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Sample records for hypersensitivity pneumonitis correlation

  1. Hypersensitivity Pneumonitis

    MedlinePlus

    ... Hypersensitivity Pneumonitis Also known as extrinsic allergic alveolitis, bird fancier’s lung, farmer’s lung, hot tub lung, and humidifier lung. Hypersensitivity pneumonitis is a rare immune system disorder that affects the lungs. It occurs in ...

  2. 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 . ...

  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. © 2016 The Author(s).

  4. 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

  5. Rituximab-Induced Hypersensitivity Pneumonitis

    PubMed Central

    Tonelli, Adriano R.; Lottenberg, Richard; Allan, Robert W.; Sriram, P.S.

    2009-01-01

    Rituximab is a chimeric anti-CD20 monoclonal antibody used to treat CD20+ non-Hodgkin's lymphoma. Although pulmonary adverse reactions such as cough, rhinitis, bronchospasm, dyspnea and sinusitis are relatively common, other respiratory conditions like cryptogenic organizing pneumonia, interstitial pneumonitis and diffuse alveolar hemorrhage have rarely been reported. Only 2 possible cases of rituximab-associated hypersensitivity pneumonitis have been described to date. We present a case of hypersensitivity pneumonitis with classic radiographic and histopathologic findings in a patient treated with rituximab who responded to prednisone. PMID:18843175

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

    PubMed

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

    2005-01-01

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

  7. 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

  8. 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

  9. Hypersensitivity pneumonitis due to an ultrasonic humidifier.

    PubMed

    Alvarez-Fernández, J A; Quirce, S; Calleja, J L; Cuevas, M; Losada, E

    1998-02-01

    We describe a woman with hypersensitivity pneumonitis that was related to using a home ultrasonic humidifier. A micronodular infiltrate was seen in her chest radiograph. The inhalation challenge test was performed with the humidifier, and she exhibited a positive response. The cultures of the humidifier water grew Candida albicans, Rhodotorula spp., and Aspergillus spp. The test for precipitating antibodies against the humidifier water gave a positive response, and specific IgG, IgM, and IgA antibodies against extracts of A. fumigatus, C. albicans, and Rhodotorula spp. were demonstrated in the patient's serum by ELISA. A strong, dose-dependent inhibition of Rhodotorula IgG-ELISA by humidifier water was observed, suggesting that Rhodotorula might be the cause of hypersensitivity pneumonitis in this patient.

  10. Hypersensitivity pneumonitis associated with environmental mycobacteria.

    PubMed

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

    2005-06-01

    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.

  11. 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

  12. Phenytoin-induced acute hypersensitivity pneumonitis.

    PubMed

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

    2015-01-01

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

  13. Hypersensitivity pneumonitis induced by Shiitake mushroom spores.

    PubMed

    Ampere, Alexandre; Delhaes, Laurence; Soots, Jacques; Bart, Frederic; Wallaert, Benoit

    2012-08-01

    Hypersensitivity pneumonitis (HP) is a pulmonary granulomatosis involving an immunoallergic mechanism caused by chronic inhalation of antigens, most frequently organic substances, as well as chemicals. We report the first European case of hypersensitivity pneumonitis due to the inhalation of Shiitake mushroom spores. A 37-year-old French Caucasian man with a one-month history of persistent dry cough, shortness of breath and loss of weight was admitted to our hospital on December 2010. Anamnesis showed he was involved in mushroom production beginning in the summer of 2010. His temperature on admission was 36.6°C and he had a normal blood pressure (135/90 mmHg). Bilateral fine crackles were audible in the base of both lungs. Pulmonary function tests showed a mild restrictive pattern with decreased DLco and a PaO(2) of 65 mmHg, Chest CT scan revealed reticulo-nodular shadows, slight ground glass opacities, liner atelectasis, and subpleural opacities in both lung fields. Bronchoscopy was normal but cytological examination of BAL revealed a predominant lymphocytosis (55%). Serum precipitins to the Shiitake mushroom spores were positive (3 precipitins arcs with high intensity) and as a result we advised the patient to cease his mushroom production activities. The diagnosis of hypersensitivity pneumonitis due to inhalation of Shiitake mushroom spores was established as a result of the improvement of all of his clinical symptoms, i.e., cough, weight loss, bilateral fine crackles, mild restrictive pattern of pulmonary function, and reticulo-nodular shadows on chest CT, once exposure was eliminated. Recent interest in exotic mushrooms varieties, e.g., Shiitake, in developed countries because of their possible medicinal properties might increase the potential risk of HP among mushrooms workers. Therefore, healthcare professionals have to take this new potential respiratory disease into account.

  14. 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 by...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. Occupational hypersensitivity pneumonitis: an EAACI position paper.

    PubMed

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

    2016-06-01

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

  20. Hypersensitivity pneumonitis associated with home ultrasonic humidifiers.

    PubMed

    Suda, T; Sato, A; Ida, M; Gemma, H; Hayakawa, H; Chida, K

    1995-03-01

    We describe five patients with hypersensitivity pneumonitis (HP) that was related to using home ultrasonic humidifiers. All patients had micronodular infiltrates on their chest radiograph, and their lung biopsy specimens revealed alveolitis with or without epithelioid cell granulomas. Challenge tests were performed on two patients with the humidifier water and three patients using the humidifier. All patients tested exhibited a positive response. Tests for precipitating antibodies against an extract of the humidifier water gave strongly positive reactions in all patients tested. Precipitins to Cephalosporium acremonium and Candida albicans were also present in all cases, whereas precipitins to thermophilic actinomycetes were not detected. Although cultures of the water grew a variety of fungal and bacterial organisms, thermophilic actinomycetes could not be detected. These findings suggest that thermophilic organisms may not be the causative antigens of HP associated with ultrasonic humidifiers. All five patients had an increase in the bronchoalveolar lavage (BAL) lymphocytes that were predominantly CD4+ lymphocytes. The T helper cell count (CD4) to suppressor T cell count (CD8) ratio was significantly higher than that observed in summer-type HP, and lower than that observed in bird fancier's lung, indicating that the phenotypes of the BAL lymphocytes may vary with the type of HP.

  1. 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.

  2. [Pathogenesis and treatment of hypersensitivity pneumonitis].

    PubMed

    Ando, M

    2000-01-01

    Hypersensitivity pneumonitis (HP) is a granulomatous interstitial lung disease resulting from an immunologic reaction to the repeated inhalation of organic dusts and active chemicals. There are 50 or more groups of HP, but the prevalence varies from country to country, and even within a country, depending on a variety of occupational or environmental inhalants. In Western coutries farmer's lung, bird fancier's disease, humidifier lung, and air-conditioner disease are common, but in Japan summer-type HP is the most prevalent group. Summer-type HP is a house-related illnes induced by Trichosporon asahii and Trichosporon mucoides which contaminate the patients' home environments in hot and humid conditions. The polysaccharide antigen contains mannan backbone attached with short side chains consi-sting of mannose, xylose, and glucuronic acid residues. Both immune complex-mediated and T cell-mediated immune responses to the yeast are involved in the induction and development of the disease. Host factors such as HLA-DQw3 and cigarette smoking also play an important role in the develop-ment or suppression of the disease. An assay for serum anti-Trichosporon antibody by a Triko Kit is very useful for the serodiagnosis, and sanitization by cleaning, disinfecting, and removing from the colonizing location of Trichosporon prevents recurrence of the disease. Summer-type HP induced by Trichosporon is a new type of HP. It can be found in other countries including most Western countries, because Trichosporon asahii and Trichosporon mucoides distribute in the temperate and subtropical areas of the world.

  3. An animal model of hypersensitivity pneumonitis in the rabbit.

    PubMed Central

    Moore, V L; Hensley, G T; Fink, J N

    1975-01-01

    This study was devised to produce an animal model of hypersensitivity pneumonitis in order to study both the induction and the elicitation of the disease. Rabbits exposed by aerosol to large quantities of pigeon antigens developed a humoral, but not cellular, immunologic response. Moreover, their lungs were essentially normal histologically. A single i.v. injection of killed BCG in oil permitted the induction of pulmonary cell-medid hypersensitivity to the inhaled antigen, as well as the development of pulmonary lesions which were more severe than that caused by the administration of BCG alone. The humoral immunologic response to the inhaled antigen was not increased after BCG injection. Since many individuals are exposed to the etiologic agents of hypersensitivity pneumonitis for extended periods without developing the disease, these findings in animals suggest that some event may occur to induce cell mediated hypersensitivity in order to initiate the disease process. In addition, we have shown that animals with normal lung histology and circulating complement-fixing antibodies undergo serum complement (CH50) depression after an aerosol challenge with the specific antigen. Animals with circulating, complement-fixing antibodies, and inflamed lungs (BCG-induced failed to undergo a complement depression subsequent to an aerosol challenge with specific antigens. These results re consistent with those seen in symptomatic and asymptomatic pigeon breeders and suggest that antigen distribution through the lung is important in the pathogenesis of hypersensitivity pneumonitis. Images PMID:1099122

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

    SciTech Connect

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

    1992-03-01

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

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

    PubMed

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

    2015-01-01

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

  6. 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.

  7. 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.

  8. Serum YKL-40 as predictor of outcome in hypersensitivity pneumonitis.

    PubMed

    Long, Xiaoping; He, Xuan; Ohshimo, Shinichiro; Griese, Matthias; Sarria, Rafael; Guzman, Josune; Costabel, Ulrich; Bonella, Francesco

    2017-02-01

    YKL-40, a chitinase-like protein mainly secreted by macrophages, neutrophils and epithelial cells, is increased in patients with idiopathic interstitial pneumonia and sarcoidosis. We aimed to investigate the role of YKL-40 as a biomarker in hypersensitivity pneumonitis (HP).72 HP patients, 100 interstitial lung disease (ILD) controls and 60 healthy controls were studied. YKL-40 was measured by ELISA in serum and bronchoalveolar lavage fluid (BALF) at baseline and follow-up. The relationship between YKL-40 levels, clinical variables and disease outcome was evaluated.Baseline serum YKL-40 levels were significantly higher in HP patients than in healthy controls (p<0.001), but lower than in patients with other ILDs. Baseline BALF YKL-40 levels in HP patients were the highest among ILD patients. In HP patients, serum YKL-40 correlated with the diffusing capacity of the lung for carbon monoxide at baseline (p<0.01) and over time (p<0.001). HP patients whose disease progressed or who died had higher baseline YKL-40 levels than those who remained stable and survived (p<0.001). At a cut-off of 119 ng·mL(-1), the baseline serum YKL-40 level predicted disease progression (hazard ratio 6.567; p<0.001), and at a cut-off of 150 ng·mL(-1) was associated with mortality (hazard ratio 9.989; p<0.001).Serum YKL-40 may be a useful prognostic biomarker in HP patients.

  9. 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.

  10. Hot tub lung mimicking classic acute and chronic hypersensitivity pneumonitis: Two case reports

    PubMed Central

    Verma, Geetika; Jamieson, Frances; Chedore, Pamela; Hwang, David; Boerner, Scott; Geddie, William R; Chapman, Kenneth R; Marras, Theodore K

    2007-01-01

    Pulmonary disease in otherwise healthy patients can occur by secondary exposure to nontuberculous mycobacteria from hot tubs. The pathology of hot tub lung may be related to an infection, a hypersensitivity reaction or both. Previous reports of hot tub lung have highlighted distinct pathological features that have distinguished this entity from classic hypersensitivity pneumonitis. Two cases of hot tub lung in Ontario, which presented at very different time points in their disease course, are reported; one patient presented more fulminantly with a clinical picture resembling subacute hypersensitivity pneumonitis, and the other presented with chronic disease. Both cases exhibited clinical, radiological and pathological findings closely mimicking classic subacute and chronic hypersensitivity pneumonitis. PMID:17885696

  11. Hypersensitivity pneumonitis induced by Penicillium expansum in a home environment.

    PubMed

    Park, H S; Jung, K S; Kim, S O; Kim, S J

    1994-04-01

    An episode of fever, cough, shortness of breath and leucocytosis developed in a 31-year-old atopic housewife from mould exposure in her home environment is evaluated. A chest radiograph revealed diffuse tiny nodular infiltrations in both whole lung fields. Spirometry revealed a severe restrictive type of ventilation impairment. Bronchoalveolar lavage (BAL) showed an increased lymphocyte count with reversed CD4+/CD8+ ratio and transbronchial lung biopsy showed markedly increased lymphocytic infiltration in alveolar septa. Fungal cultures in the air of her home were positive for Penicillium expansum and other fungi. Double immunodiffusion test with the patient's serum showed two precipitin bands to P. expansum antigens. Her symptoms, abnormal findings of radiograph, and spirometric abnormalities disappeared after 2 months' avoidance. The serum precipitin disappeared after 1 month's avoidance. This study indicates that the patient had hypersensitivity pneumonitis (HP) on exposure to P. expansum in her home environment.

  12. Hypersensitivity pneumonitis among wind musicians - an overlooked disease?

    PubMed

    Møller, Janne; Hyldgaard, Charlotte; Kronborg-White, Sissel Brix; Rasmussen, Finn; Bendstrup, Elisabeth

    2017-01-01

    Hypersensitivity pneumonitis (HP) is a complex pulmonary disorder mediated by the immune system and caused by various inhaled antigens against which the subject has previously been sensitized. In about 50% of the cases, the antigen is not identified. Identification and removal of the eliciting antigen is important for the prognosis. We report two cases of HP caused by molds and atypical mycobacteria isolated from wind instruments. We present the first case of HP caused by bassoon playing and another case of HP caused by molds in a trombone. HP caused by fungi and bacteria in wind instruments may be much more common than previously thought. HP caused by fungi and bacteria in wind instruments is probably underdiagnosed; this calls for more clinical attention when HP is suspected.

  13. 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.

