity, however, more studies are needed to determine the degree of cross-reaction among these drugs. This paper presents the case of a woman, in who hypersensitivity to hydrocortisone succinate was confirmed by drug challenge test.

  13. Hypersensitivity reactions to vaccine constituents: a case series and review of the literature.

    PubMed

    Leventhal, Jonathan S; Berger, Emily M; Brauer, Jeremy A; Cohen, David E

    2012-01-01

    Vaccines are composed of immunogens, preservatives, adjuvants, antibiotics, and manufacturing by-products. Components of vaccines may rarely elicit adverse reactions in susceptible individuals, thus raising concerns regarding vaccine safety. In this report, we add to the medical literature 3 cases of cutaneous delayed-type hypersensitivity to the vaccine preservative aluminum. We provide a review of major constituents in vaccines that have elicited immediate-type or delayed-type hypersensitivity reactions and describe their clinical manifestations. We include a table of the Food and Drug Administration-approved vaccines, which lists the quantities of major components including ovalbumin (egg protein), gelatin, aluminum, neomycin, 2-phenoxyethanol, thimerosal, and formaldehyde. Our goals were to inform physicians on the variety of hypersensitivity reactions to common vaccines and to provide information on the choice of vaccines in patients with suspected hypersensitivity.

  14. [Corneal ulcerative lesions in type-I immediate hypersensitivity].

    PubMed

    Giuri, S

    1998-01-01

    The vernal keratoconjunctivitis (KCV) is included within the category of the hypersensitiveness diseases, the immunopathological mechanism which causes the disease being represented by a type-I hypersensibility reaction. The mechanism which determines the appearance of the corneal lesions isn't entirely cleared up, but there are however some pathogenic links which have been already deciphered. The type I hypersensibility reaction is taking place within two stages: stage I the stage of the sensitizing contact and stage II the stage of the unleashing contact. During the first stage, the Langerhans cells take over and process the allergen, exhibiting on their surface only the antigenic part. The Langerhans cells interact with the T helper native cells (Tho), cells from which there will result the predominantly differentiated Th2 subtype. The Thz cells will activate, by means of the interleukines, the B cells (which produce the IgE), the mast cells and the eosinophilic cells. During the second stage, the allergen is coming into contact with the IgE specific antibodies, which are fastened on the mast cells membrane, generating the opening of their granules. The result of this evolution is represented by the unleash of vasoactive mediators, own enzymes, chemical mediators (among which there is also the eosinophilic chemotactic factor ECFA). The latter contributes to the infiltration of the epithelial and of the subepithelial tissue with eosinophilic cells. The major basic protein (PBM), one of the proteins released from the eosinophilic cells' big granules, plays a major pathogenic role in the production of the corneal ulcer, by means of its direct cytotoxic effect and also by means of inhibiting the migration of the epithelial corneal cells. The role of the mast cells and also the role of the neutrophile cells within the framework of the pathogenesis of the ulcer is disputable, because some specific enzymes tryptase, respectively elastase--have been found within the

  15. [Corneal ulcerative lesions in type-I immediate hypersensitivity].

    PubMed

    Giuri, S

    1998-01-01

    The vernal keratoconjunctivitis (KCV) is included within the category of the hypersensitiveness diseases, the immunopathological mechanism which causes the disease being represented by a type-I hypersensibility reaction. The mechanism which determines the appearance of the corneal lesions isn't entirely cleared up, but there are however some pathogenic links which have been already deciphered. The type I hypersensibility reaction is taking place within two stages: stage I the stage of the sensitizing contact and stage II the stage of the unleashing contact. During the first stage, the Langerhans cells take over and process the allergen, exhibiting on their surface only the antigenic part. The Langerhans cells interact with the T helper native cells (Tho), cells from which there will result the predominantly differentiated Th2 subtype. The Thz cells will activate, by means of the interleukines, the B cells (which produce the IgE), the mast cells and the eosinophilic cells. During the second stage, the allergen is coming into contact with the IgE specific antibodies, which are fastened on the mast cells membrane, generating the opening of their granules. The result of this evolution is represented by the unleash of vasoactive mediators, own enzymes, chemical mediators (among which there is also the eosinophilic chemotactic factor ECFA). The latter contributes to the infiltration of the epithelial and of the subepithelial tissue with eosinophilic cells. The major basic protein (PBM), one of the proteins released from the eosinophilic cells' big granules, plays a major pathogenic role in the production of the corneal ulcer, by means of its direct cytotoxic effect and also by means of inhibiting the migration of the epithelial corneal cells. The role of the mast cells and also the role of the neutrophile cells within the framework of the pathogenesis of the ulcer is disputable, because some specific enzymes tryptase, respectively elastase--have been found within the

  16. Periaqueductal Grey EP3 Receptors Facilitate Spinal Nociception in Arthritic Secondary Hypersensitivity

    PubMed Central

    Drake, R.A.R.; Leith, J.L.; Almahasneh, F.; Martindale, J.; Wilson, A.W.; Lumb, B.

    2016-01-01

    Descending controls on spinal nociceptive processing play a pivotal role in shaping the pain experience after tissue injury. Secondary hypersensitivity develops within undamaged tissue adjacent and distant to damaged sites. Spinal neuronal pools innervating regions of secondary hypersensitivity are dominated by descending facilitation that amplifies spinal inputs from unsensitized peripheral nociceptors. Cyclooxygenase–prostaglandin (PG) E2 signaling within the ventrolateral periaqueductal gray (vlPAG) is pronociceptive in naive and acutely inflamed animals, but its contributions in more prolonged inflammation and, importantly, secondary hypersensitivity remain unknown. In naive rats, PG EP3 receptor (EP3R) antagonism in vlPAG modulated noxious withdrawal reflex (EMG) thresholds to preferential C-nociceptor, but not A-nociceptor, activation and raised thermal withdrawal thresholds in awake animals. In rats with inflammatory arthritis, secondary mechanical and thermal hypersensitivity of the hindpaw developed and was associated with spinal sensitization to A-nociceptor inputs alone. In arthritic rats, blockade of vlPAG EP3R raised EMG thresholds to C-nociceptor activation in the area of secondary hypersensitivity to a degree equivalent to that evoked by the same manipulation in naive rats. Importantly, vlPAG EP3R blockade also affected responses to A-nociceptor activation, but only in arthritic animals. We conclude that vlPAG EP3R activity exerts an equivalent facilitation on the spinal processing of C-nociceptor inputs in naive and arthritic animals, but gains in effects on spinal A-nociceptor processing from a region of secondary hypersensitivity. Therefore, the spinal sensitization to A-nociceptor inputs associated with secondary hypersensitivity is likely to be at least partly dependent on descending prostanergic facilitation from the vlPAG. SIGNIFICANCE STATEMENT After tissue damage, sensitivity to painful stimulation develops in undamaged areas (secondary

  17. The sequence of the groES and groEL genes from the mouse pneumonitis agent of Chlamydia trachomatis.

    PubMed

    Ho, Y; Zhang, Y X

    1994-04-01

    The co-transcribed structural genes, groES and groEL, of the groE stress response operon from Chlamydia trachomatis mouse pneumonitis (MoPn), were cloned and sequenced. The calculated molecular masses of the encoded heat-shock proteins (Hsp), a small Hsp (GroES) and Hsp60 (GroEL), are 11,089 and 58,367 Da, respectively. By comparison with other known chlamydial groES and groEL sequences, there is 89 and 94% nucleotide (nt) identity with C. trachomatis human strains (serovars A and L2), 77 and 82% with C. psittaci strain GPIC, and 75 and 80% with C. pneumoniae isolate AR-39. At the amino-acid level, the MoPn Hsp60 shows a 99% identity with those from C. trachomatis human strains. In a mouse model, MoPn Hsp60 could prove useful in deciphering the pathogenesis of human chlamydial diseases.

  18. Mesoporous Silica Nanoparticles with pH-Sensitive Nanovalves for Delivery of Moxifloxacin Provide Improved Treatment of Lethal Pneumonic Tularemia.

    PubMed

    Li, Zilu; Clemens, Daniel L; Lee, Bai-Yu; Dillon, Barbara Jane; Horwitz, Marcus A; Zink, Jeffrey I

    2015-11-24

    We have optimized mesoporous silica nanoparticles (MSNs) functionalized with pH-sensitive nanovalves for the delivery of the broad spectrum fluoroquinolone moxifloxacin (MXF) and demonstrated its efficacy in treating Francisella tularensis infections both in vitro and in vivo. We compared two different nanovalve systems, positive and negative charge modifications of the mesopores, and different loading conditions-varying pH, cargo concentration, and duration of loading-and identified conditions that maximize both the uptake and release capacity of MXF by MSNs. We have demonstrated in macrophage cell culture that the MSN-MXF delivery platform is highly effective in killing F. tularensis in infected macrophages, and in a mouse model of lethal pneumonic tularemia, we have shown that the drug-loaded MSNs are much more effective in killing F. tularensis than an equivalent amount of free MXF.

  19. Objective clinical and laboratory studies of immediate hypersensitivity reactions to foods in asthmatic children.

    PubMed

    May, C D

    1976-10-01

    Clinical and laboratory observations were made with 38 children afflicted with chronic severe asthma (reversible obstructive airway disease) in which hypersensitivity to food was incriminated in the histories. Symptoms were evoked in double-blind food challenges in only 11/38 children and 14/70 challenges, and were characteristic of immediate-type hypersensitivity and were chiefly gastrointestinal, even though asthma was the common presenting complaint. There were no delayed reactions. Peanut was responsible for 8 reactions, egg for 5, and cow's milk for 1. The feature that most successfully identified those having positive reactions in challenges was a significant wheal reaction in a skin test by puncture technique using a verified extract of 1:20 W/V concentration. No subject with clinically significant, symptomatic hypersensitivity to food had a negative puncture test, and puncture tests were positive in only 10/56 instances of negative reactions in food challenges. Laboratory observations included release of histamine and enzymes from leukocytes and the levels of neutrophil enzymes in serum before and after food provocation tests. While these determinations were of interest with respect to the immunochemical basis of reactions to foods, they did not prove useful for practical clinical diagnosis. The outstanding laboratory findings was the occurrence of "spontaneous" release of 25% to 100% of the histamine from leukocytes in all cases proved clinically hypersensitive by food challenges, which suggests that this may be an indicator of immediate-type hypersensitivity to food. From the findings in the study, a general approach to food hypersensitivity was developed in which the immunologic components coupled with quantitative concentration-response relationships serve to render comprehensible the distinction between asymptomatic (immunologic) hypersensitivity and symptomatic (clinical) hypersensitivity.

  20. Contribution of afferent pathways to nerve injury-induced spontaneous pain and evoked hypersensitivity.

    PubMed

    King, Tamara; Qu, Chaoling; Okun, Alec; Mercado, Ramon; Ren, Jiyang; Brion, Triza; Lai, Josephine; Porreca, Frank

    2011-09-01

    A predominant complaint in patients with neuropathic pain is spontaneous pain, often described as burning. Recent studies have demonstrated that negative reinforcement can be used to unmask spontaneous neuropathic pain, allowing for mechanistic investigations. Here, ascending pathways that might contribute to evoked and spontaneous components of an experimental neuropathic pain model were explored. Desensitization of TRPV1-positive fibers with systemic resiniferatoxin (RTX) abolished spinal nerve ligation (SNL) injury-induced thermal hypersensitivity and spontaneous pain, but had no effect on tactile hypersensitivity. Ablation of spinal NK-1 receptor-expressing neurons blocked SNL-induced thermal and tactile hypersensitivity as well as spontaneous pain. After nerve injury, upregulation of neuropeptide Y (NPY) is observed almost exclusively in large-diameter fibers, and inactivation of the brainstem target of these fibers in the nucleus gracilis prevents tactile but not thermal hypersensitivity. Blockade of NPY signaling within the nucleus gracilis failed to block SNL-induced spontaneous pain or thermal hyperalgesia while fully reversing tactile hypersensitivity. Moreover, microinjection of NPY into nucleus gracilis produced robust tactile hypersensitivity, but failed to induce conditioned place aversion. These data suggest that spontaneous neuropathic pain and thermal hyperalgesia are mediated by TRPV1-positive fibers and spinal NK-1-positive ascending projections. In contrast, the large-diameter dorsal column projection can mediate nerve injury-induced tactile hypersensitivity, but does not contribute to spontaneous pain. Because inhibition of tactile hypersensitivity can be achieved either by spinal manipulations or by inactivation of signaling within the nucleus gracilis, the enhanced paw withdrawal response evoked by tactile stimulation does not necessarily reflect allodynia.