  14. 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

  15. Quantifying serum antibody in bird fanciers' hypersensitivity pneumonitis

    PubMed Central

    McSharry, Charles; Dye, George M; Ismail, Tengku; Anderson, Kenneth; Spiers, Elizabeth M; Boyd, Gavin

    2006-01-01

    Background Detecting serum antibody against inhaled antigens is an important diagnostic adjunct for hypersensitivity pneumonitis (HP). We sought to validate a quantitative fluorimetric assay testing serum from bird fanciers. Methods Antibody activity was assessed in bird fanciers and control subjects using various avian antigens and serological methods, and the titer was compared with symptoms of HP. Results IgG antibody against pigeon serum antigens, quantified by fluorimetry, provided a good discriminator of disease. Levels below 10 mg/L were insignificant, and increasing titers were associated with disease. The assay was unaffected by total IgG, autoantibodies and antibody to dietary hen's egg antigens. Antigens from pigeon serum seem sufficient to recognize immune sensitivity to most common pet avian species. Decreasing antibody titers confirmed antigen avoidance. Conclusion Increasing antibody titer reflected the likelihood of HP, and decreasing titers confirmed antigen avoidance. Quantifying antibody was rapid and the increased sensitivity will improve the rate of false-negative reporting and obviate the need for invasive diagnostic procedures. Automated fluorimetry provides a method for the international standardization of HP serology thereby improving quality control and improving its suitability as a diagnostic adjunct. PMID:16800875

  16. 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.

  17. 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

  18. Stachybotrys chartarum-induced hypersensitivity pneumonitis is TLR9 dependent.

    PubMed

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

    2011-12-01

    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 10(6) 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. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    Funke, M; Fellrath, J-M

    2008-08-01

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

  20. 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.

  1. Hypersensitivity pneumonitis-like reaction among workers exposed to diphenylmethane [correction to piphenylmethane] diisocyanate (MDI).

    PubMed

    Vandenplas, O; Malo, J L; Dugas, M; Cartier, A; Desjardins, A; Lévesque, J; Shaughnessy, M A; Grammer, L C

    1993-02-01

    Isocyanates are well documented as a cause of occupational asthma. A hypersensitivity pneumonitis type of reaction has also been reported but only in a few isolated cases. We investigated nine subjects who complained of respiratory and general symptoms related to workplace exposure. All the subjects had worked in a plant where a resin based on diphenylmethane diisocyanate (MDI) is used in the manufacture of woodchip boards. They underwent inhalation challenges using the MDI resin for progressively increasing periods of time on separate days. In eight subjects, exposure to subirritant amounts of MDI induced a pattern of reaction consistent with hypersensitivity pneumonitis, i.e., significant falls in both FEV1 and FVC associated with a rise in body temperature (> 38 degrees C) and an increase in blood neutrophils (> +2,500/mm3). Bronchoalveolar lavage, performed in two subjects 24 h after the end of challenge exposure, revealed an increase in lymphocytes and neutrophils. Specific immunoglobulin G (IgG) and IgE antibodies to MDI human serum albumin (HSA) conjugates were present in all subjects. We conclude that the MDI resin caused an hypersensitivity pneumonitis type of reaction in at least eight (4.7%) of the 167 potentially exposed workers employed in the plant. These findings indicate that in some workplaces, a hypersensitivity pneumonitis type of reaction may be a more frequent consequence of isocyanate exposure than is usually thought.

  2. Clues for the differential diagnosis of hypersensitivity pneumonitis as an expectant variant of diffuse parenchymal lung disease

    PubMed Central

    Kupeli, E; Karnak, D; Kayacan, O; Beder, S

    2004-01-01

    Hypersensitivity pneumonitis, also called extrinsic allergic alveolitis, a type of diffuse parenchymal lung disease (DPLD), is an immunologically mediated pulmonary disease induced by inhalation of various antigens. As data on the frequency of hypersensitivity pneumonitis are lacking in Turkey, a retrospective analyses was performed in 43 patients with DPLD, followed up over seven years. The objective was to discover cases fulfilling the diagnostic criteria for hypersensitivity pneumonitis, to determine the frequency and/or the new characteristics of the disease, and to pick up clues for differentiating it from other DPLDs. The four subjects with hypersensitivity pneumonitis (9%) who lived in an urban area were studied in detail. The most common symptoms were dry cough and dyspnoea. According to the symptom duration, clinical features, radiological and pathological findings, three were diagnosed with chronic and one with subacute hypersensitivity pneumonitis. Patients with hypersensitivity pneumonitis and those with DPLD were compared by means of age, sex, smoking status, symptom duration, haematology, erythrocyte sedimentation rate, peripheral cell count, spirometric parameters, blood gases, and diffusion capacity. No statistically significant difference was detected in these parameters except for forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). In conclusion, patients with a history of antigen exposure, with mild symptoms such as dry cough and dyspnoea, and who have diffuse interstitial lung involvement on radiology should be carefully evaluated for hypersensitivity pneumonitis. Moreover, among other DPLDs, stable FEV1 or FVC values may be the clues for establishing the diagnosis of hypersensitivity pneumonitis. However, further studies are needed in larger series of patients. PMID:15192166

  3. 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

  4. Hypersensitivity pneumonitis due to occupational inhalation of fungi-contaminated corn dust.

    PubMed

    Moreno-Ancillol, A; Domínguez-Noche, C; Gil-Adrados, A C; Cosmes, P M

    2004-01-01

    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 dust of the stored maize corn has been reported as cause of respiratory symptoms. During the storage process, maize corn dust can be contaminated by moulds and thermophilic actinomycetes, which have not been described until now as the causing antigens of these symptoms. We present a case of occupational hypersensitivity pneumonitis in an agricultural worker who cultured and stored maize corn. Clinical findings, precipitating antibodies, and evolution after having removed him from his work, confirmed the diagnosis. In our case, Aspergillus species contaminating the maize corn dust are probably the antigens that caused the disease.

  5. Mycobacterium sp. as a possible cause of hypersensitivity pneumonitis in machine workers.

    PubMed

    Shelton, B G; Flanders, W D; Morris, G K

    1999-01-01

    Hypersensitivity pneumonitis (HP) in workers exposed to metal removal fluids (MRFs) is increasing. This study supports the hypothesis that aerosolized mycobacteria colonizing the MRFs likely cause the disease. Three case studies of HP outbreaks among metal workers showed potentially high exposures to a rare and newly proposed Mycobacterium species. Retrospective review of samples submitted to our laboratory showed an association between presence of mycobacteria and HP.

  6. [Actualities in extrinsic allergic alveolities or hypersensitivity pneumonitis].

    PubMed

    Ndiaye, M; Soumah, M; Sow, M L

    2007-01-01

    Significant advances have been noticed in the pathogenesis and the diagnosis of extrinsic allergic alveolitis during the last few years. Indeed the immune mechanism and the enabling conditions have been more precisely defined, the clinical stages and the diagnosis criterias clearly defined, new antigens incriminated and some etiological agents have been reclassified. The present pathogenic explanation insists on the type IV hypersensitivity reaction with sensitization of T lymphocytes, activation macrophages, the formation of IgG type antibodies and immune complexes, activation of complement and secretion of cytokines. The involvement of certain HLA classes (HLA2, DR3, DRB1, DQB1), interaction of genetics and environments factors, the role of infections agents and smoking have been demonstrated in several studies. The development of news clinical and biological diagnosis criteria have led the discovery of new extrinsic allergic alveolitis in the work places, a better knowledge of the prognostic elements and an appropriate adaptation of prevention measures.

  7. Pneumonitis

    MedlinePlus

    ... such as "farmer's lung" or "hot tub lung." Birds. Exposure to feathers or bird excrement is a common cause of pneumonitis. Radiation ... be inhaled during harvests of grain and hay. Bird handling. Poultry workers and people who breed or ...

  8. Pneumonitis

    MedlinePlus

    ... such as "farmer's lung" or "hot tub lung." Birds. Exposure to feathers or bird excrement is a common cause of pneumonitis. Radiation ... be inhaled during harvests of grain and hay. Bird handling. Poultry workers and people who breed or ...

  9. Interferon-gamma is necessary for the expression of hypersensitivity pneumonitis.

    PubMed Central

    Gudmundsson, G; Hunninghake, G W

    1997-01-01

    Farmers lung disease is a common form of hypersensitivity pneumonitis (HP) and is characterized by inflammation and granuloma formation in the lung. Interferon-gamma is important for the expression of granulomatous diseases caused by infectious agents; however, the role this mediator in regulating expression of the granulomatous response to inhaled antigen is not known. To evaluate this, we compared the response to inhaled antigen of mice that do not express the gene coding for interferon-gamma (GKO) with that of their normal littermates (WT). GKO and WT mice on a BALB/c background were exposed to 150 microg of the thermophilic bacteria Saccharopolyspora rectivirgula or saline alone, for three consecutive days a week, for 3 wk. After exposure to antigen, WT mice developed a marked granulomatous inflammation associated with an increase in lung weight and numbers of cells in bronchoalveolar lavage fluid (BAL). Although GKO mice also exhibited an increase in lung weight and numbers of cells in BAL fluid, they developed minimal inflammation and no granulomas after a similar exposure to antigen. To further evaluate if the lack of a response to antigen in GKO mice was due to lack of IFN-gamma, we replaced this mediator via intraperitoneal injections. When given replacement IFN-gamma, the GKO mice developed granulomatous inflammation in the lung. These studies show that IFN-gamma is essential for the expression of hypersensitivity pneumonitis. PMID:9153280

  10. 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

  11. 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.

  12. Nontuberculous mycobacterial hypersensitivity pneumonitis related to a home shower: treatment and secondary prevention

    PubMed Central

    Hankwitz, Paul E.; Cervia, Joseph Steven; Thomas, Charles F.; Fink, Jordan N; Marras, Ted; Tomic, Rade

    2011-01-01

    A 57-year-old physician with increasing dyspnoea and hypoxaemia had a high-resolution CT scan of the chest, which disclosed diffuse pulmonary ground glass opacities, more pronounced in the upper lobes with minimal mediastinal lymphadenopathy. Transbronchial biopsy of the right middle and lower lobes was performed, demonstrating varying degrees of well circumscribed organising granulomatous pneumonitis thought to be most consistent with hypersensitivity to nontuberculous mycobacteria. Cultures of water obtained from the patient’s home shower were positive for Mycobacterium avium complex. The patient began substituting baths for showers, experiencing some gradual improvement of his symptoms. Subsequently, he installed point-of-use 0.2 micron membrane filters on his shower, and resumed regular showering after installation with continued symptomatic improvement. CT scans at 3 and 18 months revealed improvement and resolution, respectively. Four years later, he continues to shower in filtered home shower water and remains clinically well. PMID:22689847

  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. [Two cases of hypersensitivity pneumonitis due to contamination of an ultrasonic humidifier].

    PubMed

    Gemma, H; Sato, A; Chida, K; Okano, A; Iwata, M; Yasuda, K; Taniguchi, M; Yamazaki, A; Tatsuta, Y; Nishimura, K

    1991-06-01

    Two cases of hypersensitivity pneumonitis due to contamination of ultrasonic-humidifier were reported. The first case, a 64-year-old man, developed fever and dyspnea on exertion in January 1986. He was hospitalized for 18 days and received antibiotics for presumptive bacterial pneumonia. Half a day after discharge, those symptoms recurred. On readmission, fine crackles were heard at the left lung base, and chest X-ray film showed ground glass shadows all over the lung fields. Bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) were performed on the next day after readmission. TBLB specimen revealed lymphocyte alveolitis, granulomatous tissue and infiltration of polymorphonuclear neutrophils (PMN) in alveoli. Differential cell count of the BAL fluid showed not only lymphocytosis (38.2%) but also increased PMNs (44.2%). In the second BAL performed 18 days later, the value of PMNs demonstrated a dramatic decrease. Environmental challenge tests revealed that his hypersensitivity pneumonitis was caused by an ultrasonic humidifier in his bed room. Immunological examinations showed positive Arthus type skin reaction and serum precipitin against Aspergillus fumigatus. Inhalation challenge with A. fumigatus produced cough and dyspnea with a decrease of 10 Torr in PaO2. These data suggest that A. fumigatus may be the causative antigen in this case. The second case, a 64-year-old man who had used ultrasonic humidifier in his living room, was admitted for 8 weeks with an illness characterized by cough, low fever and general malaise on 22 January 1987. Examination revealed fine crackles on both lung bases. Chest X-ray film demonstrated diffuse nodular shadows. The TBLB specimen showed lymphocytic alveolitis and bronchiolitis.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Hypersensitivity pneumonitis due to metal working fluids: Sporadic or under reported?

    PubMed

    Gupta, Amit; Rosenman, Kenneth D

    2006-06-01

    Occupational exposure to metal working fluids (MWF) is common with over 1.2 million workers in the United States involved in machine finishing, machine tooling, and other metalworking operations. MWF is a known cause of hypersensitivity pneumonitis (HP). Recent reports of outbreaks of hypersensitivity HP secondary to exposure to MWF are reported. Cases were identified through the Occupational Disease surveillance system in the State of Michigan and from referrals for evaluation to the Division of Occupational and Environmental Medicine at Michigan State University (MSU). Each patient underwent a clinical examination including an occupational history, lung function studies, radiographic imaging, and in some cases lung biopsies. Following the diagnosis of definite HP, an industrial hygiene investigation was carried out, which included a plant walk-through, and review of the "Injury and Illness" log. Air monitoring and microbial sampling results were reviewed. As part of Michigan's mandatory surveillance system for occupational illnesses, seven cases of suspected HP were identified in 2003-2004 from three facilities manufacturing automobile parts in Michigan. Each plant used semi-synthetic MWFs, and conducted a MWF management program including biocide additions. Two facilities had recently changed the MWF before the cases arose. Growth of mycobacteria was found in these two MWFs. Breathing zone samples for particulates of two employees in plant A (two cases) ranged from 0.48 to 0.56 mg/m3. In plant B (four cases), two employees' sampling results ranged from 0.10 to 0.14 mg/m3. No air sampling data were available from plant C. Hypersensitivity pneumonitis due to exposure to MWFs is under-recognized by health care providers, and current surveillance systems are inadequate to provide a true estimate of its occurrence. HP arose from environments with exposures well below the Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for MWF, and

  16. [Three cases of hypersensitivity pneumonitis caused by inhalation of spores of Pholiota nameko and the background of the disease].

    PubMed

    Konishi, K; Mouri, T; Kojima, Y; Chida, E; Sugawara, K; Abe, K; Bando, T; Ishii, M; Tamura, M

    1994-07-01

    Here we report a new type of hypersensitivity pneumonitis caused by inhalation of spores of Pholiota nameko. P. nameko is a kind of mushroom which is of Japanese delicacy. Among people who are working in nameko cultivation, we found three patients suffering from hypersensitivity pneumonitis, and identified that it was caused by inhalation of spores of P. nameko. Every patient was engaged in indoor nameko cultivation inside a building equipped with a air and moisture conditioning system for two to ten years. In the indoor environment, it was thought that they were exposed to and inhaled a high density of nameko spores. Among 15 healthy indoor nameko growers, we found 6 who had precipitating antibody against extracts from nameko spores; however, there were no antibody positive people in 17 outdoor nameko growers. As seen in dairy farmers, it was clarified that there is a percentage of precipitin positive nameko growers who are asymptomatic. This is concrete evidence that changes of mushroom cultivation style can induce a new type of hypersensitivity pneumonitis. These findings were considered to be an important experience from the view points of environmental pulmonary diseases and industrial medicine.

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

    PubMed

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

    2005-08-01

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

  18. 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

  19. 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

  20. A familial history of pulmonary fibrosis in patients with chronic hypersensitivity pneumonitis.

    PubMed

    Okamoto, Tsukasa; Miyazaki, Yasunari; Tomita, Makoto; Tamaoka, Meiyo; Inase, Naohiko

    2013-01-01

    Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease induced by the inhalation of a variety of antigens. Patients with chronic HP often have a family history of pulmonary fibrosis. This strongly suggests that both genetic and environmental factors play an important role in the pathogenesis of chronic HP. We aimed to investigate the epidemiology and clinical features of chronic HP patients with a family history of pulmonary fibrosis. We retrospectively reviewed the clinical information of 114 cases diagnosed with chronic HP with insidious onset between 1992 and 2009. Twenty cases (17.5%) were identified as having a family history of pulmonary fibrosis. All of these patients had lived apart from their afflicted relatives for at least several decades. The familial cases were younger than the nonfamilial cases at onset (57.5 ± 9.6 vs. 64.0 ± 7.0 years old, p = 0.008). The predicted vital capacity percentage and partial pressure of oxygen in arterial blood gas were significantly higher in the familial cases. There were no differences between the 2 groups in gender, smoking history, bronchoalveolar lavage fluid profile, radiologic findings or other clinical features. We found a familial clustering in patients with chronic HP. Various factors including genetic susceptibility to pulmonary fibrosis and environmental factors may contribute to the development of familial chronic HP. Copyright © 2012 S. Karger AG, Basel.

  1. Histological variability and consequences in chronic bird-related hypersensitivity pneumonitis.

    PubMed

    Ochi, Junichi; Ohtani, Yoshio; Takemura, Tamiko; Akashi, Takumi; Tateishi, Tomoya; Miyazaki, Yasunari; Inase, Naohiko; Yoshizawa, Yasuyuki

    2017-10-01

    Lobar and temporal histological variability in chronic bird-related hypersensitivity pneumonitis (BRHP) has not been clearly elucidated. This study was designed to evaluate the spatio-temporal histopathological variability in chronic BRHP. Fifty-two patients with chronic BRHP who underwent a surgical lung biopsy (SLB) between 1992 and 2008 were evaluated. The histopathological characteristics of the lung biopsy specimens were classified by the 2002 American Thoracic Society/European Respiratory Society (ATS/ERS) consensus classification of idiopathic interstitial pneumonias (IIPs). Autopsy specimens from seven patients were also evaluated to examine the serial changes from SLB to autopsy. In a study of lobar histological variability based on the findings of SLB, 7 patients were diagnosed with cellular nonspecific interstitial pneumonia (NSIP) pattern, 16 with fibrotic NSIP pattern, 20 with fibrotic NSIP pattern and usual interstitial pneumonia (UIP) (discordant UIP) pattern and 9 with UIP (concordant UIP) pattern. In a study of sequential changes, specimens of SLBs with fibrotic NSIP pattern changed to a bronchiolocentric interstitial pneumonia (BIP) pattern or UIP pattern. Interlobar and intralobar histological variability is present in chronic BRHP. In several patients with chronic BRHP, a fibrotic NSIP pattern may be an early lesion that progresses to a UIP pattern. © 2017 Asian Pacific Society of Respirology.

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

    PubMed Central

    2013-01-01

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

  3. Automated computer-based CT stratification as a predictor of outcome in hypersensitivity pneumonitis.

    PubMed

    Jacob, Joseph; Bartholmai, B J; Rajagopalan, S; Karwoski, R; Mak, S M; Mok, W; Della Casa, G; Sugino, K; Walsh, S L F; Wells, A U; Hansell, D M

    2017-09-01

    Hypersensitivity pneumonitis (HP) has a variable clinical course. Modelling of quantitative CALIPER-derived CT data can identify distinct disease phenotypes. Mortality prediction using CALIPER analysis was compared to the interstitial lung disease gender, age, physiology (ILD-GAP) outcome model. CALIPER CT analysis of parenchymal patterns in 98 consecutive HP patients was compared to visual CT scoring by two radiologists. Functional indices including forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLco) in univariate and multivariate Cox mortality models. Automated stratification of CALIPER scores was evaluated against outcome models. Univariate predictors of mortality included visual and CALIPER CT fibrotic patterns, and all functional indices. Multivariate analyses identified only two independent predictors of mortality: CALIPER reticular pattern (p = 0.001) and DLco (p < 0.0001). Automated stratification distinguished three distinct HP groups (log-rank test p < 0.0001). Substitution of automated stratified groups for FVC and DLco in the ILD-GAP model demonstrated no loss of model strength (C-Index = 0.73 for both models). Model strength improved when automated stratified groups were combined with the ILD-GAP model (C-Index = 0.77). CALIPER-derived variables are the strongest CT predictors of mortality in HP. Automated CT stratification is equivalent to functional indices in the ILD-GAP model for predicting outcome in HP. • Computer CT analysis better predicts mortality than visual CT analysis in HP. • Quantitative CT analysis is equivalent to functional indices for prognostication in HP. • Prognostication using the ILD-GAP model improves when combined with quantitative CT analysis.

  4. Use of Mycophenolate Mofetil or Azathioprine for the Management of Chronic Hypersensitivity Pneumonitis.

    PubMed

    Morisset, Julie; Johannson, Kerri A; Vittinghoff, Eric; Aravena, Carlos; Elicker, Brett M; Jones, Kirk D; Fell, Charlene D; Manganas, Helene; Dubé, Bruno-Pierre; Wolters, Paul J; Collard, Harold R; Ryerson, Christopher J; Ley, Brett

    2017-03-01

    The treatment of chronic hypersensitivity pneumonitis (cHP) often includes systemic oral corticosteroids, but the optimal pharmacologic management remains unclear. The morbidity associated with prednisone has motivated the search for alternative therapies. We aimed to determine the effect of treatment with mycophenolate mofetil (MMF) or azathioprine (AZA) on lung function in patients with cHP. Patients with cHP treated with either MMF or AZA were retrospectively identified from four interstitial lung disease centers. Change in lung function before and after treatment initiation was analyzed using linear mixed-effects modeling (LMM), adjusting for age, sex, smoking history, and prednisone use. Seventy patients were included: 51 were treated with MMF and 19 with AZA. Median follow-up after treatment initiation was 11 months. Prior to treatment initiation, FVC and diffusion capacity of the lung for carbon monoxide (Dlco) % predicted were declining at a mean rate of 0.12% (P < .001) and 0.10% (P < .001) per month, respectively. Treatment with either MMF or AZA was not associated with improved FVC (0.5% at 1 year; P = .46) but was associated with a statistically significant improvement in Dlco of 4.2% (P < .001) after 1 year of treatment. Results were similar in the subgroup of patients treated with MMF for 1 year; the FVC increased nonsignificantly by 1.3% (P = .103) and Dlco increased by 3.9% (P < .001). Treatment with MMF or AZA is associated with improvements in Dlco in patients with cHP. Prospective randomized trials are needed to validate their effectiveness for cHP. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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

    SciTech Connect

    Calhoun, W.J. )

    1991-06-01

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

  6. Toll-like receptor 6 drives interleukin-17A expression during experimental hypersensitivity pneumonitis

    PubMed Central

    Fong, Daniel J; Hogaboam, Cory M; Matsuno, Yosuke; Akira, Shizuo; Uematsu, Satoshi; Joshi, Amrita D

    2010-01-01

    Hypersensitivity pneumonitis (HP) is a T-cell-driven disease that is histologically characterized by diffuse mononuclear cell infiltrates and loosely formed granulomas in the lungs. We have previously reported that interleukin-17A (IL-17A) contributes to the development of experimental HP, and that the pattern recognition receptor Toll-like receptor 6 (TLR6) might be a factor in the initiation of this response. Using a well-established murine model of Saccharopolyspora rectivirgula-induced HP, we investigated the role of TLR6 in the immunopathogenesis of this disease. In the absence of TLR6 signalling, mice that received multiple challenges with S. rectivirgula-antigen (SR-Ag) had significantly less lung inflammation compared with C57BL/6 mice (wild-type; WT) similarly challenged with SR-Ag. Flow cytometric analysis of whole lung samples from SR-Ag-challenged mice showed that TLR6−/− mice had a decreased CD4+ : CD8+ T-cell ratio compared with WT mice. Cytokine analysis at various days after the final SR-Ag challenge revealed that whole lungs from TLR6−/− mice contained significantly less IL-17A than lungs from WT mice with HP. The IL-17A-driving cytokines IL-21 and IL-23 were also expressed at lower levels in SR-Ag-challenged TLR6−/− mice, when compared with SR-Ag-challenged WT mice. Other pro-inflammatory cytokines, namely interferon-γ and RANTES, were also found to be regulated by TLR6 signalling. Anti-TLR6 neutralizing antibody treatment of dispersed lung cells significantly impaired SR-Ag-induced IL-17A and IL-6 generation. Together, these results indicate that TLR6 plays a pivotal role in the development and severity of HP via its role in IL-17A production. PMID:20070409

  7. Immunoglobulin Free Light Chains Are Increased in Hypersensitivity Pneumonitis and Idiopathic Pulmonary Fibrosis

    PubMed Central

    Groot Kormelink, Tom; Pardo, Annie; Knipping, Karen; Buendía-Roldán, Ivette; García-de-Alba, Carolina; Blokhuis, Bart R.; Selman, Moises; Redegeld, Frank A.

    2011-01-01

    Background Idiopathic pulmonary fibrosis (IPF), a devastating lung disorder of unknown aetiology, and chronic hypersensitivity pneumonitis (HP), a disease provoked by an immunopathologic reaction to inhaled antigens, are two common interstitial lung diseases with uncertain pathogenic mechanisms. Previously, we have shown in other upper and lower airway diseases that immunoglobulin free light chains (FLCs) are increased and may be involved in initiating a local inflammation. In this study we explored if such a mechanism may also apply to HP and IPF. Methods In this study we examined the presence of FLC in serum and BAL fluid from 21 IPF and 22 HP patients and controls. IgG, IgE and tryptase concentrations were measured in BAL fluid only. The presence of FLCs, plasma cells, B cells and mast cells in lung tissue of 3 HP and 3 IPF patients and 1 control was analyzed using immunohistochemistry. Results FLC concentrations in serum and BAL fluid were increased in IPF and HP patients as compared to control subjects. IgG concentrations were only increased in HP patients, whereas IgE concentrations were comparable to controls in both patient groups. FLC-positive cells, B cells, plasma cells, and large numbers of activated mast cells were all detected in the lungs of HP and IPF patients, not in control lung. Conclusion These results show that FLC concentrations are increased in serum and BAL fluid of IPF and HP patients and that FLCs are present within affected lung tissue. This suggests that FLCs may be involved in mediating pathology in both diseases. PMID:21980441

  8. Chronic hypersensitivity pneumonitis: identification of key prognostic determinants using automated CT analysis.

    PubMed

    Jacob, Joseph; Bartholmai, Brian J; Egashira, Ryoko; Brun, Anne Laure; Rajagopalan, Srinivasan; Karwoski, Ronald; Kokosi, Maria; Hansell, David M; Wells, Athol U

    2017-05-04

    Chronic hypersensitivity pneumonitis (CHP) has a variable disease course. Computer analysis of CT features was used to identify a subset of CHP patients with an outcome similar to patients with idiopathic pulmonary fibrosis (IPF). Consecutive patients with a multi-disciplinary team diagnosis of CHP (n = 116) had pulmonary function tests (FEV1, FVC, DLco, Kco, and a composite physiologic index [CPI]) and CT variables predictive of mortality evaluated by analysing visual and computer-based (CALIPER) parenchymal features: total interstitial lung disease (ILD) extent, honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume (PVV), emphysema, and traction bronchiectasis. Mean survival was compared between both CHP and IPF patients (n = 185). In CHP, visual/CALIPER measures of reticular pattern, honeycombing, visual traction bronchiectasis, and CALIPER ILD extent were predictive of mortality (p < 0 · 05) on univariate analysis. PVV was strongly predictive of mortality on univariate (p < 0 · 0001) and multivariate analysis independent of age, gender and disease severity (represented by the CPI [p < 0 · 01]). CHP patients with a PVV threshold >6 · 5% of the lung had a mean survival (35 · 3 ± 6 · 1 months; n = 20/116 [17%]) and rate of disease progression that closely matched IPF patients (38 · 4 ± 2 · 2 months; n = 185). Pulmonary vessel volume can identify CHP patients at risk of aggressive disease and a poor IPF-like prognosis.