  1. Recent applications of basophil activation tests in the diagnosis of drug hypersensitivity

    PubMed Central

    Song, Woo-Jung

    2013-01-01

    Immediate-type drug hypersensitivity is an increasingly significant clinical issue; however, the diagnosis is frequently hindered due to lack of safe and precise diagnostic tests. Flow cytometry-assisted basophil activation test is a safe in vitro diagnostic tool for assessing basophil activation upon allergen stimulation. In this review, we have summarized current literature on the diagnostic utilities, new indications, and methodological aspects of the basophil activation test for the diagnosis of drug hypersensitivity. PMID:24260732

  2. Low incidence of abacavir hypersensitivity reaction among African children initiating antiretroviral therapy.

    PubMed

    Nahirya-Ntege, Patricia; Musiime, Victor; Naidoo, Bethany; Bakeera-Kitaka, Sabrina; Nathoo, Kusum; Munderi, Paula; Mugyenyi, Peter; Kekitiinwa, Adeodata; Bwakura-Dangarembizi, Mutsa F; Crawley, Jane

    2011-06-01

    Hypersensitivity reactions are reported in approximately 5% of adults receiving abacavir, but there are few published data in children. Among 1150 African children receiving antiretroviral therapy in a randomized trial, suspected hypersensitivity reactions to abacavir were rare (0.3%; 95% CI, 0.01-0.9). Patients were managed successfully through the provision of clear guidelines and education of clinical staff, children, and their caregivers.

  3. The management of blood phobia and a hypersensitive gag reflex by hypnotherapy: a case report.

    PubMed

    Noble, Suzanne

    2002-03-01

    Coping with a hypersensitive gag reflex can be a cause for concern for both the patient and the operator. This report describes a case of blood phobia directed solely towards the oral cavity, linked with the inability to tolerate dentures due to a hypersensitive gag reflex. Management by hypnotherapy using a systematic desensitization technique allowed for extraction of teeth and permanent elimination of the gagging problem.

  4. Yersinia pestis Endowed with Increased Cytotoxicity Is Avirulent in a Bubonic Plague Model and Induces Rapid Protection against Pneumonic Plague

    PubMed Central

    Zauberman, Ayelet; Tidhar, Avital; Levy, Yinon; Bar-Haim, Erez; Halperin, Gideon; Flashner, Yehuda; Cohen, Sara; Shafferman, Avigdor; Mamroud, Emanuelle

    2009-01-01

    An important virulence strategy evolved by bacterial pathogens to overcome host defenses is the modulation of host cell death. Previous observations have indicated that Yersinia pestis, the causative agent of plague disease, exhibits restricted capacity to induce cell death in macrophages due to ineffective translocation of the type III secretion effector YopJ, as opposed to the readily translocated YopP, the YopJ homologue of the enteropathogen Yersinia enterocolitica O∶8. This led us to suggest that reduced cytotoxic potency may allow pathogen propagation within a shielded niche, leading to increased virulence. To test the relationship between cytotoxic potential and virulence, we replaced Y. pestis YopJ with YopP. The YopP-expressing Y. pestis strain exhibited high cytotoxic activity against macrophages in vitro. Following subcutaneous infection, this strain had reduced ability to colonize internal organs, was unable to induce septicemia and exhibited at least a 107-fold reduction in virulence. Yet, upon intravenous or intranasal infection, it was still as virulent as the wild-type strain. The subcutaneous administration of the cytotoxic Y. pestis strain appears to activate a rapid and potent systemic, CTL-independent, immunoprotective response, allowing the organism to overcome simultaneous coinfection with 10,000 LD50 of virulent Y. pestis. Moreover, three days after subcutaneous administration of this strain, animals were also protected against septicemic or primary pneumonic plague. Our findings indicate that an inverse relationship exists between the cytotoxic potential of Y. pestis and its virulence following subcutaneous infection. This appears to be associated with the ability of the engineered cytotoxic Y. pestis strain to induce very rapid, effective and long-lasting protection against bubonic and pneumonic plague. These observations have novel implications for the development of vaccines/therapies against Y. pestis and shed new light on the

  5. Food Hypersensitivity in Patients Over 14 Years of Age Suffering from Atopic Dermatitis

    PubMed Central

    Čelakovská, Jarmila; Ettler, K; Ettlerová, K; Vaněčková, J

    2014-01-01

    Background: Patients suffering from atopic dermatitis often describe food hypersensitivity. Rising prevalence of food hypersensitivity and severe allergic reactions to foods have been reported, but the data are scarce. Aims and Objectives: Evaluation of food hypersensitivity reactions in patients suffering from atopic dermatitis. Materials and Methods: The dermatological examination was performed in patients of age 14 years and above and the detailed history was taken concerning the food hypersensitivity. Results: A total of 228 patients were examined-72 men, 156 women, average age 26.2 (SD 9.5) years. The food hypersensitivity reactions were recorded in 196 patients from 228 (86%), no reactions were recorded in 32 patients (24%). Foods with the most often recorded reactions are: Nuts (in 35% of patients), tomatoes (in 20%), and kiwi (in 17, 5%), apples and spices (in 16%), tangerines and oranges (in 15%), capsicum (in 13%), fishes (in 12%), celery (in 9%), and chocolate (in 7%). Conclusion: Food hypersensitivity reactions are recorded in 86% of patients suffering from atopic dermatitis. Nuts, tomatoes, and pollen–associated foods play a role in the majority of patients suffering from atopic dermatitis. PMID:24891679

  6. Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity

    PubMed Central

    La, Jun-ho; Schwartz, Erica S.; Tanaka, Takahiro; McMurray, Timothy P.; Gebhart, G. F.

    2012-01-01

    Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15–60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the distal colorectum with the pelvic nerve attached was removed for single-fiber electrophysiological recordings. Colorectal afferent endings were located by electrical stimulation and characterized as mechanosensitive or not by blunt probing, mucosal stroking, and circumferential stretch. Intracolonic zymosan produced persistent colorectal hypersensitivity (>24 days) associated with brief colorectal inflammation. Pelvic nerve muscular-mucosal but not muscular mechanosensitive afferents recorded from mice with colorectal hypersensitivity exhibited persistent sensitization. In addition, the proportion of MIAs (relative to control) was significantly reduced from 27% to 13%, whereas the proportion of serosal afferents was significantly increased from 34% to 53%, suggesting that MIAs acquired mechanosensitivity. PGP9.5 immunostaining revealed no significant loss of colorectal nerve fiber density, suggesting that the reduction in MIAs is not due to peripheral fiber loss after intracolonic zymosan. These results indicate that colorectal MIAs and sensitized muscular-mucosal afferents that respond to stretch contribute significantly to the afferent input that sustains hypersensitivity to CRD, suggesting that targeted management of colorectal afferent input could significantly reduce patients' complaints of pain and hypersensitivity. PMID:22268098

  7. Session 1: Allergic disease: The challenges of managing food hypersensitivity.

    PubMed

    Venter, Carina; Meyer, Rosan

    2010-02-01

    Food hypersensitivity (FHS) is the umbrella term used for food allergies that involve the immune system and food intolerances that do not involve the immune system. FHS has a huge impact on quality of life and any dietary advice given should aim to minimise this effect. Despite many advances made in diagnosing and managing patients with FHS, the cornerstone of management still remains avoidance of the relevant food. However, a commonly-presenting dilemma in clinical practice is deciding to what extent the food(s) should be avoided. The level of avoidance required is currently based on the type of FHS the patient has, characteristics of the particular food protein and the natural history of the particular FHS. In addition to management of other FHS, management of cow's milk allergy requires the healthcare professional to choose the appropriate formula. Information required by the patient also includes understanding food labels and issues surrounding cross-contamination. In order to ensure that the diet is nutritionally sound, advice should be given about suitable food choices and following a healthy balanced diet, whilst taking into account the dietary restrictions. Practical issues that need to be addressed include going on holiday, travelling and eating away from home. The dietitian plays a crucial role in this process. At present, there are no standardised documents or protocols for the management of FHS and practices differ within and between countries. If adrenaline auto-injectors are prescribed, correct administration should be demonstrated and reviewed on an ongoing basis. PMID:20003636

  8. Exploring Some Aspects Associated with Dentine Hypersensitivity in Children

    PubMed Central

    Shitsuka, Caleb; Mendes, Fausto Medeiros; Corrêa, Maria Salete Nahás Pires; Leite, Mariana Ferreira

    2015-01-01

    Background. The etiology of dentine hypersensitivity (DH) is still inconclusive and there are few studies concerning it in children. Aim. To evaluate clinical, dietary, and salivary variables in children with DH complaints. Design. Forty-eight children were asked about DH. Data regarding dietary habits were collected from the children's parents and an examination was performed to determine dental erosion. Dental biofilm was estimated by oral hygiene status, according to Greene and Vermillion's Simplified Oral Hygiene Index (OHI-S). Whole saliva was collected under mechanical stimulation and evaluated salivary flow rate, initial pH, buffer capacity, and calcium and phosphate concentrations. The temperature of soft drinks, drinking method, sense of bitter taste, and other variables were also determined. Possible factors associated with DH were analyzed by univariate and multiple Poisson regression analyses. The prevalence ratio (PR) values and 95% confidence intervals (95% CI) were calculated. Results. DH was associated with the presence of dental erosion (PR; 95% CI = 2.23; 1.05 to 4.71) and salivary flow rate (2.49; 1.05 to 5.91). When the presence of erosion was not included, other variables were retained as follows: bitter taste (2.36; 1.38 to 4.03), OHI-S (0.47; 0.23 to 0.97). Conclusion. DH in children is associated with factors related to dental erosion. PMID:25879070

  9. Segmental hypersensitivity and spinothalamic function in spinal cord injury pain.

    PubMed

    Finnerup, Nanna B; Sørensen, Leif; Biering-Sørensen, Fin; Johannesen, Inger L; Jensen, Troels S

    2007-09-01

    The mechanisms underlying central pain following spinal cord injury (SCI) are unsettled. The purpose of the present study was to examine differences in spinothalamic tract function below injury level and evoked pain in incomplete SCI patients with neuropathic pain below injury level (central pain) versus those without such pain. A clinical examination, quantitative sensory testing and magnetic resonance imaging (MRI) were performed in 10 SCI patients with below-level pain and in 11 SCI patients without neuropathic pain. Patients with and without pain had similar reductions of mechanical and thermal detection thresholds below injury level. SCI patients with central pain had sensory hypersensitivity in dermatomes corresponding to the lesion level more frequently than SCI patients without pain, but this may in part be explained by the exclusion of at-level spontaneous pain in the pain-free group. The rostral-caudal extent of the lesion measured by MRI did not differ between the two patient groups, and there were no statistically significant differences in any of the predefined areas of interest on the axial plane images. This study suggests that neuronal hyperexcitability plays a key role in central SCI pain and furthermore - in contrast to previous findings - that loss of spinothalamic functions does not appear to be a predictor for central neuropathic pain in spinal cord injury.