  9. 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.

  10. Fibrocytes contribute to inflammation and fibrosis in chronic hypersensitivity pneumonitis through paracrine effects.

    PubMed

    García de Alba, Carolina; Buendia-Roldán, Ivette; Salgado, Alfonso; Becerril, Carina; Ramírez, Remedios; González, Yolanda; Checa, Marco; Navarro, Carmen; Ruiz, Victor; Pardo, Annie; Selman, Moisés

    2015-02-15

    Hypersensitivity pneumonitis (HP) represents a lung inflammation provoked by exposure to a variety of antigens. Chronic HP may evolve to lung fibrosis. Bone marrow-derived fibrocytes migrate to injured tissues and contribute to fibrogenesis, but their role in HP is unknown. To assess the possible participation of fibrocytes in chronic HP. CD45(+)/CXCR4(+)/Col-I(+) circulating fibrocytes were evaluated by flow cytometry, and the presence of fibrocytes in HP and normal lungs by confocal microscopy. The concentration of CXCL12 in plasma and bronchoalveolar lavage fluids was quantified by ELISA. The effect of fibrocytes on lung fibroblasts and T lymphocytes was examined in co-cultures. The percentage of circulating fibrocytes was significantly increased in patients with HP compared with healthy individuals (5.3 ± 3.4% vs. 0.8 ± 0.7%; P = 0.00004). Numerous fibrocytes were found infiltrating the HP lungs near fibroblasts and lymphocytes. Plasma CXCL12 concentration was significantly increased in patients with HP (2,303.3 ± 813.7 vs. 1,385.6 ± 318.5 pg/ml; P = 0.00003), and similar results were found in bronchoalveolar lavage fluids. The chemokine was primarily expressed by epithelial cells. In co-cultures, fibrocytes induced on lung fibroblasts a significant increase in the expression of α1 type I collagen, matrix metalloprotease-1, and platelet-derived growth factor-β. Likewise, fibrocytes induced the up-regulation of CCL2 in HP lymphocytes and fibroblasts. These findings demonstrate that high levels of fibrocytes are present in the peripheral blood of patients with chronic HP and that these cells infiltrate the HP lungs. Fibrocytes may participate in the pathogenesis of HP, amplifying the inflammatory and fibrotic response by paracrine signaling inducing the secretion of a variety of proinflammatory and profibrotic molecules.

  11. The MUC5B promoter polymorphism and telomere length in patients with chronic hypersensitivity pneumonitis: an observational cohort-control study.

    PubMed

    Ley, Brett; Newton, Chad A; Arnould, Isabel; Elicker, Brett M; Henry, Travis S; Vittinghoff, Eric; Golden, Jeffrey A; Jones, Kirk D; Batra, Kiran; Torrealba, Jose; Garcia, Christine Kim; Wolters, Paul J

    2017-08-01

    Patients with hypersensitivity pneumonitis are at risk of developing pulmonary fibrosis, which is associated with reduced survival. In families with multiple affected members, individuals might be diagnosed as having idiopathic pulmonary fibrosis (IPF) or chronic (fibrotic) hypersensitivity pneumonitis, which suggests these disorders share risk factors. We aimed to test whether the genomic risk factors associated with the development and progression of IPF are also associated with the development of fibrosis and reduced survival in people with chronic hypersensitivity pneumonitis. We did an observational study of two independent cohorts of patients with chronic hypersensitivity pneumonitis, one from the University of California San Francisco, CA, USA (UCSF), and one from the University of Texas Southwestern, TX, USA (UTSW). We measured two common single-nucleotide polymorphisms associated with IPF (MUC5B rs35705950 and TOLLIP rs5743890) and telomere length in peripheral blood leucocytes, and assessed their associations with chronic hypersensitivity pneumonitis risk, survival, and clinical, radiographic, and pathological features. We compared findings with those in patients with IPF from the UCSF and UTSW cohorts, and healthy controls from the European population of the 1000 Genomes Project Phase 3, version 1. The cohorts included 145 patients from UCSF and 72 from UTSW. The minor allele frequency (MAF) was greater for MUC5B rs35705950 in patients with chronic hypersensitivity pneumonitis than in healthy controls (24·4% in UCSF and 32·3% in UTSW vs 10·7%, both p<0·0001), but not for TOLLIP rs5743890. The MAFs were similar to those for IPF (UCSF 33·3%, p=0·09; UTSW 32·0%, p=0·95). In the combined UCSF and UTSW chronic hypersensitivity pneumonitis cohort, we saw associations between extent of radiographic fibrosis and MUC5B rs35705950 minor alleles (adjusted odds ratio [OR] 1·91, 95% CI 1·02-3·59, p=0·045) and short telomere length (adjusted OR per unit

  12. Identifying an Inciting Antigen Is Associated With Improved Survival in Patients With Chronic Hypersensitivity Pneumonitis

    PubMed Central

    Swigris, Jeffrey J.; Forssén, Anna V.; Tourin, Olga; Solomon, Joshua J.; Huie, Tristan J.; Olson, Amy L.; Brown, Kevin K.

    2013-01-01

    Background: The cornerstone of hypersensitivity pneumonitis (HP) management is having patients avoid the inciting antigen (IA). Often, despite an exhaustive search, an IA cannot be found. The objective of this study was to examine whether identifying the IA impacts survival in patients with chronic HP. Methods: We used the Kaplan-Meier method to display, and the log-rank test to compare, survival curves of patients with well-characterized chronic HP stratified on identification of an IA exposure. A Cox proportional hazards (PH) model was used to identify independent predictors in time-to-death analysis. Results: Of 142 patients, 67 (47%) had an identified IA, and 75 (53%) had an unidentified IA. Compared with survivors, patients who died (n = 80, 56%) were older, more likely to have smoked, had lower total lung capacity % predicted and FVC % predicted, had higher severity of dyspnea, were more likely to have pulmonary fibrosis, and were less likely to have an identifiable IA. In a Cox PH model, the inability to identify an IA (hazard ratio [HR], 1.76; 95% CI, 1.01-3.07), older age (HR, 1.04; 95% CI, 1.01-1.07), the presences of pulmonary fibrosis (HR, 2.43; 95% CI, 1.36-4.35), a lower FVC% (HR, 1.36; 95% CI, 1.10-1.68), and a history of smoking (HR, 2.01; 95% C1, 1.15-3.50) were independent predictors of shorter survival. After adjusting for mean age, presence of fibrosis, mean FVC%, mean diffusing capacity of the lung for carbon monoxide (%), and history of smoking, survival was longer for patients with an identified IA exposure than those with an unidentified IA exposure (median, 8.75 years vs 4.88 years; P = .047). Conclusions: Among patients with chronic HP, when adjusting for a number of potentially influential predictors, including the presence of fibrosis, the inability to identify an IA was independently associated with shortened survival. PMID:23828161

  13. Sub-acute occupational hypersensitivity pneumonitis due to low-level exposure to diisocyanates in a secretary.

    PubMed

    Schreiber, J; Knolle, J; Sennekamp, J; Schulz, K T; Hahn, J U; Hering, K G; Raulf-Heimsoth, M; Merget, R

    2008-09-01

    There is virtually no information in the literature about the exposure levels needed to induce hypersensitivity pneumonitis (HP) by diisocyanates. The present study reports a case of occupational HP due to diisocyanates after low-level exposure. A 53-yr-old female never-smoker developed progressive shortness of breath on exertion, cough, fatigue and flu-like symptoms shortly after she began work as a secretary of a car body repair shop. A diagnosis of HP was made 2 yrs later, based on a restrictive ventilatory defect, a reticulonodular and discrete ground-glass pattern on high-resolution computed tomography, lymphocytosis in bronchoalveolar lavage and specific immunoglobulin G antibodies to diisocyanate human serum albumin conjugates in the patient's serum. The diagnosis was confirmed by recovery after exposure cessation and deterioration after re-exposure. Ambient monitoring revealed air concentrations of different diisocyanate monomers below the detection limit in both the patient's work station and in front of the paint spray booths, with the exception of one measurement that showed 4,4-methylenediphenyl diisocyanate concentrations of 3 microg x m(-3) in front of one booth (corresponding to a total reactive isocyanate group concentration of 1 microg x m(-3)). The present authors conclude that concentrations of diisocyanates far below current exposure limits may induce hypersensitivity pneumonitis in susceptible subjects.

  14. 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.

  15. Pathology of Chronic Hypersensitivity Pneumonitis: What Is It? What Are the Diagnostic Criteria? Why Do We Care?

    PubMed

    Churg, Andrew; Bilawich, AnaMaria; Wright, Joanne L

    2017-05-24

    - Chronic hypersensitivity pneumonitis (CHP) has emerged from obscurity during the past 15 years and is now recognized as a very common form of fibrosing interstitial pneumonia but one that is frequently misdiagnosed both clinically and on surgical lung biopsy as usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) or fibrotic nonspecific interstitial pneumonia. - To review the pathologic features of CHP. - Clinical, pathology, and radiology literature were used. - Upper lobe-predominant fibrosis and/or air-trapping on computed tomography scan are features of CHP but not UIP/IPF; however, radiologic separation is possible in only about 50% of cases. Morphologically, CHP sometimes mimics UIP/IPF, but CHP often shows isolated foci of peribronchiolar (centrilobular) fibrosis, frequently associated with fibroblast foci, and in CHP, fibrosis may bridge from the centrilobular region to another bronchiole, an interlobular septum, or the pleura ("bridging fibrosis"). This set of findings is uncommon in UIP/IPF. In addition, CHP may produce a picture of fibrotic nonspecific interstitial pneumonia. Although giant cells/granulomas are usually present in subacute hypersensitivity pneumonitis, they are much less frequently found in CHP, and their absence does not contradict the diagnosis. This diagnostic separation is clinically important because CHP is treated differently than UIP/IPF is (immunosuppressive agents versus antifibrotic agents); further, there are some data to suggest that removing the patient from antigen exposure improves outcome, and there is evidence that patients with CHP have a much survival prognosis after lung transplantation than do patients with UIP/IPF. In most cases, accurate diagnosis of CHP requires consultation among clinicians, radiologists, and pathologists.

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

    SciTech Connect

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

    2010-09-01

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

  17. Pet Groomer's Lung: A novel occupation related hypersensitivity pneumonitis related to pyrethrin exposure in a pet groomer.

    PubMed

    Pu, Chan Yeu; Rasheed, Mohamed Rizwan Haroon Al; Sekosan, Marin; Sharma, Vibhu

    2017-01-01

    A 61-year-old man was evaluated for a 2 month history of cough and dyspnea without relevant exposures other than pyrethrin containing insecticidal sprays he used while grooming dogs almost daily. High Resolution Computed Tomography (HRCT) of the chest demonstrated a Non-Specific Interstitial Pneumonia (NSIP) pattern. Pulmonary function testing revealed an isolated mildly reduced diffusion capacity. Bronchoalveolar lavage (BAL) results confirmed the presence of foamy histiocytes, lymphocytes, and polymorphonuclear cells consistent with ongoing exposure. Open lung biopsy showed poorly formed granulomas and bronchiolitis. He was advised to avoid exposure to pyrethrin. While he declined to stop grooming dogs, on follow-up, his symptoms had improved with use of a P100 mask and better ventilation to protect himself when using the pet sprays. We conclude that sustained exposure to pyrethrin containing sprays in the pet grooming industry may be a risk factor for a novel occupation related hypersensitivity pneumonitis. ("Pet Groomer's Lung"). Am. J. Ind. Med. 60:141-145, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. [Hypersensitivity pneumonitis related to Penicillium chrysogenum and mesophilic Streptomyces: the usefulness of the Medical Indoor Environment Councelor (MIEC)].

    PubMed

    Tiotiu, A; Metz-Favre, C; Reboux, G; Kessler, R; de Blay, F

    2013-10-01

    Hypersensitivity pneumonitis (HP) occurred after organic antigens inhalation at home is rare and the diagnosis is very often difficult. We report the case of a 55-year male patient with allergic asthma since childhood, well controlled with inhaled corticosteroids, twice hospitalized for respiratory distresses. The patient presented fever (39°C), dry cough, rapidly progressive dyspnea, chest pain and crackles. Blood gas analysis found a hypoxemia of 52 mmHg, and CT-scan showed ground glass images in the upper lobes. Respiratory function tests showed severe obstructive syndrome and a decrease of diffusion test. HP was suspected because the symptoms were triggered by domestic environmental. The Medical Indoor Environment Councelor (MIEC) visited the patient's house and camper and performed air and dust samples. Moldy walnuts were found in the camper. The identification of microorganisms present in the air and on the surfaces in the camper was used for serum precipitins research by double diffusion (DD) and electrosyneresis (E) methods. From the 14 antigens tested, serological tests were considered significant for mesophilic Streptomyces (five arcs DD, six arcs E) and Penicillium chrysogenum (one arc DD, four arcs E). After removal from the camper of the objects suspected to be contaminated, the patient's symptoms regressed. This is a typical case of domestic HP to mesophilic Streptomyces and P. chrysogenum. The MIEC's intervention was useful in both diagnosis and treatment.