  10. Re-visiting Hypersensitivity Reactions to Taxanes: A Comprehensive Review.

    PubMed

    Picard, Matthieu; Castells, Mariana C

    2015-10-01

    Taxanes (a class of chemotherapeutic agents) are an important cause of hypersensitivity reactions (HSRs) in cancer patients. During the last decade, the development of rapid drug desensitization has been key to allow patients with HSRs to taxanes to be safely re-treated although the mechanisms of these HSRs are not fully understood. Earlier studies suggested that solvents, such as Cremophor EL used to solubilize paclitaxel, were responsible for HSRs through complement activation, but recent findings have raised the possibility that some of these HSRs are IgE-mediated. Taxane skin testing, which identifies patients with an IgE-mediated sensitivity, appears as a promising diagnostic and risk stratification tool in the management of patients with HSRs to taxanes. The management of patients following a HSR involves risk stratification and re-exposure could be performed either through rapid drug desensitization or graded challenge based on the severity of the initial HSR and the skin test result. Rapid drug desensitization has been shown to be an effective and safe method to re-introduce taxanes in hundreds of patients, including those with life-threatening HSRs. Patients with non-severe delayed skin HSRs may benefit from rapid drug desensitization since they may be at increased risk for an immediate HSR upon re-exposure. This review focuses on the clinical presentation, diagnosis, and novel mechanisms of immediate HSRs to taxanes. A new management strategy for HSRs to taxanes based on skin testing and rapid drug desensitization is proposed.

  11. Clinical Features of Oxaliplatin Induced Hypersensitivity Reactions and Therapeutic Approaches.

    PubMed

    Bano, Nusrat; Najam, Rahila; Qazi, Faaiza; Mateen, Ahmed

    2016-01-01

    Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan. PMID:27221832

  12. Clinical Features of Oxaliplatin Induced Hypersensitivity Reactions and Therapeutic Approaches.

    PubMed

    Bano, Nusrat; Najam, Rahila; Qazi, Faaiza; Mateen, Ahmed

    2016-01-01

    Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan.

  13. Evaluation of the hypersensitivity potential of alternative butter flavorings

    PubMed Central

    Anderson, Stacey E.; Franko, Jennifer; Wells, J.R.; Lukomska, Ewa; Meade, B. Jean

    2015-01-01

    Concern has been raised over the association of diacetyl with lung disease clinically resembling bronchiolitis obliterans in food manufacturing workers. This has resulted in the need for identification of alternative chemicals to be used in the manufacturing process. Structurally similar chemicals, 2,3-pentanedione, 2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione, used as constituents of synthetic flavoring agents have been suggested as potential alternatives for diacetyl, however, immunotoxicity data on these chemicals are limited. The present study evaluated the dermal irritation and sensitization potential of diacetyl alternatives using a murine model. None of the chemicals were identified as dermal irritants when tested at concentrations up to 50%. Similar to diacetyl (EC3 = 17.9%), concentration-dependent increases in lymphocyte proliferation were observed following exposure to all four chemicals, with calculated EC3 values of 15.4% (2,3-pentanedione), 18.2% (2,3-hexanedione), 15.5% (3,4-hexanedione) and 14.1% (2,3-heptanedione). No biologically significant elevations in local or total serum IgE were identified after exposure to 25–50% concentrations of these chemicals. These results demonstrate the potential for development of hypersensitivity responses to these proposed alternative butter flavorings and raise concern about the use of structurally similar replacement chemicals. Additionally, a contaminant with strong sensitization potential was found in varying concentrations in diacetyl obtained from different producers. PMID:24007741

  14. Treatment of Dentine Hypersensitivity by Diode Laser: A Clinical Study

    PubMed Central

    Umberto, Romeo; Claudia, Russo; Gaspare, Palaia; Gianluca, Tenore; Alessandro, Del Vecchio

    2012-01-01

    Introduction. Dentine hypersensitivity (DH) is characterized by pain after stimuli that usually provoke no symptoms. This study compared the effectiveness of GaAlAs diode laser alone and with topical sodium fluoride gel (NaF). Materials and Methods. The study was conducted on 10 patients (8 F/2 M, age 25–60) and 115 teeth with DH assessed by air and tactile stimuli measured by Numeric Rating Scale (NRS). Teeth were randomly divided into G1 (34 teeth) treated by 1.25% NaF; G2 (33 teeth) lased at 0.5 W PW (T on 100 m and T off 100 ms), fluence 62.2 J/cm2 in defocused mode with a 320 μ fiber. Each tooth received three 1′ applications; G3 (48 teeth) received NaF gel plus laser at same G2 parameters. NRS was checked at each control. Results. Significant pain reduction was showed. The NRS reduction percentages were calculated, and there was a concrete decrease of DH above all in G3 than G2 and G1. Conclusion. Diode laser is a useful device for DH treatment if used alone and mainly if used with NaF gel. PMID:22792109

  15. Equine insect bite hypersensitivity: what do we know?

    PubMed

    Schaffartzik, A; Hamza, E; Janda, J; Crameri, R; Marti, E; Rhyner, C

    2012-06-30

    Insect bite hypersensitivity (IBH) is an allergic dermatitis of the horse caused by bites of insects of the genus Culicoides and is currently the best characterized allergic disease of horses. This article reviews knowledge of the immunopathogenesis of IBH, with a particular focus on the causative allergens. Whereas so far hardly any research has been done on the role of antigen presenting cells in the pathogenesis of IBH, recent studies suggest that IBH is characterized by an imbalance between a T helper 2 (Th2) and regulatory T cell (T(reg)) immune response, as shown both locally in the skin and with stimulated peripheral blood mononuclear cells. Various studies have shown IBH to be associated with IgE-mediated reactions against salivary antigens from Culicoides spp. However, until recently, the causative allergens had not been characterized at the molecular level. A major advance has now been made, as 11 Culicoides salivary gland proteins have been identified as relevant allergens for IBH. Currently, there is no satisfactory treatment of IBH. Characterization of the main allergens for IBH and understanding what mechanisms induce a healthy or allergic immune response towards these allergens may help to develop new treatment strategies, such as immunotherapy.

  16. Diagnosing the tight building syndrome or diagnosing chemical hypersensitivity

    SciTech Connect

    Rogers, S.A. )

    1989-01-01

    The abrupt exposure to urea foam formaldehyde insulation served as an alert to its spectrum of symptoms, including attacks of headache, flushing, laryngitis, dizziness, nausea, extreme weakness or exhaustion, arthralgia, an inability to concentrate, unwarranted depression, arrhythmia, or muscle spasms, and baffled physicians from many specialties. Later it was learned that toluene, xylene, benzene, natural gas, trichloroethylene, and many other chemicals were also capable of triggering chemical hypersensitivity. Other names for this condition include Environmentally Induced Illness (EI), the Tight Building Syndrome (TBS), the Sick Building Syndrome, and Building-Related Illness. The very symptoms patients complain of can be provoked within minutes and then subsequently alleviated with an intradermal injection of the appropriate strength of the triggering chemical. This technique aids in convincing the patient of the EI or TBS triggers so that the patient can begin to relate symptoms to environmental exposures and initiate measure to bring the disease under control. The key to safer buildings is increased ventilation, increased filtration of air, and decreased use of off-gassing synthetic materials.

  17. Evaluation of the hypersensitivity potential of alternative butter flavorings.

    PubMed

    Anderson, Stacey E; Franko, Jennifer; Wells, J R; Lukomska, Ewa; Meade, B Jean

    2013-12-01

    Concern has been raised over the association of diacetyl with lung disease clinically resembling bronchiolitis obliterans in food manufacturing workers. This has resulted in the need for identification of alternative chemicals to be used in the manufacturing process. Structurally similar chemicals, 2,3-pentanedione, 2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione, used as constituents of synthetic flavoring agents have been suggested as potential alternatives for diacetyl, however, immunotoxicity data on these chemicals are limited. The present study evaluated the dermal irritation and sensitization potential of diacetyl alternatives using a murine model. None of the chemicals were identified as dermal irritants when tested at concentrations up to 50%. Similar to diacetyl (EC3=17.9%), concentration-dependent increases in lymphocyte proliferation were observed following exposure to all four chemicals, with calculated EC3 values of 15.4% (2,3-pentanedione), 18.2% (2,3-hexanedione), 15.5% (3,4-hexanedione) and 14.1% (2,3-heptanedione). No biologically significant elevations in local or total serum IgE were identified after exposure to 25-50% concentrations of these chemicals. These results demonstrate the potential for development of hypersensitivity responses to these proposed alternative butter flavorings and raise concern about the use of structurally similar replacement chemicals. Additionally, a contaminant with strong sensitization potential was found in varying concentrations in diacetyl obtained from different producers.

  18. Nedocromil sodium in two models of conjunctival immediate hypersensitivity.

    PubMed

    McGrath, L E; Doherty, M J; Easty, D L; Norris, A

    2000-01-01

    The effects of intravenous administration of nedocromil sodium were investigated in active and passive models of conjunctival immediate hypersensitivity in rats. In the active sensitization model, animals were immunized with ovalbumin 21 days prior to ocular instillation of a solution containing ovalbumin. Nedocromil sodium administered prior to antigen challenge significantly inhibited emergence of conjunctival edema and erythema (P < .05) and reduced mast cell degranulation (P < .02). In the passive-sensitization model, the conjunctiva in one eye was injected with ovalbumin antiserum 48 hours prior to intravenous administration of ovalbumin. Nedocromil sodium administered prior to antigen challenge significantly and dose-dependently reduced appearance of the signs of conjunctivitis (P < .01) as well as vascular leakage (P < .05). These data indicate that intravenous nedocromil sodium is effective in animal models of allergic conjunctivitis and may have potential for wider therapeutic application. These data are also consistent with results of clinical studies in which nedocromil sodium relieved symptoms of allergic conjunctivitis and further support a role for nedocromil sodium in the prevention of allergic conjunctivitis.

  19. Osteopontin Is Involved in the Initiation of Cutaneous Contact Hypersensitivity by Inducing Langerhans and Dendritic Cell Migration to Lymph Nodes

    PubMed Central

    Weiss, J.M.; Renkl, A.C.; Maier, C.S.; Kimmig, M.; Liaw, L.; Ahrens, T.; Kon, S.; Maeda, M.; Hotta, H.; Uede, T.; Simon, J.C.

    2001-01-01

    Osteopontin (OPN) is a chemotactic protein that attracts immune cells, to inflammatory sites. The sensitization phase of allergic cutaneous contact hypersensitivity (CHS) requires the migration of Langerhans cells/dendritic cells (LCs/DCs) from skin to draining lymph nodes. Characterizing OPN function for LC/DC migration we found upregulated OPN expression in hapten sensitized skin and draining lymph nodes. OPN induces chemotactic LC/DC migration, initiates their emigration from the epidermis, and attracts LCs/DCs to draining lymph nodes by interacting with CD44 and αv integrin. Furthermore, OPN-deficient mice have a significantly reduced CHS response that correlates with an impaired ability of OPN-deficient mice to attract LCs/DCs to draining lymph nodes. In conclusion, OPN is an important factor in the initiation of CHS by guiding LCs/DCs from skin into lymphatic organs. PMID:11696588

  20. Biomaterial Hypersensitivity: Is It Real? Supportive Evidence and Approach Considerations for Metal Allergic Patients following Total Knee Arthroplasty

    PubMed Central

    Mihalko, William M.; Grupp, Thomas M.; Manning, Blaine T.; Dennis, Douglas A.; Goodman, Stuart B.; Saleh, Khaled J.