  19. Hypersensitivity pneumonitis in a cluster of sawmill workers: a 10-year follow-up of exposure, symptoms, and lung function

    PubMed Central

    Færden, Karl; Lund, May Brit; Aaløkken, Trond Mogens; Eduard, Wijnand; Søstrand, Per; Langård, Sverre; Kongerud, Johny

    2014-01-01

    Background: The long-term prognosis of repeated acute episodes of hypersensitivity pneumonitis (HP) is not well described. We report on a 10-year follow-up of a 10-person cluster from a Norwegian sawmill who had all experienced relapsing episodes of HP. Objectives: To evaluate the health symptoms, work-related sick-leave, and lung function of 10 workers exposed to mold in a Norwegian sawmill. Methods: Participants were evaluated at baseline and 10 years later at follow-up. A structured interview, measurement of serum IgG antibodies to Rhizopus microsporus (R. microsporus) antigens, lung function tests, high resolution computed tomography (HRCT) of the chest, and personal measurements of exposure to mold spores and dust were completed for each participant. Results: At baseline, nearly all workers reported acute episodes of HP more than twice a month. At follow-up, both the frequency and intensity of symptoms had declined. Sick-leave was reduced and gas diffusing capacity improved – paralleling the gradually reduced air levels of mold spores. Conclusions: In spite of an initially high occurrence of symptoms, long-term clinical and physiological outcome was good. With reduced exposure to mold spores, symptoms declined and lung function was restored. PMID:24999852

  20. Human Monocyte-Derived Dendritic Cells Exposed to Microorganisms Involved in Hypersensitivity Pneumonitis Induce a Th1-Polarized Immune Response

    PubMed Central

    Pallandre, Jean-René; Borg, Christophe; Loeffert, Sophie; Gbaguidi-Haore, Houssein; Millon, Laurence

    2013-01-01

    Hypersensitivity pneumonitis (HP) is an immunoallergic disease characterized by a prominent interstitial infiltrate composed predominantly of lymphocytes secreting inflammatory cytokines. Dendritic cells (DCs) are known to play a pivotal role in the lymphocytic response. However, their cross talk with microorganisms that cause HP has yet to be elucidated. This study aimed to investigate the initial interactions between human monocyte-derived DCs (MoDCs) and four microorganisms that are different in nature (Saccharopolyspora rectivirgula [actinomycetes], Mycobacterium immunogenum [mycobacteria], and Wallemia sebi and Eurotium amstelodami [filamentous fungi]) and are involved in HP. Our objectives were to determine the cross talk between MoDCs and HP-causative agents and to determine whether the resulting immune response varied according to the microbial extract tested. The phenotypic activation of MoDCs was measured by the increased expression of costimulatory molecules and levels of cytokines in supernatants. The functional activation of MoDCs was measured by the ability of MoDCs to induce lymphocytic proliferation and differentiation in a mixed lymphocytic reaction (MLR). E. amstelodami-exposed (EA) MoDCs expressed higher percentages of costimulatory molecules than did W. sebi-exposed (WS), S. rectivirgula-exposed (SR), or M. immunogenum-exposed (MI) MoDCs (P < 0.05, Wilcoxon signed-rank test). EA-MoDCs, WS-MoDCs, SR-MoDCs, and MI-MoDCs induced CD4+ T cell proliferation and a Th1-polarized immune response. The present study provides evidence that, although differences were initially observed between MoDCs exposed to filamentous fungi and MoDCs exposed to bacteria, a Th1 response was ultimately promoted by DCs regardless of the microbial extract tested. PMID:23720369

  1. 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

  2. TLR9-dependent IL-23/IL-17 is required for the generation of Stachybotrys chartarum-induced hypersensitivity pneumonitis.

    PubMed

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

    2013-01-01

    Hypersensitivity pneumonitis (HP) is an inflammatory lung disease that develops after repeated exposure to inhaled particulate Ag. Stachybotrys chartarum is a dimorphic fungus that has been implicated in a number of respiratory illnesses, including HP. In this study, we have developed a murine model of S. chartarum-induced HP that reproduces pathology observed in human HP, and we have hypothesized that TLR9-mediated IL-23 and IL-17 responses are required for the generation of granulomatous inflammation induced by inhaled S. chartarum. Mice that undergo i.p. sensitization and intratracheal challenge with 10(6) S. chartarum spores developed granulomatous inflammation with multinucleate giant cells, accompanied by increased accumulation of T cells. S. chartarum sensitization and challenge resulted in robust pulmonary expression of IL-17 and IL-23. S. chartarum-mediated granulomatous inflammation required intact IL-23 or IL-17 responses and required TLR9, because 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. Compared with S. chartarum-sensitized dendritic cells (DC) isolated from WT mice, DCs isolated from TLR9(-/-) mice had a reduced ability to produce IL-23 in responses to S. chartarum. Moreover, shRNA knockdown of IL-23 in DCs abolished IL-17 production from splenocytes in response to Ag challenge. Finally, the intratracheal reconstitution of IL-23 in TLR9(-/-) mice recapitulated the immunopathology observed in WT mice. In conclusion, our studies suggest that TLR9 is critical for the development of Th17-mediated granulomatous inflammation in the lung in response to S. chartarum.

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

    PubMed Central

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

    2015-01-01

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

  4. Protein kinase D1 is essential for the pro-inflammatory response induced by hypersensitivity pneumonitis-causing thermophilic actinomycetes Saccharopolyspora rectivirgula

    PubMed Central

    Kim, Young-In; Park, Jeoung-Eun; Brand, David D.; Fitzpatrick, Elizabeth A.; Yi, Ae-Kyung

    2010-01-01

    Hypersensitivity pneumonitis is an interstitial lung disease that results from repeated pulmonary exposure to various organic antigens, including Saccharopolyspora rectivirgula (SR, the causative agent of farmer's lung disease). Although the contributions of pro-inflammatory mediators to the disease pathogenesis are relatively well documented, the mechanism(s) involved in initiation of pro-inflammatory responses against the causative microorganisms, and the contribution of signaling molecules involved in host immune defense have not been fully elucidated. In the present study, we found that SR induces activation of protein kinase D1 (PKD1) in lung cells in vitro and in vivo. Activation of PKD1 by SR was dependent on MyD88. Inhibition of PKD by pharmacological PKD inhibitor Gö6976, and silencing of PKD1 expression by siRNA, revealed that PKD1 is indispensable for SR-mediated activation of MAPKs and NF-κB and expression of various pro-inflammatory cytokines and chemokines. In addition, compared to controls, mice pretreated with Gö6976 showed significantly suppressed alveolitis and neutrophil influx in bronchial alveolar lavage fluid and interstitial lung tissue, and substantially decreased myeloperoxidase activity in the lung after pulmonary exposure to SR. These results demonstrate that PKD1 is essential for SR-mediated pro-inflammatory immune responses and neutrophil influx in the lung. Our findings also imply the possibility that PKD1 might be one of the critical factors that play a regulatory role in development of hypersensitivity pneumonitis caused by microbial antigens, and that inhibition of PKD1 activation could be an effective way to control microbial antigen-induced hypersensitivity pneumonitis. PMID:20142359

  5. 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. Copyright © 2013. Published by Elsevier Ltd.

  6. The effect of CTLA-4Ig, a CD28/B7 antagonist, on the lung inflammation and T cell subset profile during murine hypersensitivity pneumonitis.

    PubMed

    Jiménez-Alvarez, Luis; Arreola, José Luis; Ramírez-Martínez, Gustavo; Ortiz-Quintero, Blanca; Gaxiola, Miguel; Reynoso-Robles, Rafael; Avila-Moreno, Federico; Urrea, Francisco; Pardo, Annie; Selman, Moisés; Zuñiga, Joaquín

    2011-12-01

    Hypersensitivity pneumonitis (HP) is an inflammatory lung disease characterized by an influx of activated T cells to the lung, in which the CD28/B7 costimulatory signals are essential for the T cell activation and the outcome of the inflammatory response. In this study, we investigated the effect of the CD28/B7 antagonist, CTLA-4Ig, on the lung inflammation and the T cell subset profile in experimental Saccharopolyspora recivirgula (SR)-induced HP. C57BL/6 mice were treated with SR or saline during two and three weeks and in addition of CTLA-4Ig was administrated after either the second or third week and mice were sacrificed seven days later. The extent of the lung inflammation was quantified by histopathology and the lung T cell subsets (Treg, Th17, γδT and NKT) were analyzed by flow cytometry. Mice treated with CTLA-4Ig showed a significant decrease in the extent of lung damage (p<0.05), and exhibited a decreased number of inflammatory cells in the bronchoalveolar lavage (BAL) with diminished CD4/CD8 T cell ratio. Also, a significant increase in the percentage of lung γδT (p<0.01) and NKT (p<0.05) cells was observed in two weeks SR-treated mice with the administration of CTLA-4Ig/SR. At 3 weeks, SR-treated mice showed an increased percentage of regulatory T cells but no significantly differences were found in the percentage of Th17 cells when compared with CTLA-4Ig/SR-treated mice. Our findings suggest that the treatment with CTLA-4Ig affects the HP progression and the lung T cell subset kinetics in mice.

  7. How Is Hypersensitivity Pneumonitis Treated?

    MedlinePlus

    ... treat severe chronic disease in some patients. Avoidance strategies If your doctor is able to identify the ... will recommend that you adopt the following avoidance strategies. Remove the causative substance if possible Replace workplace ...

  8. Correlation of dosimetric and clinical factors with the development of esophagitis and radiation pneumonitis in patients with limited-stage small-cell lung carcinoma.

    PubMed

    Giuliani, Meredith E; Lindsay, Patricia E; Kwan, Jennifer Y Y; Sun, Alexander; Bezjak, Andrea; Le, Lisa W; Brade, Anthony; Cho, John; Leighl, Natasha B; Shepherd, Frances A; Hope, Andrew J

    2015-05-01

    The purpose of the study was to correlate clinical and dosimetric factors with the development of esophagitis and radiation pneumonitis in patients with limited-stage small-cell lung carcinoma (LS SCLC). One hundred eighteen patients who received curative intent chemoradiotherapy for LS SCLC and had electronically archived radiation treatment plans were included. The medical charts were reviewed for clinical data. The treatment plan was reviewed for critical structure delineation and dose delivered. Treatment planning data were analyzed using Computational Environment for Radiotherapy Research (V3.3). Dosimetric parameters were correlated with the risk of toxicity using Spearman rank correlation. Radiotherapy dose was 40 Gy in 15 fractions (fx) (n = 80) and 45 Gy in 30 fractions twice per day (n = 38). The 6-month cumulative incidence of Grade ≥ 2 radiation pneumonitis was 6.5% and 7.9% for the 40 Gy/15 fx and 45 Gy/30 fx groups, respectively (P = .40). The 3-month cumulative incidence of Grade 3 esophagitis was 7.5% and 13.2% for the 40 Gy/15 fx and 45 Gy/30 fx groups, respectively (P = .31). Grade ≥ 3 pneumonitis was correlated with volume of lung receiving 20 Gy (V20) and mean lung dose. Grade ≥ 3 esophagitis was correlated with mean esophagus dose and minimum dose to the hottest 45% of the esophagus (D45). Mean lung dose and V20 were significant predictors of radiation pneumonitis in LS SCLC. Mean esophageal dose and D45 were significant predictors of esophagitis. These 2 treatment schedules have similar toxicity profiles. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. 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

  10. Correlation of Radiation Pneumonitis History Before Nivolumab with Onset of Interstitial Lung Disease and Progression-free Survival of Patients with Pre-treated Advanced Non-small Cell Lung Cancer.

    PubMed

    Tamiya, Akihiro; Tamiya, Motohiro; Nakahama, Kenji; Taniguchi, Yoshihiko; Shiroyama, Takayuki; Isa, Shun-Ichi; Inoue, Takako; Okishio, Kyoichi; Nishino, Kazumi; Kumagai, Toru; Suzuki, Hidekazu; Hirashima, Tomonori; Imamura, Fumio; Atagi, Shinji

    2017-09-01

    Nivolumab has a promising efficacy for patients with non-small-cell lung cancer (NSCLC) as second-line or later treatment, and after radiotherapy as abscopal effect. However, the effects of radiation pneumonitis history before nivolumab have not been clarified. Therefore, we retrospectively analyzed the correlation of a history of radiation pneumonitis before nivolumab with onset of interstitial lung disease (ILD) and progression-free survival (PFS) after nivolumab treatment in patients with previously treated NSCLC. A total of 201 patients treated with nivolumab were retrospectively reviewed. We collected clinical data of patients at the time of starting nivolumab and we evaluated ILD incidence and PFS in relation to patient characteristics, including radiation pneumonitis history. The median age was 68 years; 135 patients were men, 157 had a smoking history, and 153 had performance status of 0 or 1. Thirty-four patients experienced radiation pneumonitis before nivolumab, and 50 patients received radiotherapy to the chest (31 patients received curative radiotherapy). The overall median PFS was 2.8 months and the overall ILD rate was 12.4%. Higher ILD incidence was observed in the group with a history of radiation pneumonitis (26.5%) compared to the group without radiation pneumonitis (9.6%). The median PFS was 3.6 and 2.3 months, respectively. On multivariate analysis, a history of radiation pneumonitis was also significantly correlated with good PFS (p=0.023). Although increasing the risk of ILD, a history of radiation pneumonitis before nivolumab also contributes to the prolongation of PFS after nivolumab. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Correlation between Helicobacter pylori infection, IgE hypersensitivity, and allergic disease in Korean adults.

    PubMed

    Lee, Sang Pyo; Lee, Sun-Young; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sup; Moon, Hee-Won

    2015-02-01

    The correlation between allergic disease and Helicobacter pylori infection is still controversial in endemic areas. The aim of this study was to determine whether H. pylori infection is related to allergic disease and/or immunoglobulin E (IgE) hypersensitivity in Korean adults. Consecutive Korean adults who visited our center for a routine checkup were enrolled. All subjects completed a questionnaire that was designed to ascertain their medical history pertaining to physician-diagnosed allergic disease, allergy treatments, and H. pylori eradication therapy. Blood was sampled for serum anti-H. pylori IgG antibody. IgE hypersensitivity was measured using a commercially available ImmunoCAP(®) Phadiatop (Phadia AB, Uppsala, Sweden). Of the 3376 Korean adults who were enrolled, 62 did not answer to the questionnaires adequately and were thus excluded. The proportion of noninfected subjects (p < .001) and the prevalence of IgE-related allergic disease (p < .001) were both highest among those aged <40 years, while the prevalence of non-IgE-related allergic disease was highest among those aged ≥70 years (p < .001). Logistic regression analysis revealed that being younger than 40 years was significantly related to the absence of H. pylori infection (OR = 2.507, 95% CI = 1.621-3.878, p < .001). The statuses of H. pylori infection, IgE hypersensitivity, and allergic diseases differ with age group, there being a higher prevalence of IgE-related allergic disease and a lower H. pylori infection rate among young adults. The hygiene hypothesis might explain these findings in young Koreans, due to the rapid development and improvements in sanitation in Korea. © 2014 John Wiley & Sons Ltd.

  12. Alopecia in Rhesus macaques correlates with immunophenotypic alterations in dermal inflammatory infiltrates consistent with hypersensitivity etiology.

    PubMed

    Kramer, Joshua; Fahey, Michele; Santos, Rosemary; Carville, Angela; Wachtman, Lynn; Mansfield, Keith

    2010-04-01

    Although alopecia is a commonly recognized problem affecting many captive Rhesus macaque colonies, there is no consensus as to the underlying etiology or appropriate course of management. We performed skin biopsies to assess underlying pathology in alopecic Rhesus macaques and performed immunohistochemical and metachromatic staining of these biopsies to assess the cellular infiltrates. Alopecia is associated with superficial dermal perivascular mononuclear cell infiltrates and skin pathology consistent with chronic hypersensitivity dermatitis. The inflammation is primarily composed of CD4+ cells admixed with histiocytes and mast cells. Inflammation is correlated with degree of alopecia. Further analysis in different groups of macaques revealed that animals born outdoors or infected with lung mites had reduced dermal inflammatory cell infiltrates and a lower incidence of alopecia. These findings support a hypothesis that an altered housing status resulting in decreased pathogen burden in Rhesus macaque colonies may contribute to dermal immunophenotypic alterations and subsequent development of dermatitis with resultant alopecia.

  13. Alopecia in Rhesus macaques correlates with immunophenotypic alterations in dermal inflammatory infiltrates consistent with hypersensitivity etiology

    PubMed Central

    Kramer, Joshua; Fahey, Michele; Santos, Rosemary; Carville, Angela; Wachtman, Lynn; Mansfield, Keith

    2010-01-01

    Background Although alopecia is a commonly recognized problem affecting many captive Rhesus macaque colonies, there is no consensus as to the underlying etiology or appropriate course of management. Methods and Results We performed skin biopsies on a group of Rhesus macaques and demonstrate that alopecia is associated with superficial dermal perivascular mononuclear cell infiltrates and skin pathology consistent with chronic hypersensitivity dermatitis. Immunohistochemistry demonstrated that the inflammation is primarily composed of CD4+ cells admixed with histiocytes and mast cells. Inflammation is correlated with degree of alopecia. Further analysis in different groups of macaques revealed that animals born outdoors or infected with lung mites had reduced dermal inflammatory cell infiltrates and a lower incidence of alopecia. Conclusions These findings support a hypothesis that an altered housing status resulting in decreased pathogen burden in Rhesus macaque colonies may contribute to dermal immunophenotypic alterations and subsequent development of dermatitis with resultant alopecia. PMID:20102458

  14. 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

  15. Guidelines for the clinical evaluation of hypersensitivity pneumonitis. Report of the Subcommittee on Hypersensitivity Pneumonitis

    SciTech Connect

    Richerson, H.B.; Bernstein, I.L.; Fink, J.N.; Hunninghake, G.W.; Novey, H.S.; Reed, C.E.; Salvaggio, J.E.; Schuyler, M.R.; Schwartz, H.J.; Stechschulte, D.J. )

    1989-11-01

    In general, a history of exposure to moldy hay, birds, or other incriminated occupational or environmental inhalants in a patient with clinical and radiologic features consistent with HSP should lead to the demonstration of serum precipitins to the suspected antigen and an established diagnosis, confirmed by avoidance of the agent involved. Occasionally, other diagnostic procedures are required. The diagnosis is often difficult in domestic exposures, such as humidification and air conditioning systems. A careful environmental history is essential, and at times the physician must inspect the patient's environment personally. In most cases, the diagnosis is established if (1) the history and physical findings and pulmonary function tests indicate an interstitial lung disease, (2) the x-ray film is consistent, (3) there is exposure to a recognized cause, and (4) there is antibody to that antigen. In other exceptional circumstances, bronchoalveolar lavage may help. Biopsy is rarely needed. Special environmental studies and identification of new antigens require research facilities. Provocation tests are research procedures, not necessary for the diagnosis, and not needed in contested workmen's compensation adjudications.

  16. Interstitial pneumonitis induced in guinea pigs by Triatoma infestans antigens.

    PubMed

    Alonso, A; Caccuri, R L; Scavini, L M; Rodríguez, S M; Marino, G A

    1994-01-01

    Data concerning the experimental induction of hypersensitivity pneumonitis in guinea pigs with a Triatoma infestans antigen are presented. Glycoproteins obtained from the chitinous structures of T. infestans (79 kd + 11 kd) were aerosolized daily to guinea pigs during 7 weeks. The presence of specific antibodies (IgG and IgE) was detected by serological techniques; histopathological studies of the lungs showed interstitial infiltrates of macrophages and T-cells. Single non-necrotizing granulomas were seen at the seventh week of the experiment. The results from this animal model suggest that this hypersensitivity pneumonitis is a typical delayed-type reaction due to chronic contact with the heterologous glycoproteins of T. infestans.

  17. Lessons from Mycobacterium avium complex-associated pneumonitis: a case report

    PubMed Central

    Zota, Victor; Angelis, Sheryn M; Fraire, Armando E; McNamee, Ciaran; Kielbasa, Shasta; Libraty, Daniel H

    2008-01-01

    Introduction Mycobacterium avium complex (MAC) is an increasingly recognized cause of pulmonary disease in immunocompetent individuals. An acute form of MAC lung disease, MAC-associated pneumonitis, has generally been associated with the use of hot tubs. There is controversy in the literature about whether MAC-associated pneumonitis is a classic hypersensitivity pneumonitis or is a direct manifestation of mycobacterial infection. Case presentation We report the second case in the literature of MAC-associated pneumonitis not related to the use of hot tubs. The source of MAC in a 52-year-old immunocompetent patient was an intrapulmonary cyst containing numerous acid-fast bacilli. The patient developed disseminated miliary nodules throughout both lung fields. Histological examination of resected lung tissue revealed well-formed, acid-fast negative granulomas composed predominantly of CD4+ T-cells and CD68+ histiocytes. The granulomas were strongly positive for tumor necrosis factor-α, a pro-inflammatory cytokine. Conclusion The attempt to classify MAC-associated pneumonitis as either a classic hypersensitivity pneumonitis or a direct manifestation of mycobacterial infection is not particularly useful. Our case demonstrates that MAC-associated pneumonitis is characterized by a vigorous T-helper 1-like, pro-inflammatory, immune response to pulmonary mycobacterial infection. The immunopathology provides a rationale for clinical studies of anti-MAC therapy with the addition of anti-inflammatory agents (for example, corticosteroids) to hasten the resolution of infection and symptoms. PMID:18477401

  18. Lessons from Mycobacterium avium complex-associated pneumonitis: a case report.

    PubMed

    Zota, Victor; Angelis, Sheryn M; Fraire, Armando E; McNamee, Ciaran; Kielbasa, Shasta; Libraty, Daniel H

    2008-05-13

    Mycobacterium avium complex (MAC) is an increasingly recognized cause of pulmonary disease in immunocompetent individuals. An acute form of MAC lung disease, MAC-associated pneumonitis, has generally been associated with the use of hot tubs. There is controversy in the literature about whether MAC-associated pneumonitis is a classic hypersensitivity pneumonitis or is a direct manifestation of mycobacterial infection. We report the second case in the literature of MAC-associated pneumonitis not related to the use of hot tubs. The source of MAC in a 52-year-old immunocompetent patient was an intrapulmonary cyst containing numerous acid-fast bacilli. The patient developed disseminated miliary nodules throughout both lung fields. Histological examination of resected lung tissue revealed well-formed, acid-fast negative granulomas composed predominantly of CD4+ T-cells and CD68+ histiocytes. The granulomas were strongly positive for tumor necrosis factor-alpha, a pro-inflammatory cytokine. The attempt to classify MAC-associated pneumonitis as either a classic hypersensitivity pneumonitis or a direct manifestation of mycobacterial infection is not particularly useful. Our case demonstrates that MAC-associated pneumonitis is characterized by a vigorous T-helper 1-like, pro-inflammatory, immune response to pulmonary mycobacterial infection. The immunopathology provides a rationale for clinical studies of anti-MAC therapy with the addition of anti-inflammatory agents (for example, corticosteroids) to hasten the resolution of infection and symptoms.

  19. Bacterial species diversity in cigarettes linked to an investigation of severe pneumonitis in U.S. Military personnel deployed in operation iraqi freedom.

    PubMed

    Rooney, Alejandro P; Swezey, James L; Wicklow, Donald T; McAtee, Matthew J

    2005-07-01

    This report presents results from a study on the bacterial diversity of cigarette brands collected from military personnel during the U.S. Army's investigation of a series of cases of acute eosinophilic pneumonitis in military personnel deployed in Operation Iraqi Freedom. Eight species of Bacillus, including five new species, and one new species of Kurthia were isolated from the cigarettes. Some of these species have been identified elsewhere as causes of hypersensitivity pneumonitis and other respiratory syndromes. All of the isolates were facultative anaerobes, and many displayed mucoid growth under anaerobic conditions. In addition, many isolates also displayed the ability to form surface biofilms under liquid culture. Although biofilm formation and mucoid growth were not correlated, the former was found to be much more pronounced under anaerobic conditions as opposed to aerobic ones. The implications of these findings are discussed.

  20. [Chronic interstitial pneumonitis].

    PubMed

    Almeida, Rui; Reis, Guilhermina; Ferreira, Cristina; Oliveira, Ma José; Oliveira, Dulce; Fernandes, Paula; Ferreira, Paula; Frutuoso, Simão; Carreira, Luísa; Alves, Valter; Paiva, António; Guedes, Margarida

    2004-01-01

    Interstitial lung disease includes a group of chronic diseases characterized by alterations in alveolar walls and loss of functional alveolar-capillary units. These are rare diseases in children, mostly with an unknown cause and associated with a high morbidity and mortality due to insufficient therapeutic effectiveness. The authors report a case of a previously healthy 3 years old child who presented with wheezing and severe respiratory insufficiency following a respiratory infection. The investigation performed led to the diagnosis of chronic interstitial pneumonitis. Several treatments have been tried (corticosteroids, hydroxychloroquine, N-acetylcysteine) without any obvious improvement.

  1. BCG-induced pneumonitis with lymphocytic pleurisy in the absence of elevated KL-6

    PubMed Central

    2014-01-01

    Background Pneumonitis is a rare complication of bacillus Calmette-Guerin (BCG) immunotherapy seen in patients with urothelial cancer following the repeated administration of BCG. However, no case of BCG-induced pleurisy has been reported. Case presentation We here report the first case of pneumonitis with lymphocytic pleurisy following bacillus Calmette-Guerin (BCG) immunotherapy. Although marked T helper cell alveolitis was found by bronchoalveolar lavage and transbronchial biopsies, no acid-fast bacillus could be identified in recovered BALF or pleural effusion. The lymphocyte stimulation test of BCG was strongly positive. However, levels of serum and bronchoalveolar lavage fluid KL-6, a useful marker for hypersensitivity pneumonitis (HP), were within normal ranges. Conclusion We speculate that the pathogenesis of our case may be a hypersensitive reaction to the proteic component of BCG entering the lung and pleural space, which is different from the etiology of the common type of HP. PMID:24593234

  2. Sarcoidosis: correlation of delayed hypersensitivity, MLC reactivity and lymphocytotoxicity with disease activity

    PubMed Central

    Broom, B. C.; Maclaurin, B. P.

    1973-01-01

    Delayed skin reactivity to a battery of antigens was assessed for a series of sarcoidosis patients and closely matched controls. It was compared with the proliferative and cytotoxic capacity of corresponding blood lymphocyte preparations after challenge in mixed lymphocyte culture with an allogeneic lymphoma cell line. Skin anergy to all antigens tested was found only within the patient group having definitely active disease. These patients also showed depression of lymphocyte proliferative response in the in vitro test system as compared to matched controls and to patients with apparently inactive disease. Both of these differences were statistically significant. Skin reactivity to tuberculin was significantly depressed for the whole sarcoidosis group (both active and inactive) as compared to the control group and significant impairment of capacity to develop cytotoxicity in vitro was also found in comparison of these same groups. The results obtained confirm the association of impaired delayed skin hypersensitivity in sarcoidosis with diminished lymphocyte reactivity in vitro, especially when the disease is active. The reduced cytotoxic capacity of sarcoid lymphocytes in vitro may reflect a comparable in vivo impairment and partly explain the depressed skin tests and also contribute to the protracted nature of the disease because of failure to eradicate the postulated `sarcoid agent'. PMID:4271772

  3. Correlation between atopy and hypersensitivity reactions during therapy with three different TNF-alpha blocking agents in rheumatoid arthritis.

    PubMed

    Benucci, M; Manfredi, M; Saviola, G; Baiardi, P; Campi, P

    2009-01-01

    no correlation between the atopic status and the incidence of hypersensitivity reactions during the first year of therapy with three different TNF-alpha blocking agents.