    2015-01-01

    The prospect of biomaterial hypersensitivity developing in response to joint implant materials was first presented more than 30 years ago. Many studies have established probable causation between first-generation metal-on-metal hip implants and hypersensitivity reactions. In a limited patient population, implant failure may ultimately be related to metal hypersensitivity. The examination of hypersensitivity reactions in current-generation metal-on-metal knee implants is comparatively limited. The purpose of this study is to summarize all available literature regarding biomaterial hypersensitivity after total knee arthroplasty, elucidate overall trends about this topic in the current literature, and provide a foundation for clinical approach considerations when biomaterial hypersensitivity is suspected. PMID:25883940

  1. Biomaterial hypersensitivity: is it real? Supportive evidence and approach considerations for metal allergic patients following total knee arthroplasty.

    PubMed

    Mitchelson, Andrew J; Wilson, Craig J; Mihalko, William M; Grupp, Thomas M; Manning, Blaine T; Dennis, Douglas A; Goodman, Stuart B; Tzeng, Tony H; Vasdev, Sonia; Saleh, Khaled J

    2015-01-01

    The prospect of biomaterial hypersensitivity developing in response to joint implant materials was first presented more than 30 years ago. Many studies have established probable causation between first-generation metal-on-metal hip implants and hypersensitivity reactions. In a limited patient population, implant failure may ultimately be related to metal hypersensitivity. The examination of hypersensitivity reactions in current-generation metal-on-metal knee implants is comparatively limited. The purpose of this study is to summarize all available literature regarding biomaterial hypersensitivity after total knee arthroplasty, elucidate overall trends about this topic in the current literature, and provide a foundation for clinical approach considerations when biomaterial hypersensitivity is suspected. PMID:25883940

  2. Pharmacological attenuation of chronic alcoholic pancreatitis induced hypersensitivity in rats

    PubMed Central

    McIlwrath, Sabrina L; Westlund, Karin N

    2015-01-01

    AIM: To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices. METHODS: Experimental rats were fed a modified Lieber-DeCarli alcohol (6%) and high-fat (65%) diet (AHF) for 10 wk while control animals received a regular rodent chow diet. Weekly behavioral tests determined mechanical and heat sensitivity. In week 10 a fasting glucose tolerance test was performed, measuring blood glucose levels before and after a 2 g/kg bodyweight intraperitoneal (i.p.) injection of glucose. Post mortem histological analysis was performed by staining pancreas and liver tissue sections with hematoxylin and eosin. Pancreas sections were also stained with Sirius red and fast green to quantify collagen content. Insulin-expressing cells were identified immunohistochemically in separate sections. Tissue staining density was quantified using Image J software. After mechanical and heat sensitivity became stable (weeks 6-10) in the AHF-fed animals, three different drugs were tested for their efficacy in attenuating pancreatitis associated hypersensitivity: a Group II metabotropic glutamate receptor specific agonist (2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate (APDC, 3 mg/kg, ip; Tocris, Bristol, United Kingdom), nociceptin (20, 60, 200 nmol/kg, ip; Tocris), and morphine sulfate (3 mg/kg, μ-opioid receptor agonist; Baxter Healthcare, Deerfield, IL, United States). RESULTS: Histological analysis of pancreas and liver determined that unlike control rats, AHF fed animals had pancreatic fibrosis, acinar and beta cell atrophy, with steatosis in both organs. Fat vacuolization was significantly increased in AHF fed rats (6.4% ± 1.1% in controls vs 23.8% ± 4.2%, P < 0.05). Rats fed the AHF diet had reduced fasting glucose tolerance in week 10 when peak blood glucose levels reached significantly higher concentrations than controls (127.4 ± 9.2 mg/dL in controls vs 161.0 ± 8.6 mg/dL, P < 0.05). This concurred with a 3.5 fold higher

  3. Evaluation of the Effect of Low Level Laser Therapy Toothbrush in Treatment of Dentin Hypersensitivity

    PubMed Central

    Yaghini, Jaber; Mogharehabed, Ahmad; Safavi, Nassimeh; Mohamadi, Mehrnush; Ashtiju, Fahime

    2015-01-01

    Introduction: Dentin hypersensitivity is one of the most common complications that affect patients after periodontal therapy. Recently low level laser therapy has been introduced as a new treatment modality and has produced beneficial results. The purpose of this study is to evaluate the effect of low level laser therapy toothbrushes in reduction of dentin hypersensitivity. Methods: In this pilot interventional controlled clinical trial, 40 patients suffering from dentin hypersensitivity were selected using simple randomization. Half of the patients were given laser toothbrushes and the other half was given non-laser sensodyne toothbrushes. Primary dentin hypersensitivity was recorded by visual analogue scale (VAS) score and ice spray. Then dentin hypersensitivity was measured right after the treatment as well az in the intervals of 1 month and 2 months after initiation of the study. Data were compared using Statistical Package for the Social Sciences (SPSS) software and Analysis of variance (ANOVA) paired T test. Results: The results of this study showed that there was a significant difference in each of the two kinds of tooth brushes separately for all time intervals (P < 0.001). Also the effect of the type of toothbrush was investigated using before treatment VAS with covariance analyses. P values for immediately, 1 month and 2 months after treatment were calculated to be 0.078, 0.02, 0.01 respectfully. Also the effect of the toothbrush type was significant in the manner that laser toothbrushes reduce dentin hypersensitivity more than ordinary toothbrushes (P< 0.05). Conclusion: Both sensodyne and laser tooth brushes improve dentin hypersensitivity, although the laser toothbrush led to better results in short. PMID:25987974

  4. A Polyamine-Deficient Diet Prevents Oxaliplatin-Induced Acute Cold and Mechanical Hypersensitivity in Rats

    PubMed Central

    Ferrier, Jérémy; Bayet-Robert, Mathilde; Pereira, Bruno; Daulhac, Laurence; Eschalier, Alain; Pezet, Denis; Moulinoux, Jacques-Philippe; Balayssac, David

    2013-01-01

    Background Oxaliplatin is an anticancer drug used for the treatment of advanced colorectal cancer, but it can also cause painful peripheral neuropathies. The pathophysiology of these neuropathies has not been yet fully elucidated, but may involve spinal N-methyl-D-aspartate (NMDA) receptors, particularly the NR2B subunit. As polyamines are positive modulators of NMDA-NR2B receptors and mainly originate from dietary intake, the modulation of polyamines intake could represent an interesting way to prevent/modulate neuropathic pain symptoms by opposing glutamate neurotransmission. Methods The effect of a polyamine deficient diet was investigated in an animal model of oxaliplatin-induced acute pain hypersensitivity using behavioral tests (mechanical and cold hypersensitivity). The involvement of spinal glutamate neurotransmission was monitored by using a proton nuclear magnetic resonance spectroscopy based metabolomic approach and by assessing the expression and phosphorylation of the NR2B subunit of the NMDA receptor. Results A 7-day polyamine deficient diet totally prevented oxaliplatin-induced acute cold hypersensitivity and mechanical allodynia. Oxaliplatin-induced pain hypersensitivity was not associated with an increase in NR2B subunit expression or phosphorylation, but with an increase of glutamate level in the spinal dorsal horn which was completely prevented by a polyamine deficient diet. As a validation that the oxaliplatin-induced hypersensitivity could be due to an increased activity of the spinal glutamate system, an intrathecal administration of the specific NR2B antagonist, ifenprodil, totally reversed oxaliplatin-induced mechanical and cold hypersensitivity. Conclusion A polyamine deficient diet could represent a promising and valuable nutritional therapy to prevent oxaliplatin-induced acute pain hypersensitivity. PMID:24204988

  5. A novel bioactive glass-ceramic for treating dentin hypersensitivity.

    PubMed

    Tirapelli, Camila; Panzeri, Heitor; Soares, Rodrigo Gongalves; Peitl, Oscar; Zanotto, Edgar Dutra

    2010-01-01

    Dentin hypersensitivity (DH) is a painful response to stimulus applied to the open dentinal tubules of a vital tooth. It's a common oral condition, however, without an ideal treatment available yet. This work evaluated in vitro the effect of micron-sized particles from a novel bioactive glass-ceramic (Biosilicate) in occluding open dentinal tubules. A dentin disc model was employed to observe comparatively, using scanning electron microscopy (SEM), dentinal tubule occlusion by different products and deposition of hydroxyl carbonate apatite (HCA) on dentin surface by Biosilicate, after a single application: G1 - Dentifrice with potassium nitrate and fluoride; G2 - Two-step calcium phosphate precipitation treatment; G3 - Water-free gel containing Biosilicate particles (1%); G4 - Biosilicate particles mixed with distilled water in a 1:10 ratio; all of them after 1, 12 and 24 hours of immersion in artificial saliva. Fourier transform infrared spectroscopy (FTIR) was performed to detect HCA formation on dentin discs filled with Biosilicate after 2 minutes, 30 minutes and 12 hours of immersion in artificial saliva. SEM showed a layer of HCA formed on dentin surface after 24 hours by G4. G1, G2 and G3 promoted not total occlusion of open dentinal tubules after 24 hours. FTIR showed HCA precipitation on the dentin surface induced by Biosilicate after 30 minutes. The micron-sized particles from the bioactive glass-ceramic thus were able to induce HCA deposition in open dentinal tubules in vitro. This finding suggests that Biosilicate may provide a new option for treating DH. PMID:21180956

  6. The microwave syndrome or electro-hypersensitivity: historical background.

    PubMed

    Carpenter, David O

    2015-01-01

    Microwave generating equipment first became common during World War 2 with the development of radar. Soviet bloc countries reported that individuals exposed to microwaves frequently developed headaches, fatigue, loss of appetite, sleepiness, difficulty in concentration, poor memory, emotional instability, and labile cardiovascular function, and established stringent exposure standards. For a variety of reasons these reports were discounted in Western countries, where the prevailing belief was that there could be no adverse health effects of electromagnetic fields (EMFs) that were not mediated by tissue heating. The reported Soviet effects were at lower intensities than those that cause heating. However, there were several accidental exposures of radar operators in Western countries that resulted in persistent symptoms similar to those described above. The Soviets irradiated the US Embassy in Moscow with microwaves during the period 1953-1975, and while no convincing evidence of elevated cancer rates was reported, there were reports of "microwave illness". Officials passed these complaints off as being due to anxiety, not effects of the microwave exposure. There is increasing evidence that the "microwave syndrome" or "electro-hypersensitivity" (EHS) is a real disease that is caused by exposure to EMFs, especially those in the microwave range. The reported incidence of the syndrome is increasing along with increasing exposure to EMFs from electricity, WiFi, mobile phones and towers, smart meters and many other wireless devices. Why some individuals are more sensitive is unclear. While most individuals who report having EHS do not have a specific history of an acute exposure, excessive exposure to EMFs, even for a brief period of time, can induce the syndrome.

  7. [In vitro immunologic diagnosis of hypersensitivity to vegetables].

    PubMed

    Carrillo Díaz, T; Cuevas Agustín, M; Luz Díez Gómez, M; Losada Cosme, E; Moneo Goiri, I

    1986-01-01

    Acute reaction to food allergens is a fairly common problem that is often seen in the allergist's office, its incidence being specially high in childhood. Milk and eggs are the most common sensitizing foods, but usually the type of food allergens responsible for these reactions varies according to food habits in different countries. Legumes occupy an important role in the Spanish diet, being responsible for a large number of allergic reactions. It has been shown that legumes occupy the fourth place in importance among the food allergens, inducing hypersensitivity reactions in Spanish children. This article describes five patients with clinical features suggestive of being mediated by IgE antibodies specific for different legumes. In all the cases, disorders appeared immediately after the ingestion or even the inhalation of vapours from cooked legumes (lentil, bean or chick-pea). Clinical features consisted of: urticaria, angioedema, abdominal symptoms and rhinoconjunctivitis and/or asthma. The five patients required hospital emergency care on several occasions. Two patients suffered also from seasonal pollinosis with rhinoconjunctivitis and asthma. All the patients complained of these type of disorders with any legume, but lentil was found to induce the most severe reactions and it was therefore selected for this study. The presence of specific IgE antibodies was demonstrated in vivo in all the patients by means of skin prick-test. It was performed using a lentil extract prepared in our laboratory. Negative controls were also included. A reverse enzymeimmunoassay (REIA) revealed the presence of specific IgE antibodies in the sera of the five subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. The microwave syndrome or electro-hypersensitivity: historical background.

    PubMed

    Carpenter, David O

    2015-01-01

    Microwave generating equipment first became common during World War 2 with the development of radar. Soviet bloc countries reported that individuals exposed to microwaves frequently developed headaches, fatigue, loss of appetite, sleepiness, difficulty in concentration, poor memory, emotional instability, and labile cardiovascular function, and established stringent exposure standards. For a variety of reasons these reports were discounted in Western countries, where the prevailing belief was that there could be no adverse health effects of electromagnetic fields (EMFs) that were not mediated by tissue heating. The reported Soviet effects were at lower intensities than those that cause heating. However, there were several accidental exposures of radar operators in Western countries that resulted in persistent symptoms similar to those described above. The Soviets irradiated the US Embassy in Moscow with microwaves during the period 1953-1975, and while no convincing evidence of elevated cancer rates was reported, there were reports of "microwave illness". Officials passed these complaints off as being due to anxiety, not effects of the microwave exposure. There is increasing evidence that the "microwave syndrome" or "electro-hypersensitivity" (EHS) is a real disease that is caused by exposure to EMFs, especially those in the microwave range. The reported incidence of the syndrome is increasing along with increasing exposure to EMFs from electricity, WiFi, mobile phones and towers, smart meters and many other wireless devices. Why some individuals are more sensitive is unclear. While most individuals who report having EHS do not have a specific history of an acute exposure, excessive exposure to EMFs, even for a brief period of time, can induce the syndrome. PMID:26556835

  9. Contact Hypersensitivity to Oxazolone Provokes Vulvar Mechanical Hyperalgesia in Mice

    PubMed Central

    Martinov, Tijana; Glenn-Finer, Rose; Burley, Sarah; Tonc, Elena; Balsells, Evelyn; Ashbaugh, Alyssa; Swanson, Linnea; Daughters, Randy S.; Chatterjea, Devavani

    2013-01-01

    The interplay among pain, allergy and dysregulated inflammation promises to yield significant conceptual advances in immunology and chronic pain. Hapten-mediated contact hypersensitivity reactions are used to model skin allergies in rodents but have not been utilized to study associated changes in pain perception in the affected skin. Here we characterized changes in mechanical hyperalgesia in oxazolone-sensitized female mice challenged with single and repeated labiar skin exposure to oxazolone. Female mice were sensitized with topical oxazolone on their flanks and challenged 1-3 times on the labia. We then measured mechanical sensitivity of the vulvar region with an electronic pressure meter and evaluated expression of inflammatory genes, leukocyte influx and levels of innervation in the labiar tissue. Oxazolone-sensitized mice developed vulvar mechanical hyperalgesia after a single labiar oxazolone challenge. Hyperalgesia lasted up to 24 hours along with local influx of neutrophils, upregulation of inflammatory cytokine gene expression, and increased density of cutaneous labiar nerve fibers. Three daily oxazolone challenges produced vulvar mechanical hyperalgesic responses and increases in nerve density that were detectable up to 5 days post-challenge even after overt inflammation resolved. This persistent vulvar hyperalgesia is resonant with vulvodynia, an understudied chronic pain condition that is remarkably prevalent in 18-60 year-old women. An elevated risk for vulvodynia has been associated with a history of environmental allergies. Our pre-clinical model can be readily adapted to regimens of chronic exposures and long-term assessment of vulvar pain with and without concurrent inflammation to improve our understanding of mechanisms underlying subsets of vulvodynia and to develop new therapeutics for this condition. PMID:24205293

  10. The role for decorin in delayed-type hypersensitivity

    PubMed Central

    Seidler, Daniela G.; Mohamed, Negia A.; Bocian, Carla; Stadtmann, Anika; Hermann, Sven; Schäfers, Klaus; Schäfers, Michael; Iozzo, Renato V.; Zarbock, Alexander; Götte, Martin

    2016-01-01

    Decorin, a small leucine-rich proteoglycan, regulates extracellular matrix organization, growth factor-mediated signaling and cell growth. As decorin may directly modulate immune responses, we investigated its role in a mouse model of contact allergy (oxazolone-mediated delayed-type hypersensitivity, DTH) in decorin-deficient (Dcn−/−) and wild-type mice. Dcn−/− mice showed a reduced ear swelling 24 hours after oxazolone treatment with a concurrent attenuation of leukocyte infiltration. These findings were corroborated by reduced glucose metabolism as determined by 18FDG uptake in positron emission tomography scans. Unexpectedly, polymorphonuclear leukocyte numbers in Dcn−/− blood vessels were significantly increased, accompanied by large numbers of flattened leukocytes adherent to the endothelium. Intravital microscopy, flow chamber and static adhesion assays confirmed increased adhesion and reduced transmigration of Dcn−/− leukocytes. Circulating blood neutrophil numbers were significantly increased in Dcn−/− mice 24 hours after DTH elicitation, but only moderately increased in wild-type mice. Expression of the pro-inflammatory cytokine TNF-α was reduced, while syndecan-1 and ICAM-1 were overexpressed in inflamed ears of Dcn−/− mice, indicating that these adhesion molecules could be responsible for increased leukocyte adhesion. Decorin treatment of endothelial cells increased tyrosine phosphorylation and reduced syndecan-1 expression. Notably, absence of syndecan-1 in a genetic background lacking decorin rescued the attenuated DTH phenotype of Dcn−/− mice. Collectively, these results implicate a role for decorin in mediating DTH responses by influencing polymorphonuclear leukocyte attachment to the endothelium. This occurs via two non-mutually exclusive mechanisms that involve a direct anti-adhesive effect on polymorphonuclear leukocytes and a negative regulation of ICAM-1 and syndecan-1 expression. PMID:22043007

  11. A novel bioactive glass-ceramic for treating dentin hypersensitivity.

    PubMed

    Tirapelli, Camila; Panzeri, Heitor; Soares, Rodrigo Gongalves; Peitl, Oscar; Zanotto, Edgar Dutra

    2010-01-01

    Dentin hypersensitivity (DH) is a painful response to stimulus applied to the open dentinal tubules of a vital tooth. It's a common oral condition, however, without an ideal treatment available yet. This work evaluated in vitro the effect of micron-sized particles from a novel bioactive glass-ceramic (Biosilicate) in occluding open dentinal tubules. A dentin disc model was employed to observe comparatively, using scanning electron microscopy (SEM), dentinal tubule occlusion by different products and deposition of hydroxyl carbonate apatite (HCA) on dentin surface by Biosilicate, after a single application: G1 - Dentifrice with potassium nitrate and fluoride; G2 - Two-step calcium phosphate precipitation treatment; G3 - Water-free gel containing Biosilicate particles (1%); G4 - Biosilicate particles mixed with distilled water in a 1:10 ratio; all of them after 1, 12 and 24 hours of immersion in artificial saliva. Fourier transform infrared spectroscopy (FTIR) was performed to detect HCA formation on dentin discs filled with Biosilicate after 2 minutes, 30 minutes and 12 hours of immersion in artificial saliva. SEM showed a layer of HCA formed on dentin surface after 24 hours by G4. G1, G2 and G3 promoted not total occlusion of open dentinal tubules after 24 hours. FTIR showed HCA precipitation on the dentin surface induced by Biosilicate after 30 minutes. The micron-sized particles from the bioactive glass-ceramic thus were able to induce HCA deposition in open dentinal tubules in vitro. This finding suggests that Biosilicate may provide a new option for treating DH.

  12. Stinging insect hypersensitivity: a practice parameter update 2011.

    PubMed

    Golden, David B K; Moffitt, John; Nicklas, Richard A; Freeman, Theodore; Graft, David F; Reisman, Robert E; Tracy, James M; Bernstein, David; Blessing-Moore, Joann; Cox, Linda; Khan, David A; Lang, David M; Oppenheimer, John; Portnoy, Jay M; Randolph, Christopher; Schuller, Diane E; Spector, Sheldon L; Tilles, Steven A; Wallace, Dana

    2011-04-01

    These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "Stinging insect hypersensitivity: a practice parameter update II." Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or the ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. These parameters are not designed for use by pharmaceutical companies in drug promotion. The Joint Task Force understands that the cost of diagnostic tests and therapeutic agents is an important concern that may appropriately influence the work-up and treatment chosen for a given patient. The Joint Task Force recognizes that the emphasis of our primary recommendations regarding a medication may vary, for example, depending on third party payer issues and product patent expiration dates. However, since a given test or agent's cost is so widely variable, and there is a paucity of pharmacoeconomic data, the Joint Task Force generally does not consider cost when formulating Practice Parameter recommendations. In extraordinary circumstances, when the cost benefit of an intervention is prohibitive as supported by pharmacoeconomic data, commentary may be provided. PMID:21458655

  13. 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.

  14. The search for early markers of plague: evidence for accumulation of soluble Yersinia pestis LcrV in bubonic and pneumonic mouse models of disease.

    PubMed

    Flashner, Yehuda; Fisher, Morly; Tidhar, Avital; Mechaly, Adva; Gur, David; Halperin, Gideon; Zahavy, Eran; Mamroud, Emanuelle; Cohen, Sara

    2010-07-01

    Markers of the early stages of plague, a rapidly progressing deadly disease, are crucial for enabling the onset of an effective treatment. Here, we show that V-antigen protein (LcrV) is accumulated in the serum of Yersinia pestis-infected mice before bacterial colonization of the spleen and dissemination to blood, in a model of bubonic plague. LcrV accumulation is detected earlier than that of F1 capsular antigen, an established marker of disease. In a mouse model of pneumonic plague, LcrV can be determined in the bronchoalveolar lavage fluid somewhat later than F1, but before dissemination of Y. pestis to the blood. Thus, determination of soluble LcrV is suggested as a potential useful tool for monitoring disease progression in both bubonic and pneumonic plague. Moreover, it may be of particular advantage in cases of infections with F1 nonproducing strains.

  15. 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

  16. Nickel hypersensitivity in patients with inferior vena cava filters: case report and literature and MAUDE database review.

    PubMed

    Morshedi, Maud M; Kinney, Thomas B

    2014-08-01

    Placement of a prophylactic retrievable inferior vena cava (IVC) filter was requested in a 73-year-old woman with nickel hypersensitivity resulting in a clinical dilemma. Given that all retrievable filters contain nickel, the published literature and the Manufacturer and User Facility Device Experience (MAUDE) database were reviewed; no documented case of IVC filter placement in a patient with nickel hypersensitivity or reported hypersensitivity reaction in a patient after IVC filter placement could be identified. This article presents the uneventful course of the case described and a review of the literature and recommendations on use of nickel-containing devices in patients with nickel hypersensitivity.

  17. Immunogenicity and protective immunity against bubonic plague and pneumonic plague by immunization of mice with the recombinant V10 antigen, a variant of LcrV.

    PubMed

    DeBord, Kristin L; Anderson, Deborah M; Marketon, Melanie M; Overheim, Katie A; DePaolo, R William; Ciletti, Nancy A; Jabri, Bana; Schneewind, Olaf

    2006-08-01

    In contrast to Yersinia pestis LcrV, the recombinant V10 (rV10) variant (lacking residues 271 to 300) does not suppress the release of proinflammatory cytokines by immune cells. Immunization with rV10 generates robust antibody responses that protect mice against bubonic plague and pneumonic plague, suggesting that rV10 may serve as an improved plague vaccine.