  4. Herbicide (Roundup) pneumonitis.

    PubMed

    Pushnoy, L A; Avnon, L S; Carel, R S

    1998-12-01

    A case of acute intoxication presented as toxic pneumonitis after exposure to Roundup (glyphosate) (Solaris Group, Monsanto; San Ramon, CA) herbicide in an agriculture worker. The correct etiologic factor causing this specific clinical picture was identified only 2 weeks later, after a thorough occupational history was taken and meticulous delineation of the working conditions and exposures of the involved worker were made. As a rule, occupational related diseases are not readily elucidated by nonoccupational physicians. However, most acute intoxication events are first encountered by such physicians. In these situations, rapid and comprehensive evaluation is necessary in order to clearly identify the causative agent(s) and to initiate the appropriate treatment. Consulting occupational physicians at this early stage may facilitate early and accurate diagnosis.

  5. Drug hypersensitivity.

    PubMed

    Yawalkar, N

    2009-01-01

    Drug hypersensitivity represents an immune-mediated reaction to a drug. Although several drug hypersensitivity reactions are confined to the skin and rather mild, some may be life threatening and also involve further organs such as liver, kidney and bone marrow. The exact pathogenesis of many drug hypersensitivity reactions is still obscure. In this review the concepts on how small molecular drugs can activate the immune system are discussed and the hapten, prohapten and p-i concept are explained. Furthermore, the classification of drug hypersensitivity reactions and some common and severe clinical manifestations of drug-induced T cell mediated reactions are presented.

  6. Fatal cadmium-induced pneumonitis.

    PubMed

    Seidal, K; Jörgensen, N; Elinder, C G; Sjögren, B; Vahter, M

    1993-12-01

    A previously relatively healthy 78-year-old man was exposed to cadmium fumes during brazing with cadmium-containing silver solder. He developed severe chemical pneumonitis and died 25 d after exposure.

  7. HYPERSENSITIVITY PNEUMONITIS IN A METAL-WORKING ENVIRONMENT. (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...

  8. HYPERSENSITIVITY PNEUMONITIS IN A METAL-WORKING ENVIRONMENT. (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...

  9. Signs, symptoms, and pathophysiology of Pneumocystis carinii pneumonitis.

    PubMed

    Hughes, W T; Sanyal, S K; Price, R A

    1976-10-01

    In 80 patients with Pneumocystis pneumonitis, the intial signs and symptoms of infection were usually fever and cough, followed by tachypnea and coryza. Flaring of the nasal alae and cyanosis occurred later. Blood gas composition was markedly altered in its acid-base profile in most patients at admission. There was moderate to severe respiratory alkalosis and hypoxia. Clinical manifestations were correlated with the extent of histopathologic changes in the lung. (Deprivation of protein in the diet of rats provoked P. carinii infection.) P. carinii infection was found in children with kwashiorkor; evidence of protein-calorie malnutrition is closely associated with P. carinii pneumonitis in children wiht cancer and other primary diseases. P. carinii pneumonitis proved unique in that the causative organisms remained limited to the lungs even in fatal cases. No toxins have been identified, and systemic effects of the infection were only those that could be related to hypoxia and fever.

  10. THE HYPERSENSITIVITY PNEUMONITIS DIAGNOSTIC INDEX: USE OF NON-INVASIVE TESTING TO DIAGNOSE HYPERSENSITIVITY PNEUMONITIS IN METALWORKERS. (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. THE HYPERSENSITIVITY PNEUMONITIS DIAGNOSTIC INDEX: USE OF NON-INVASIVE TESTING TO DIAGNOSE HYPERSENSITIVITY PNEUMONITIS IN METALWORKERS. (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...

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

    PubMed

    Song, Hao; Yu, Jin-ming

    2009-01-01

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

  13. 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.

  14. 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

  15. Copper hypersensitivity.

    PubMed

    Fage, Simon W; Faurschou, Annesofie; Thyssen, Jacob P

    2014-10-01

    The world production of copper is steadily increasing. Although humans are widely exposed to copper-containing items on the skin and mucosa, allergic reactions to copper are only infrequently reported. To review the chemistry, biology and accessible data to clarify the implications of copper hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common. As a metal, it possesses many of the same qualities as nickel, which is a known strong sensitizer. Cumulative data on subjects with presumed related symptoms and/or suspected exposure showed that a weighted average of 3.8% had a positive patch test reaction to copper. We conclude that copper is a very weak sensitizer as compared with other metal compounds. However, in a few and selected cases, copper can result in clinically relevant allergic reactions.

  16. Drug hypersensitivity.

    PubMed

    Bircher, Andreas J

    2014-01-01

    Before the arrival of modern pharmacotherapy, drug hypersensitivity reactions were virtually unknown. Toxicity from the many plant-, animal- and inorganic material-derived remedies must have been much more common. One famous example is the intoxications from mercury, which has been used in many ailments, but particularly for the treatment of syphilis. It was only in the 19th century when more and more active principles from e.g. plants were identified, and when the observations of skin reactions became more prevalent. In 1877, Heinrich Köbner used for the first time the term 'drug exanthema' (Arznei-Exanthem). Since then, many different types of exanthemas from the mild macular-papular forms to the severe life-threatening bullous exanthemas such as toxic epidermal necrolysis have been observed from numerous drugs. The systematic investigation of severe drug reactions has only started in the second half of the 20th century, parallel to the increasing knowledge in immunology. Drug hypersensitivity reactions still remain one of the most challenging problems in allergology due to their manifold clinical manifestations and their very diverse pathophysiology. The introduction of new drugs and in turn the emergence of new hypersensitivity reactions will remain a challenge in the future. © 2014 S. Karger AG, Basel.

  17. 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.

  18. Elevated expression of c-fos in central nervous system correlates with visceral hypersensitivity in irritable bowel syndrome (IBS): a new target for IBS treatment.

    PubMed

    Zhang, Ru; Zou, Ning; Li, Ji; Lv, Hong; Wei, Jing; Fang, Xiu-Cai; Qian, Jia-Ming

    2011-08-01

    Although visceral hypersensitivity is a major pathophysiological feature of irritable bowel syndrome (IBS), its molecular mechanisms are still poorly understood. c-fos is a well-established marker of cell activation. Accumulating evidence demonstrates that norepinephrine (NE) system is dysregulated in IBS; however, very little is known on its mechanism. It is our hypothesis that elevated expression of c-fos in central nervous system (CNS) correlates with visceral hypersensitivity in rat model of IBS. Furthermore, we explored the changes of NE system in IBS patients. The rat model of IBS was induced by heterotypic chronic and acute stress. Tissues obtained from rat model were analyzed for c-fos levels in CNS (frontal lobe, hippocampus, cornu dorsale) and colon by immunohistochemistry. Real-time reverse transcription polymerase chain reaction was used to detect tyrosine hydroxylase (TH) in the colonic tissues obtained from IBS patients. The rat model of IBS was associated with increased expression of c-fos in different parts of CNS (P = 0.001, P = 0.002, and P = 0.002, respectively), but normal in colon (P = 0.207). The clinical parameters (colonic motility and sensation) of rat model were significantly correlated with elevated c-fos in CNS (P < 0.05). Enterochromaffin cells and serotonin in colon were related to the elevated c-fos in CNS (P < 0.05). The TH messenger ribonucleic acid (mRNA level of IBS-D patients was almost four times as much as that of controls. Elevated expression of c-fos in CNS might be one of key mechanisms in etiology of IBS. Therefore, regulation of CNS activation could be a major targeting effect when treating IBS patients.

  19. [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.

  20. Pro-Brain Natriuretic Peptide and Troponin T-Hypersensitivity Levels Correlate With the Severity of Liver Dysfunction in Liver Cirrhosis.

    PubMed

    Zhao, Jiancheng; Li, Sai; Ren, Linan; Guo, Xiaozhong; Qi, Xingshun

    2017-08-01

    Increased pro-brain natriuretic peptide (pro-BNP) or troponin T-hypersensitivity (TnT-HSST) levels are common in liver cirrhosis. We conducted a retrospective observational study aimed to evaluate the correlation of pro-BNP and TnT-HSST levels with the clinical characteristics, laboratory data and in-hospital outcomes of patients with liver cirrhosis. We selected cirrhotic patients admitted to our hospital between January 2011 and June 2014. All eligible patients had pro-BNP or TnT-HSST data, or both. The pro-BNP and TnT-HSST data were further divided according to the presence of cardiac diseases. The prevalence of pro-BNP level >900pg/mL was 41.72% (63 of 151 patients). The prevalence of TnT-HSST level >0.05ng/mL was 11.22% (45 of 401 patients). In the overall analysis, pro-BNP level significantly correlated with red blood cell (RBC), platelet, ascites, blood urea nitrogen (BUN), creatinine (Cr), Child-Pugh score, model for end-stage liver disease (MELD) score and in-hospital death; TnT-HSST level significantly correlated with white blood cell, ascites, albumin (ALB), BUN, Cr, Child-Pugh score, MELD score and in-hospital death. In patients with cardiac diseases, pro-BNP level significantly correlated with RBC, ascites, BUN, Cr, Child-Pugh score and MELD score; TnT-HSST level significantly correlated with sex, ascites, white blood cell, ALB, BUN, Cr, Child-Pugh score, MELD score and in-hospital death. In patients without cardiac diseases, pro-BNP level significantly correlated with ascites, RBC, platelet, BUN, Cr, MELD score and in-hospital death; TnT-HSST level significantly correlated with age, ascites, RBC, ALB, BUN, Cr, Child-Pugh score, MELD score and in-hospital death. Pro-BNP and TnT-HSST levels significantly correlated with the severity of liver dysfunction and in-hospital mortality in cirrhosis. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  1. Acute respiratory distress syndrome complicating generalized pustular psoriasis (psoriasis-associated aseptic pneumonitis).

    PubMed

    Kluger, Nicolas; Bessis, Didier; Guillot, Bernard; Girard, Céline

    2011-06-01

    Generalized pustular and/or erythrodermic psoriasis may have severe or even lethal complications. A peculiar noninfectious acute respiratory distress syndrome (so-called "sterile pneumonitis") has been described in generalized pustular psoriasis and/or erythrodermic psoriasis. We report a new case in a 14-year-old girl with a long history of pustular psoriasis and review the published work on this complication. The girl developed sterile pneumonitis during a disease flare-up, and high-dose corticosteroid therapy was quickly initiated. Within a few days, her clinical and radiological status was dramatically improved. The pathogenesis of aseptic pneumonitis is unknown, but various proinflammatory cytokines have been implicated, especially tumor necrosis factor-alpha, which could play a role in the recruitment of leukocytes to the lung. This complication has rarely been reported but should be more widely known as the differential diagnoses include congestive heart failure, acute lung infection related or unrelated to immunosuppressive therapy, and drug hypersensitivity reaction. Early recognition would avoid delays in the correct management of this potentially lethal complication, which requires high-dose systemic corticosteroid therapy. Copyright © 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  2. 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.

  3. 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.

  4. Affinity of Avr2 for tomato cysteine protease Rcr3 correlates with the Avr2-triggered Cf-2-mediated hypersensitive response.

    PubMed

    Van't Klooster, John W; Van der Kamp, Marc W; Vervoort, Jacques; Beekwilder, Jules; Boeren, Sjef; Joosten, Matthieu H A J; Thomma, Bart P H J; De Wit, Pierre J G M

    2011-01-01

    The Cladosporium fulvum Avr2 effector is a novel type of cysteine protease inhibitor with eight cysteine residues that are all involved in disulphide bonds. We have produced wild-type Avr2 protein in Pichia pastoris and determined its disulphide bond pattern. By site-directed mutagenesis of all eight cysteine residues, we show that three of the four disulphide bonds are required for Avr2 stability. The six C-terminal amino acid residues of Avr2 contain one disulphide bond that is not embedded in its overall structure. Avr2 is not processed by the tomato cysteine protease Rcr3 and is an uncompetitive inhibitor of Rcr3. We also produced mutant Avr2 proteins in which selected amino acid residues were individually replaced by alanine, and, in one mutant, all six C-terminal amino acid residues were deleted. We determined the inhibitory constant (K(i) ) of these mutants for Rcr3 and their ability to trigger a Cf-2-mediated hypersensitive response (HR) in tomato. We found that the two C-terminal cysteine residues and the six amino acid C-terminal tail of Avr2 are required for both Rcr3 inhibitory activity and the ability to trigger a Cf-2-mediated HR. Individual replacement of the lysine-17, lysine-20 or tyrosine-21 residue by alanine did not affect significantly the biological activity of Avr2. Overall, our data suggest that the affinity of the Avr2 mutants for Rcr3 correlates with their ability to trigger a Cf-2-mediated HR.

  5. [Hypersensitivity reactions to insulin].

    PubMed

    Becerril-Ángeles, Martín; Moctezuma-Trejo, Cristina; Espinosa-Larrañaga, Francisco

    2012-01-01

    Hypersensitivity reactions to insulin are infrequent, yet of clinical importance. The mechanisms of hypersensitivity involved can be of three types: I, III and IV. To describe the pathophysiology of hypersensitivity to insulin, its clinical features and diagnostic and therapeutic approach, that help identify the cases of allergy to insulin and begin a treatment, or if necessary, to refer patients to a specialists or appropriate medical attention. An electronic search of papers related to insulin hypersensitivity was performed in PubMed and the articles selected were those considered the most relevant for this review. Thirty eight papers about pathophysiology, mechanisms of injury and the different types of insulin involved in hypersensitivity reactions were included. Likewise, information for the diagnosis of insulin hypersensitivity and some options of treatment for first contact physicians or the referral of patients to specialists in endocrinology and allergy were included. Insulin hypersensitivity has a low prevalence and diverse clinical manifestations. The different types of insulin suitable allow the majority of cases of hypersensitivity to continue the treatment in a efficient and flexible manner.