  18. Dentin hypersensitivity: from diagnosis to a breakthrough therapy for everyday sensitivity relief.

    PubMed

    Cummins, Diane

    2009-01-01

    This paper provides an overview of the current knowledge of diagnosis, epidemiology, etiology, and clinical management of dentin hypersensitivity. It summarizes technical approaches to relieve sensitivity in professional and home-use products, with emphasis on the clinical evidence for the efficacy of desensitizing toothpaste, and introduces a new innovative dentifrice technology containing 8% arginine, calcium carbonate, and 1450 ppm fluoride. Dentin hypersensitivity is characterized by short, sharp pain arising from exposed dentin in response to external stimuli which cannot be ascribed to any other form of dental defect or disease. The hydrodynamic theory proposes that pain-producing stimuli cause a change in dentin fluid flow that activates intra-dental nerve fibers, via a mechanoreceptor response, to cause pain. To be hypersensitive, dentin must be exposed and dentin tubules must be open to external stimuli and patent at the pulp. Gingival recession is the primary cause of dentin exposure, and a major predisposing factor for dentin hypersensitivity. Dentin hypersensitivity is a prevalent condition. It has been reported to afflict 15-20% of the adult population, typically 20 to 50-year-olds, with peak incidence between 30 and 39 years. Some studies have reported higher prevalence levels of up to 57%. The incidence of dentin hypersensitivity is expected to rise with changing diets, and as caries and periodontal disease prevention result in improved oral health status, and retention and functionality of the dentition. Treatments to relieve dentin hypersensitivity are based on interruption of the neural response to pain stimuli or occlusion of open tubules to block the hydrodynamic mechanism. Effective and robust dentin occlusion offers the greatest prospect for instant and lasting relief of dentin hypersensitivity. In particular, materials which can coat exposed dentin surfaces, in addition to plugging and sealing open dentin tubules, offer the intriguing

  19. Dentin hypersensitivity: from diagnosis to a breakthrough therapy for everyday sensitivity relief.

    PubMed

    Cummins, Diane

    2009-01-01

    This paper provides an overview of the current knowledge of diagnosis, epidemiology, etiology, and clinical management of dentin hypersensitivity. It summarizes technical approaches to relieve sensitivity in professional and home-use products, with emphasis on the clinical evidence for the efficacy of desensitizing toothpaste, and introduces a new innovative dentifrice technology containing 8% arginine, calcium carbonate, and 1450 ppm fluoride. Dentin hypersensitivity is characterized by short, sharp pain arising from exposed dentin in response to external stimuli which cannot be ascribed to any other form of dental defect or disease. The hydrodynamic theory proposes that pain-producing stimuli cause a change in dentin fluid flow that activates intra-dental nerve fibers, via a mechanoreceptor response, to cause pain. To be hypersensitive, dentin must be exposed and dentin tubules must be open to external stimuli and patent at the pulp. Gingival recession is the primary cause of dentin exposure, and a major predisposing factor for dentin hypersensitivity. Dentin hypersensitivity is a prevalent condition. It has been reported to afflict 15-20% of the adult population, typically 20 to 50-year-olds, with peak incidence between 30 and 39 years. Some studies have reported higher prevalence levels of up to 57%. The incidence of dentin hypersensitivity is expected to rise with changing diets, and as caries and periodontal disease prevention result in improved oral health status, and retention and functionality of the dentition. Treatments to relieve dentin hypersensitivity are based on interruption of the neural response to pain stimuli or occlusion of open tubules to block the hydrodynamic mechanism. Effective and robust dentin occlusion offers the greatest prospect for instant and lasting relief of dentin hypersensitivity. In particular, materials which can coat exposed dentin surfaces, in addition to plugging and sealing open dentin tubules, offer the intriguing

  20. Virus Infections Incite Pain Hypersensitivity by Inducing Indoleamine 2,3 Dioxygenase

    PubMed Central

    Huang, Lei; Ou, Rong; Rabelo de Souza, Guilherme; Cunha, Thiago M.; Lemos, Henrique; Mohamed, Eslam; Li, Lingqian; Pacholczyk, Gabriela; Randall, Janice; Munn, David H.; Mellor, Andrew L.

    2016-01-01

    Increased pain sensitivity is a comorbidity associated with many clinical diseases, though the underlying causes are poorly understood. Recently, chronic pain hypersensitivity in rodents treated to induce chronic inflammation in peripheral tissues was linked to enhanced tryptophan catabolism in brain mediated by indoleamine 2,3 dioxygenase (IDO). Here we show that acute influenza A virus (IAV) and chronic murine leukemia retrovirus (MuLV) infections, which stimulate robust IDO expression in lungs and lymphoid tissues, induced acute or chronic pain hypersensitivity, respectively. In contrast, virus-induced pain hypersensitivity did not manifest in mice lacking intact IDO1 genes. Spleen IDO activity increased markedly as MuLV infections progressed, while IDO1 expression was not elevated significantly in brain or spinal cord (CNS) tissues. Moreover, kynurenine (Kyn), a tryptophan catabolite made by cells expressing IDO, incited pain hypersensitivity in uninfected IDO1-deficient mice and Kyn potentiated pain hypersensitivity due to MuLV infection. MuLV infection stimulated selective IDO expression by a discreet population of spleen cells expressing both B cell (CD19) and dendritic cell (CD11c) markers (CD19+ DCs). CD19+ DCs were more susceptible to MuLV infection than B cells or conventional (CD19neg) DCs, proliferated faster than B cells from early stages of MuLV infection and exhibited mature antigen presenting cell (APC) phenotypes, unlike conventional (CD19neg) DCs. Moreover, interactions with CD4 T cells were necessary to sustain functional IDO expression by CD19+ DCs in vitro and in vivo. Splenocytes from MuLV-infected IDO1-sufficient mice induced pain hypersensitivity in uninfected IDO1-deficient recipient mice, while selective in vivo depletion of DCs alleviated pain hypersensitivity in MuLV-infected IDO1-sufficient mice and led to rapid reduction in splenomegaly, a hallmark of MuLV immune pathogenesis. These findings reveal critical roles for CD19+ DCs

  1. Titration of human cytomegalovirus (HCMV) DNA in urine by combined use of PCR and microplate hybridization in a renal transplant patient with HCMV pneumonitis.

    PubMed

    Meigata, K; Hondo, R; Fujima, A; Shinkai-Shibata, M; Itoh, S; Kikuchi, K; Ando, Y; Ichikawa, N; Nomura, Y; Watanabe, K; Degawa, H; Beck, Y; Tomikawa, S; Nagao, T; Uchida, H

    1996-06-01

    We titrated human cytomegalovirus (HCMV) DNA in urine specimens obtained from 14 healthy individuals and a renal transplant patient with HCMV pneumonitis by modifying the method for titration of varicella-zoster virus DNA previously described (1,2). Of 14 HCMV seropositive healthy individuals, 13 had HCMV DNA under the detection limit of 10(2.0) copies/ml, whereas one person had 10(2.0) copies/ml. The viral DNA in urine samples was at a low level in healthy individuals with latent infection. In a case with HCMV pneumonitis after renal transplantation, the amount of HCMV DNA in urine gradually increased from the level under 10(2.0) copies/ml and reached a peak of 10(4.7) copies/ml one month prior to the manifestation of pneumonitis. It, thereafter, decreased with the course of clinical remission, and finally settled at under 10(2.0) copies/ml. Serial titrations of HCMV DNA in urine specimens proved to be useful in identifying recipients at risk of developing active HCMV infection after renal transplantation and as a guide for treatment of patients.

  2. Nickel hypersensitivity and orthodontic treatment: a systematic review and meta-analysis.

    PubMed

    Gölz, Lina; Papageorgiou, Spyridon N; Jäger, Andreas

    2015-07-01

    Nickel-containing alloys are widely used in orthodontic appliances, even though nickel is by far the most common contact allergen. However, the scientific evidence concerning allergic reactions to nickel in orthodontic patients has not been evaluated systematically. The objective of this study was to investigate whether the prevalence of nickel hypersensitivity is affected by orthodontic treatment. Unrestricted electronic and manual searches were performed until July 2013 for human clinical studies assessing orthodontic treatment and nickel hypersensitivity. Methodological limitations were evaluated with the Downs and Black tool. Crude and adjusted odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated from random-effects meta-analyses, followed by subgroup and sensitivity analyses. Thirty studies were included in the review, and 24 datasets with 10 184 patients in the meta-analyses. Orthodontic treatment had no significant effect on nickel hypersensitivity (n = 11; crude OR 0.99; 95%CI: 0.78-1.25; p = 0.914). However, when confounding from factors such as sex and piercings was taken into account, orthodontic treatment was associated with a lower risk of hypersensitivity (n = 1; adjusted OR 0.60; 95%CI: 0.40-0.80; p < 0.001). This was even more pronounced when orthodontic treatment was performed prior to piercing (n = 7; crude OR 0.35; 95%CI: 0.24-0.50; p < 0.001). Orthodontic treatment seems to have a protective role against nickel hypersensitivity, especially when it precedes piercings.

  3. Hypersensitivity reactions to metallic implants - diagnostic algorithm and suggested patch test series for clinical use.

    PubMed

    Schalock, Peter C; Menné, Torkil; Johansen, Jeanne D; Taylor, James S; Maibach, Howard I; Lidén, Carola; Bruze, Magnus; Thyssen, Jacob P

    2012-01-01

    Cutaneous and systemic hypersensitivity reactions to implanted metals are challenging to evaluate and treat. Although they are uncommon, they do exist, and require appropriate and complete evaluation. This review summarizes the evidence regarding evaluation tools, especially patch and lymphocyte transformation tests, for hypersensitivity reactions to implanted metal devices. Patch test evaluation is the gold standard for metal hypersensitivity, although the results may be subjective. Regarding pre-implant testing, those patients with a reported history of metal dermatitis should be evaluated by patch testing. Those without a history of dermatitis should not be tested unless considerable concern exists. Regarding post-implant testing, a subset of patients with metal hypersensitivity may develop cutaneous or systemic reactions to implanted metals following implant. For symptomatic patients, a diagnostic algorithm to guide the selection of screening allergen series for patch testing is provided. At a minimum, an extended baseline screening series and metal screening is necessary. Static and dynamic orthopaedic implants, intravascular stent devices, implanted defibrillators and dental and gynaecological devices are considered. Basic management suggestions are provided. Our goal is to provide a comprehensive reference for use by those evaluating suspected cutaneous and systemic metal hypersensitivity reactions.

  4. Hypersensitivity reaction studies of a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation.

    PubMed

    Wang, Hongbo; Cheng, Guang; Du, Yuan; Ye, Liang; Chen, Wenzhong; Zhang, Leiming; Wang, Tian; Tian, Jingwei; Fu, Fenghua

    2013-03-01

    The commercial drug paclitaxel (Taxol) may introduce hypersensitivity reactions associated with the polyethoxylated castor oil-ethanol solvent. To overcome these problems, we developed a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation, known as Lipusu. In this study, we performed in vitro and in vivo experiments to compare the safety profiles of Lipusu and Taxol, with special regard to hypersensitivity reactions. First, Swiss mice were used to determine the lethal dosages, and then to evaluate hypersensitivity reactions, followed by histopathological examination and enzyme-linked immunosorbent assays (ELISAs) of serum SC5b-9 and lung histamine. Additionally, healthy human serum was used to analyze in vitro complement activation. Finally, an MTT assay was used to determine the in vitro anti-proliferation activity. Our data clearly showed that Lipusu displayed a much higher safety margin and did not induce hypersensitivity or hypersensitivity-related lung lesions, which may be associated with the fact that Lipusu did not activate complement or increase histamine release in vivo. Moreover, Lipusu did not promote complement activation in healthy human serum in vitro, and demonstrated anti-proliferative activity against human cancer cells, similar to that of Taxol. Therefore, the improved formulation of paclitaxel, which exhibited a much better safety profile and comparable cytotoxic activity to Taxol, may bring a number of benefits to cancer patients.

  5. A case of chlorpheniramine maleate-induced hypersensitivity with aspirin intolerance.

    PubMed

    Kim, Min-Hye; Lee, Sang-Min; Lee, So-Hee; Kwon, Hyouk-Soo; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young; Chang, Yoon-Seok

    2011-01-01

    Antihistamines are commonly used to treat allergic disease, such as allergic rhinitis, urticaria, and angioedema. Although several previous reports describe hypersensitivity to antihistamines such as cetirizine and hydroxyzine, documented cases of chlorpheniramine hypersensitivity are extremely rare. Here, we report the case of a 45-year-old Korean woman who presented with urticaria after ingesting a cold medication. Over the previous 5 years, she had also experienced a food allergy to crab and shrimp, allergic rhinitis, and repeated urticaria after ingesting cold medication. Provocation with aspirin elicited generalized urticaria. Intravenous chlorpheniramine and methylprednisolone was injected for symptom control, but in fact appeared to aggravate urticaria. A second round of skin and provocation tests for chlorpheniramine and methylprednisolone showed positive results only for chlorpheniramine. She was diagnosed with aspirin intolerance and chlorpheniramine hypersensitivity, and was instructed to avoid these drugs. To date, this is the second of only two cases of chlorpheniramine-induced type I hypersensitivity with aspirin intolerance. Although the relationship between aspirin intolerance and chlorpheniramine-induced type I hypersensitivity is unclear, physicians should be aware of the possibility of urticaria or other allergic reactions in response to antihistamines.

  6. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson's Disease

    PubMed Central

    Wang, Bing; Chen, Li-Hua

    2016-01-01

    In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain. PMID:27747105

  7. Low-level laser therapy of dentin hypersensitivity: a short-term clinical trial.

    PubMed

    Orhan, Kaan; Aksoy, Umut; Can-Karabulut, Deniz C; Kalender, Atakan

    2011-09-01

    The aim of this study was to evaluate low-level laser therapy in cervical dentin hypersensitivity. A randomized controlled clinical trial was conducted with a total of 64 teeth. Dentin desensitizer and diode laser were applied on the cervical dentin surfaces. Distilled water and placebo laser was used as the placebo groups. The irradiance used was 4 J/cm(2) per treatment site. The baseline measurement of hypersensitivity was made by using visual analog scale (VAS). Twenty-four hours and 7 days after the application of desensitizer, diode laser and placebo groups, a new VAS analysis was conducted for the patients' sensitivity level. The mean pain scores of placebo groups were significantly higher than the desensitizer's and diode laser's mean scores (ANOVA, p < 0.05). The VAS analysis revealed a significant decrease in dentin hypersensitivity in 7 days with the use of the desensitizer and low-level laser therapy and no statistically significant difference was observed between these two treatments (p > 0.05). Although low-level laser and glutaraldehyde containing desensitizer present distinct modes of action, experimental agents caused a significant reduction of dentin hypersensitivity without showing secondary effects, not irritating the pulp or causing pain, not discoloring or staining the teeth, and not irritating the soft tissues at least for a period of 1 week with no drawbacks regarding handling and/or ease of application. Low-level laser therapy and desensitizer application had displayed similar effectiveness in reducing moderate dentin hypersensitivity.

  8. DNase I hypersensitive sites within the inducible qa gene cluster of Neurospora crassa.

    PubMed Central

    Baum, J A; Giles, N H

    1986-01-01

    DNase I hypersensitive regions were mapped within the 17.3-kilobase qa (quinic acid) gene cluster of Neurospora crassa. The 5'-flanking regions of the five qa structural genes and the two qa regulatory genes each contain DNase I hypersensitive sites under noninducing conditions and generally exhibit increases in DNase I cleavage upon induction of transcription with quinic acid. The two large intergenic regions of the qa gene cluster appear to be similarly organized with respect to the positions of constitutive and inducible DNase I hypersensitive sites. Inducible hypersensitive sites on the 5' side of one qa gene, qa-x, appear to be differentially regulated. Employing these and previously published data, we have identified a conserved sequence element that may mediate the activator function of the qa-1F regulatory gene. Variants of the 16-base-pair consensus sequence are consistently found within DNase I-protected regions adjacent to inducible DNase I hypersensitive sites within the gene cluster. Images PMID:2944110

  9. Anti-inflammatory and immune-regulatory mechanisms prevent contact hypersensitivity to Arnica montana L.

    PubMed

    Lass, Christian; Vocanson, Marc; Wagner, Steffen; Schempp, Christoph M; Nicolas, Jean-Francois; Merfort, Irmgard; Martin, Stefan F

    2008-10-01

    Sesquiterpene lactones (SL), secondary plant metabolites from flowerheads of Arnica, exert anti-inflammatory effects mainly by preventing nuclear factor (NF)-kappaB activation because of alkylation of the p65 subunit. Despite its known immunosuppressive action, Arnica has been classified as a plant with strong potency to induce allergic contact dermatitis. Here we examined the dual role of SL as anti-inflammatory compounds and contact allergens in vitro and in vivo. We tested the anti-inflammatory and allergenic potential of SL in the mouse contact hypersensitivity model. We also used dendritic cells to study the activation of NF-kappaB and the secretion of interleukin (IL)-12 in the presence of different doses of SL in vitro. Arnica tinctures and SL potently suppressed NF-kappaB activation and IL-12 production in dendritic cells at high concentrations, but had immunostimulatory effects at low concentrations. Contact hypersensitivity could not be induced in the mouse model, even when Arnica tinctures or SL were applied undiluted to inflamed skin. In contrast, Arnica tinctures suppressed contact hypersensitivity to the strong contact sensitizer trinitrochlorobenzene and activation of dendritic cells. However, contact hypersensitivity to Arnica tincture could be induced in acutely CD4-depleted MHC II knockout mice. These results suggest that induction of contact hypersensitivity by Arnica is prevented by its anti-inflammatory effect and immunosuppression as a result of immune regulation in immunocompetent mice.

  10. Effect of Two Desensitizing Agents in Reducing Dentin Hypersensitivity: An in-vivo Comparative Clinical Trial

    PubMed Central

    Torwane, Nilesh Arjun; Hongal, Sudhir; Goel, Pankaj; B.R, Chandrashekhar; Jain, Manish; Saxena, Eshani; Gouraha, Abhishek; Yadav, Sourabh

    2013-01-01

    Objective: A randomized, double blind, split mouth, controlled clinical trial was conducted to evaluate the effect of two desensitizing agents on reduction of Dentin Hypersensitivity (DH). Material and Methodology: A sample of 73 teeth from 13 patients, among which at least 3 teeth had dentin hypersensitivity, was randomly allocated into 3 treatment groups: Group A: treated with 30% ethenolic extract of Indian Propolis, Group B: treated with GC tooth mousse, and Group C: treated with sterile water. A Verbal Rating Scale (VRS) was used to record the degree of hypersensitivity, based on patient’s response to tactile and air blast stimuli. The baseline scores were obtained. Each intervention group received applications of their respective agents consecutively on 1st, 7th, 14th and 21st days. After each application, the scores were recorded. Results: Both the 30% Indian Propolis and GC tooth mousse showed significant reductions in dentin hypersensitivity. Conclusion: GC tooth mousse was found to be significantly better in reducing the dentinal hypersensitivity as compared to Propolis and sterile water (p< 0.01). PMID:24179939

  11. Observations on dentine hypersensitivity in general dental practices in the United Arab Emirates

    PubMed Central

    Al-Khafaji, Hasanain

    2013-01-01

    Dentine hypersensitivity is a common clinical finding with a wide variation in prevalence values and etiological factors. The objective of this cross-sectional study was to investigate the prevalence and some etiological factors of dentine hypersensitivity of Emirati patients visiting general dental clinics in the United Arab Emirates (UAE) over a period of three calendar months. Materials and Methods: Six general dental practitioners examined 204 Emirati patients over a period of three calendar months and patients who had dentine hypersensitivity diagnosed were questioned further about their smoking habits and the frequency, severity, and duration of their pain. Furthermore, cervical tooth surface loss was noted. Results: A total of 55 patients were diagnosed as having dentine hypersensitivity, giving a prevalence figure of 27%. The most common teeth affected were the lower anterior teeth. Conclusions: The prevalence of dentine hypersensitivity in Emirati patients visiting a general dental clinic in the UAE was 27%. The most common etiology appeared to be the loss of cervical tooth surface structure. PMID:24932110

  12. Clinical food hypersensitivity: the relevance of duodenal immunoglobulin E-positive cells.

    PubMed

    Caffarelli, C; Romanini, E; Caruana, P; Street, M E; de' Angelis, G

    1998-10-01

    Owing to poor reliability of laboratory tests, diagnosis of food allergy is based on clinical response to double-blind placebo-controlled food challenge. The aim of the present study was to assess the value of duodenal IgE-positive cells in the diagnosis of food allergy. Thirty-one children with a history of possible food allergy underwent duodenal biopsies, skin prick tests, and measurement of serum IgE antibodies, and were put on an elimination diet followed by food challenge. Open food challenges were performed in patients under 12 mo of age, and double-blind placebo-controlled challenges were for suspected foods. On the basis of clinical food hypersensitivity, patients were divided into two groups. Group 1 consisted of 13 children with food allergy. Thirteen of 20 positive provocations elicited reactions within 12 h from the end of the challenge, seven later. Group 2 was the control group and included 18 patients with negative food challenges. The number of IgE-positive cells in biopsy specimens was significantly more elevated in group 1 with respect to group 2 (153.24 +/- 83.13 versus 18.4 +/- 18.9; p < 0.01). Total serum IgE levels were elevated compared with that of the control group (p < 0.01) and correlated with the number of IgE-positive cells (p < 0.001, r = 0.62). Enhanced IgE-containing cells were found in all delayed reactors, but about one-third had negative skin prick tests or specific serum IgE antibodies to the offending foods. Our results showed that systemic reactions to foods are associated with an IgE-mediated response in the duodenal mucosa. Larger studies would be required to assess the predictive value of an increased number of IgE-positive cells in the diagnosis of allergy to food, especially in children with delayed reactions.

  13. Analysis of deep tissue hypersensitivity to pressure pain in professional pianists with insidious mechanical neck pain

    PubMed Central

    2011-01-01

    Background The aim of this study was to investigate whether pressure pain hyperalgesia is a feature of professional pianists suffering from neck pain as their main playing-related musculoskeletal disorder. Methods Twenty-three active expert pianists, 6 males and 17 females (age: 36 ± 12 years) with insidious neck pain and 23 pianists, 9 males and 14 females (age: 38 ± 10 years) without neck pain the previous year were recruited. A numerical pain rate scale, Neck Disability Index, hand size and pressure pain thresholds (PPT) were assessed bilaterally over the C5-C6 zygapophyseal joint, deltoid muscle, the second metacarpal and the tibialis anterior muscle in a blinded design. Results The results showed that PPT levels were significantly decreased bilaterally over the second metacarpal and tibialis anterior muscles (P < 0.05), but not over C5-C6 zygapophyseal joint and deltoid muscle (P > 0.10), in pianists with neck pain as compared to healthy pianists. Pianists with neck pain had a smaller (P < 0.05) hand size (mean: 181.8 ± 11.8) as compared to pianists without neck pain (mean: 188. 6 ± 13.1). PPT over the tibialis anterior muscles was negatively correlated with the intensity of neck pain. Conclusions Our findings revealed pressure pain hypersensitivity over distant non-symptomatic distant points but not over the symptomatic areas in pianists suffering from neck pain. In addition, pianists with neck pain also had smaller hand size than those without neck pain. Future studies are needed to further determine the relevance of these findings in the clinical course of neck pain as playing-related musculoskeletal disorder in professional pianists. PMID:22111912

  14. Genome-wide detection of DNase I hypersensitive sites in single cells and FFPE tissue samples.

    PubMed

    Jin, Wenfei; Tang, Qingsong; Wan, Mimi; Cui, Kairong; Zhang, Yi; Ren, Gang; Ni, Bing; Sklar, Jeffrey; Przytycka, Teresa M; Childs, Richard; Levens, David; Zhao, Keji

    2015-12-01

    DNase I hypersensitive sites (DHSs) provide important information on the presence of transcriptional regulatory elements and the state of chromatin in mammalian cells. Conventional DNase sequencing (DNase-seq) for genome-wide DHSs profiling is limited by the requirement of millions of cells. Here we report an ultrasensitive strategy, called single-cell DNase sequencing (scDNase-seq) for detection of genome-wide DHSs in single cells. We show that DHS patterns at the single-cell level are highly reproducible among individual cells. Among different single cells, highly expressed gene promoters and enhancers associated with multiple active histone modifications display constitutive DHS whereas chromatin regions with fewer histone modifications exhibit high variation of DHS. Furthermore, the single-cell DHSs predict enhancers that regulate cell-specific gene expression programs and the cell-to-cell variations of DHS are predictive of gene expression. Finally, we apply scDNase-seq to pools of tumour cells and pools of normal cells, dissected from formalin-fixed paraffin-embedded tissue slides from patients with thyroid cancer, and detect thousands of tumour-specific DHSs. Many of these DHSs are associated with promoters and enhancers critically involved in cancer development. Analysis of the DHS sequences uncovers one mutation (chr18: 52417839G>C) in the tumour cells of a patient with follicular thyroid carcinoma, which affects the binding of the tumour suppressor protein p53 and correlates with decreased expression of its target gene TXNL1. In conclusion, scDNase-seq can reliably detect DHSs in single cells, greatly extending the range of applications of DHS analysis both for basic and for translational research, and may provide critical information for personalized medicine. PMID:26605532

  15. Genome-wide Detection of DNase I Hypersensitive Sites in Single Cells and FFPE Samples

    PubMed Central

    Jin, Wenfei; Tang, Qingsong; Wan, Mimi; Cui, Kairong; Zhang, Yi; Ren, Gang; Ni, Bing; Sklar, Jeffrey; Przytycka, Teresa M.; Childs, Richard; Levens, David; Zhao, Keji

    2015-01-01

    DNase I hypersensitive sites (DHSs) provide important information on the presence of transcriptional regulatory elements and the state of chromatin in mammalian cells1–3. Conventional DNase-Seq for genome-wide DHSs profiling is limited by the requirement of millions of cells4,5. Here we report an ultrasensitive strategy, called Pico-Seq, for detection of genome-wide DHSs in single cells. We show that DHS patterns at the single cell level are highly reproducible among individual cells. Among different single cells, highly expressed gene promoters and the enhancers associated with multiple active histone modifications display constitutive DHS while chromatin regions with fewer histone modifications exhibit high variation of DHS. Furthermore, the single-cell DHSs predict enhancers that regulate cell-specific gene expression programs and the cell-to-cell variations of DHS are predictive of gene expression. Finally, we apply Pico-Seq to pools of tumor cells and pools of normal cells, dissected from formalin-fixed paraffin-embedded (FFPE) tissue slides from thyroid cancer patients, and detect thousands of tumor-specific DHSs. Many of these DHSs are associated with promoters and enhancers critically involved in cancer development. Analysis of the DHS sequences uncovers one single-nucleotide variant (chr18:52417839 G>C) in the tumor cells of a follicular thyroid carcinoma patient, which affects the binding of the tumor suppressor protein p53 and correlates with decreased expression of its target gene TXNL1. In conclusion, Pico-Seq can reliably detect DHSs in single cells, greatly extending the range of applications of DHS analysis for both basic and translational research and may provide critical information for personalized medicine. PMID:26605532

  16. Immune cell populations in cutaneous delayed-type hypersensitivity

    PubMed Central

    1983-01-01

    Delayed-type hypersensitivity (DTH) is a prototypic T lymphocyte- mediated response to antigenic challenge. In this study, mononuclear cells infiltrating the skin during cutaneous response to tuberculin in presensitized human subjects (responders) and nonimmune controls were identified using monoclonal antibodies by indirect immunofluorescence. In both responders and controls the infiltrate consisted mainly of T lymphocytes (T11+ and OKT3+) and monocytes (OKM1+, 63D3+, Mo2+) which initially accumulated in proximity to small blood vessels and later infiltrated the interstitial dermis and epidermis. More T lymphocytes reacted with OKT4 than with OKT8. 6 h after tuberculin the ratio of OKT4/OKT8 in tissue from responders exceeded that in blood, whereas in tissues studied at 15-48 h and in all control tissues those ratios in blood and tissue were similar. Evidence of T lymphocyte activation was sought using monoclonal antibodies anti-Tac, OKT9, and OKT10. In responders but not in controls the proportion of infiltrating cells reactive with these antibodies increased during the course of DTH. The presence of activated T lymphocytes in tissue was not associated with a comparable increase in peripheral blood cell populations identified by anti-Tac and OKT10. Studies using anti-B1, Leu-7, and anti-IgD/IgM revealed comparatively few reactive cells. Dual-labeling studies demonstrated that most Leu-7--reactive cells also bound T11 while fewer bound OKM1 or OKT8 and that cells reactive with OKIa1 and T11 constituted largely nonoverlapping populations. Specific patterns of reactivity were not observed when tissues were stained with anti-human C3, or poly C9-MA, a monoclonal antibody reactive with a neoantigen on polymerized C9 of the membrane attack complex of complement. The number of epidermal Langerhans cells identified by OKT6 was similar in responders and controls. Thus, the cutaneous response to tuberculin in sensitized individuals is characterized by early enrichment of

  17. Spinal transient receptor potential ankyrin 1 channel contributes to central pain hypersensitivity in various pathophysiological conditions in the rat.

    PubMed

    Wei, Hong; Koivisto, Ari; Saarnilehto, Marja; Chapman, Hugh; Kuokkanen, Katja; Hao, Bin; Huang, Jin-Lu; Wang, Yong-Xiang; Pertovaara, Antti

    2011-03-01

    The transient receptor potential ankyrin 1 (TRPA1) ion channel is expressed on nociceptive primary afferent neurons. On the proximal nerve ending within the spinal dorsal horn, TRPA1 regulates transmission to spinal interneurons, and thereby pain hypersensitivity. Here we assessed whether the contribution of the spinal TRPA1 channel to pain hypersensitivity varies with the experimental pain model, properties of test stimulation or the behavioral pain response. The antihypersensitivity effect of intrathecally (i.t.) administered Chembridge-5861528 (CHEM; a selective TRPA1 channel antagonist; 5-10μg) was determined in various experimental models of pain hypersensitivity in the rat. In spinal nerve ligation and rapid eye movement (REM) sleep deprivation models, i.t. CHEM attenuated mechanical hypersensitivity. Capsaicin-induced secondary (central) but not primary (peripheral) mechanical hypersensitivity was also reduced by i.t. administration of CHEM or A-967079, another TRPA1 channel antagonist. Formalin-induced secondary mechanical hypersensitivity, but not spontaneous pain, was suppressed by i.t. CHEM. Moreover, mechanical hypersensitivity induced by cholekystokinin in the rostroventromedial medulla was attenuated by i.t. pretreatment with CHEM. Independent of the model, the antihypersensitivity effect induced by i.t. CHEM was predominant on responses evoked by low-intensity stimuli (⩽6g). CHEM (10μg i.t.) failed to attenuate pain behavior in healthy controls or mechanical hypersensitivities induced by i.t. administrations of a GABA(A) receptor antagonist, or NMDA or 5-HT(3) receptor agonists. Conversely, i.t. administration of a TRPA1 channel agonist, cinnamon aldehyde, induced mechanical hypersensitivity. The results indicate that the spinal TRPA1 channel exerts an important role in secondary (central) pain hypersensitivity to low-intensity mechanical stimulation in various pain hypersensitivity conditions. The spinal TRPA1 channel provides a promising target

  18. Chlamydial disease pathogenesis. Ocular hypersensitivity elicited by a genus-specific 57-kD protein

    PubMed Central

    1989-01-01

    Recurrent or persistent infections with Chlamydia trachomatis are thought to provide the antigenic stimulus for the chronic inflammation associated with blinding trachoma. We used the guinea pig model of inclusion conjunctivitis to identify chlamydial antigens that may be involved in this deleterious immune response. We purified from chlamydial elementary bodies a genus-specific 57-kD protein that elicited an ocular hypersensitivity response when placed topically onto the conjunctiva of ocular immune guinea pigs. This response was characterized by a predominantly mononuclear macrophage and lymphocyte cellular infiltrate of the submucosal epithelium. The clinical and histological findings were consistent with those of a delayed hypersensitivity response. These data demonstrated that the 57-kD chlamydial protein was a potent stimulator of ocular delayed hypersensitivity. Our findings may be critical to understanding the pathogenesis of the debilitating chlamydial diseases associated with chronic inflammation, such as trachoma and many urogenital syndromes. PMID:2926323

  19. Evaluation of Dentifrice Containing Nano-hydroxyapatite for Dentinal Hypersensitivity: A Randomized Controlled Trial

    PubMed Central

    Gopinath, Nithin Manchery; John, Joseph; Nagappan, N; Prabhu, S; Kumar, E Senthil

    2015-01-01

    Background: This randomized, double-blind, parallel arm study was carried out to evaluate and compare the effectiveness between nano-hydroxyapatite (HAP) and a benchmark dentifrice in reducing dentin hypersensitivity. Materials and Methods: About 36 patients were selected, randomly divided into two groups and was evaluated clinically using three different stimuli, i.e., tactile, air blast, and cold water test. The patient’s responses to various stimuli were recorded using a visual analog scale at baseline and after 4 weeks. Results: Statistical analysis was done using unpaired and paired t-tests. It was seen that patients treated in both groups showed significant reductions scores across all sensitivity measures at the end of 4 weeks. Conclusion: The HAP containing toothpaste was effective in reducing dentin hypersensitivity with pre-existing benchmark toothpaste tested and hence can be advocated in the management of hypersensitivity. PMID:26464553

  20. Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity.

    PubMed

    Yin, Shijin; Luo, Jialie; Qian, Aihua; Du, Junhui; Yang, Qing; Zhou, Shentai; Yu, Weihua; Du, Guangwei; Clark, Richard B; Walters, Edgar T; Carlton, Susan M; Hu, Hongzhen

    2013-09-01

    Retinoids are structurally related derivatives of vitamin A and are required for normal vision as well as cell proliferation and differentiation. Clinically, retinoids are effective in treating many skin disorders and cancers. Application of retinoids evokes substantial irritating side effects, including pain and inflammation; however, the precise mechanisms accounting for the sensory hypersensitivity are not understood. Here we show that both naturally occurring and synthetic retinoids activate recombinant or native transient receptor potential channel vanilloid subtype 1 (TRPV1), an irritant receptor for capsaicin, the pungent ingredient of chili peppers. In vivo, retinoids produced pain-related behaviors that were either eliminated or significantly reduced by genetic or pharmacological inhibition of TRPV1 function. These findings identify TRPV1 as an ionotropic receptor for retinoids and provide cellular and molecular insights into retinoid-evoked hypersensitivity. These findings also suggest that selective TRPV1 antagonists are potential therapeutic drugs for treating retinoid-induced sensory hypersensitivity. PMID:23925292