  6. Treating dentin hypersensitivity

    PubMed Central

    Cunha-Cruz, Joana; Wataha, John C.; Zhou, Lingmei; Manning, Walter; Trantow, Michael; Bettendorf, Meishan M.; Heaton, Lisa J.; Berg, Joel

    2011-01-01

    Background Methods used by dental practitioners to diagnose and treat dentin hypersensitivity are not well documented. The authors conducted a survey of dentists in the Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry (PRECEDENT) to ascertain the treatment methods they used. Methods Via an Internet survey, the authors collected data regarding methods used for diagnosis and treatment of dentin hypersensitivity from 209 Northwest PRECEDENT dentists. Results The PRECEDENT dentists indicated that they most often used fluoride varnishes and gels, advice regarding toothbrushing and diet, bonding agents, restorative materials and glutaraldehyde/2-hydroxyethyl methacrylate (HEMA) to treat dentin hypersensitivity. They reported that the most successful treatments were fluorides, glutaraldehyde/HEMA, bonding agents, potassium nitrates and restorative treatments; they considered observation, advice regarding toothbrushing and diet and laser therapy to be the least successful. Dentists listed fluorides, calcium phosphates, glutaraldehyde/HEMA and bonding agents as the treatments most desirable for inclusion in a future randomized clinical trial of dental hypersensitivity treatments. Conclusions Dentists rely on patients to assess the severity of dentin hypersensitivity. Modalities for the diagnosis and treatment of hypersensitivity are diverse. Methods used to diagnose and treat dentin hypersensitivity in practice are challenging to justify. Clinical Implications Practitioners should be aware of the diversity of methods available for diagnosing and treating dentin hypersensitivity as they manage the care of their patients with this condition. PMID:20807910

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

    SciTech Connect

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

    2011-08-01

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

  8. Pneumonic Plague Transmission, Moramanga, Madagascar, 2015

    PubMed Central

    Ramasindrazana, Beza; Andrianaivoarimanana, Voahangy; Rakotondramanga, Jean Marius; Birdsell, Dawn N.; Ratsitorahina, Maherisoa

    2017-01-01

    During a pneumonic plague outbreak in Moramanga, Madagascar, we identified 4 confirmed, 1 presumptive, and 9 suspected plague case-patients. Human-to-human transmission among close contacts was high (reproductive number 1.44) and the case fatality rate was 71%. Phylogenetic analysis showed that the Yersinia pestis isolates belonged to group q3, different from the previous outbreak. PMID:28221119

  9. Current challenges in the development of vaccines for pneumonic plague

    PubMed Central

    Smiley, Stephen T

    2008-01-01

    Inhalation of Yersinia pestis bacilli causes pneumonic plague, a rapidly progressing and exceptionally virulent disease. Extensively antibiotic-resistant Y. pestis strains exist and we currently lack a safe and effective pneumonic plague vaccine. These facts raise concern that Y. pestis may be exploited as a bioweapon. Here, I review the history and status of plague vaccine research and advocate that pneumonic plague vaccines should strive to prime both humoral and cellular immunity. PMID:18324890

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

    PubMed

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

    2004-01-01

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

  11. Hypersensitivity reaction to azathioprine.

    PubMed

    Fields, C L; Robinson, J W; Roy, T M; Ossorio, M A; Byrd, R P

    1998-05-01

    Adverse drug reactions can vary from a simple rash to anaphylactic shock. While certain medications including the penicillins are well known to cause such reactions, other drugs are not as commonly recognized. Azathioprine hypersensitivity reactions tend to be benign and self-limiting with cessation of drug ingestion. We report a patient who had a hypersensitivity reaction to azathioprine, which manifested as distributive shock that mimicked sepsis. We also reviewed the English language literature for risk factors for a hypersensitivity reaction to azathioprine and its possible mechanism.

  12. Oral Hypersensitivity Reactions

    MedlinePlus

    ... of substances. The most common causes are food, food additives, drugs, oral hygiene products, and dental materials. Q: Are there any specific foods that are more commonly implicated in intraoral hypersensitivity ...

  13. 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. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Drug hypersensitivity syndrome.

    PubMed

    Bonnetblanc, J M

    1993-01-01

    Some types of hypersensitivity to drugs are defined either by the generic name of the drug or descriptive terms. They are sometimes assimilated to pseudolymphoma because the causative drugs are often the same, although the eruption lacks clinical and histopathological criteria of pseudolymphoma. It is then suggested to use 'idiosyncratic drug hypersensitivity syndrome' to define this type of drug reaction. As the skin and other organs may be involved, a generic name would help to determine a better definition and a surveillance program.

  15. Collagen gene expression in radiation interstitial pneumonitis

    SciTech Connect

    Bai Yun-hong; Wang, De-wen; Cui Cai-bin

    1994-12-31

    By using type I and type III collagen cDNA probe and cDNA-mRNA in situ hybridization, we observed the changes of rat lung {alpha} 1(I) and {alpha} 1(III) collagen gene expression in radiation interstitial pneumonitis. The results showed that the expressed cell of type I and type III collagen were scattered within the fibroblasts in the thickened interalveolar walls. The type I and type III collagen mRNA content in irradiated animals were higher than those in the controls at 0.5, 1, 2, 3, 6, and 12 months. 10 refs., 4 figs., 1 tab.

  16. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Afatinib-Induced Acute Fatal Pneumonitis in Metastatic Lung Adenocarcinoma

    PubMed Central

    Yoo, Sang Hoon; Ryu, Jin Ah; Kim, Seo Ree; Oh, Su Yun; Jung, Gu Sung; Lee, Dong Jae; Kwak, Bong Gyu; Nam, Yu Hyun; Kim, Kyung Hyun

    2016-01-01

    Afatinib is an oral tyrosine kinase inhibitor (TKI) that inhibit Endothelial Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4. The common side effects of EGFR TKI are rash, acne, diarrhea, stomatitis, pruritus, nausea, and loss of appetite. Drug induced pneumonitis is the less common adverse effects of EGFR TKI. Afatinib, 2nd generation EGFR TKI is anticipated to overcome drug resistance from 1st generation EGFR TKI according to preclinical study, and several studies are being conducted to compare clinical efficacy between 1st and 2nd EGFR TKI. Several cases of rug induced acute fatal pneumonitis were reported after use of erlotinib or gefitinib. However, a case of acute fatal pneumonitis associated with afatinib was note reported except drug induced pneumonitis in other clinical study. Here, we present a cases of acute severe pneumonitis related with afatinib in metastatic lung adenocarcinoma with literature review. PMID:27900074

  18. Virus antibody levels and delayed hypersensitivity in rheumatoid arthritis.

    PubMed Central

    Phillips, P E; Waxman, J; Hirshaut, Y; Kaplan, M H

    1976-01-01

    Epstein-Barr virus and cytomegalovirus antibody levels were not higher in patients with rheumatoid arthritis compared to matched controls. Delayed hypersensitivity, measured by skin test reactivity, was depressed in rheumatoid arthritis. There was no correlation between virus antibody titres and delayed hypersensitivity. PMID:182092

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

    PubMed

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

    2016-01-01

    Peptide signaling in plants is involved in regulating development, (1,2) ensuring cross pollination through initiation of self-incompatibility (4) and assisting with recognition of beneficial (nitrogen fixing bacteria (5)) or unfavorable organisms (pathogens (6) or herbivores (7)). 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.

  20. 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

  1. 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

  2. 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

  3. Sensory hypersensitivity in children with high-functioning pervasive developmental disorder.

    PubMed

    Futoo, Eri; Miyawaki, Dai; Goto, Ayako; Okada, Yu; Asada, Nobuyoshi; Iwakura, Yoshihiro; Yanagihara, Erika; Inoue, Koki

    2014-12-01

    Studies have shown that children with pervasive developmental disorder (PDD) have high rates of sensory hypersensitivity. In addition, a few recent studies suggested that sensory hypersensitivity was related to anxiety or depression. However, most studies had methodological limitations because they included children with mental retardation and did not examine broadband psychopathology. Therefore, the purpose of this study was to examine the prevalence of sensory hypersensitivity in children with high-functioning PDD (HFPDD) and the correlation among sensory hypersensitivity, various characteristics, and broadband psychopathology. We assessed 132 children with HFPDD (aged 6-15 years, 75% male) that were divided into sensory hypersensitivity (HS) and sensory non-hypersensitivity (non-HS) groups. A logistic regression model was used to examine correlations among sensory hypersensitivity, age, gender, PDD subtypes, socioeconomic status, and broadband psychopathology, including symptoms of anxiety and depression. Of the 132 children with HFPDD, 65.9% (n = 87) were categorized as HS and 34.1% (n = 45) as non-HS. The most common sensory hypersensitivity was auditory. Logistic regression analyses revealed that sensory hypersensitivity in HFPDD was significantly associated with autistic disorder and symptoms of anxiety and depression. Majority of children with HFPDD exhibited sensory hypersensitivity. Our findings suggested that sensory hypersensitivity may be a core feature of HFPDD and is possibly correlated to symptoms of anxiety and depression. We propose that sensory hypersensitivity in children with PDD should be aggressively assessed.

  4. IMMUNOLOGICAL REACTIONS OF PNEUMONIC PLEURAL FLUIDS

    PubMed Central

    Finland, Maxwell

    1932-01-01

    Pleuritic exudates from patients with lobar pneumonia may be sterile or infected. Sterile fluids, at or about the time of crisis, contain actively acquired antibodies similar to those in the blood serum. Infected fluids do not contain such antibodies, presumably because of the presence in them of large amounts of soluble specific substance. Sterile fluids from patients treated with immune sera have both horse serum and antibodies similar to those injected. Infected fluids from serum-treated cases contain horse serum and such heterologous antibodies as were contained in the therapeutic sera together with homologous soluble specific substance. The concentration of horse serum and antibodies in pneumonic fluids is usually the same or somewhat less than that of the corresponding blood sera. PMID:19869983

  5. Pneumonic Plague Outbreak, Northern Madagascar, 2011

    PubMed Central

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

    2015-01-01

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

  6. Al Eskan disease: Desert Storm pneumonitis.

    PubMed

    Korényi-Both, A L; Korényi-Both, A L; Molnár, A C; Fidelus-Gort, R

    1992-09-01

    The authors observed an acute desert-related disease when the mixture of the fine Saudi sand dust and pigeon droppings triggered a hyperergic lung condition. It was further aggravated by various kinds of organic pathogenic components contributing to an opportunistic infection of the lung. These all lead to the recognition of a new clinicopathological entity, Desert Storm pneumonitis or Al Eskan disease. For the first time, the Saudi sand dust's elemental composition was studied by ultrastructural and microanalytical means. The authors concluded that, contrary to previous beliefs, sand particles less than 1 microns (0.1 microns to 0.25 microns) in diameter are present in substantial quantities in the Saudi sand and are pathogenic, causing hyperergia. Pathogenesis of the sand dust, induced hyperergia, and its immunopathologic background are highlighted.

  7. 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.

  8. Multiple drug hypersensitivity syndrome.

    PubMed

    Chiriac, Anca M; Demoly, Pascal

    2013-08-01

    The multiple drug hypersensitivity syndrome (MDH) is a distinct clinical entity, different from cross-reactivity and flare-up reactions. Following its initial description in 1989 by Sullivan et al., several authors have addressed the issues surrounding this peculiar form of drug hypersensitivity. Whether this syndrome is single or can be further classified in several entities is still a matter of debate. Case reports, case series or studies involving large populations on MDH are few. The use of this term in the literature is heterogeneous, and the definitions variable. Given the major advances in the study of drug hypersensitivities in general, and ongoing research regarding severe cutaneous adverse reactions in particular, careful study of the subgroup of patients with demonstrated immunological basis of MDH has enabled the generation of possible pathogenetic hypotheses. Together with the studies (despite their limitations) to estimate the prevalence of this syndrome in adult and paediatric patients these emerging data need confirmation through larger studies with well defined populations. Bringing together the experience of groups involved in the field of drug allergy should help to move knowledge regarding this peculiar form of drug hypersensitivity forward.

  9. Differential responses of primary auditory cortex in autistic spectrum disorder with auditory hypersensitivity.

    PubMed

    Matsuzaki, Junko; Kagitani-Shimono, Kuriko; Goto, Tetsu; Sanefuji, Wakako; Yamamoto, Tomoka; Sakai, Saeko; Uchida, Hiroyuki; Hirata, Masayuki; Mohri, Ikuko; Yorifuji, Shiro; Taniike, Masako

    2012-01-25

    The aim of this study was to investigate the differential responses of the primary auditory cortex to auditory stimuli in autistic spectrum disorder with or without auditory hypersensitivity. Auditory-evoked field values were obtained from 18 boys (nine with and nine without auditory hypersensitivity) with autistic spectrum disorder and 12 age-matched controls. Autistic disorder with hypersensitivity showed significantly more delayed M50/M100 peak latencies than autistic disorder without hypersensitivity or the control. M50 dipole moments in the hypersensitivity group were larger than those in the other two groups [corrected]. M50/M100 peak latencies were correlated with the severity of auditory hypersensitivity; furthermore, severe hypersensitivity induced more behavioral problems. This study indicates auditory hypersensitivity in autistic spectrum disorder as a characteristic response of the primary auditory cortex, possibly resulting from neurological immaturity or functional abnormalities in it.

  10. 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.

  11. MZF-1 and DbpA interact with DNase I hypersensitive sites that correlate with expression of the human MUC1 mucin gene

    SciTech Connect

    Shiraga, Toshiyuki; Winpenny, John P.; Carter, Emma J.; McCarthy, Victoria A.; Hollingsworth, Michael A.; Harris, Ann . E-mail: ann.harris@paediatrics.ox.ac.uk

    2005-08-01

    The MUC1 mucin is a large membrane-tethered glycoprotein that shows differential expression in many adenocarcinomas, where it contributes to their invasive and metastatic properties. We previously identified DNase I hypersensitive sites at -750 and -250 bp in the human MUC1 gene promoter and showed concordance between the -250 site and MUC1 mRNA levels in vivo. Transient expression assays using promoter constructs, in which the core DHS was deleted, to drive reporter gene expression revealed in vivo evidence for their activity. DNase I footprinting using nuclear extracts from HPAF human pancreatic carcinoma cells and MCF7 breast carcinoma cells identified three protein-binding elements in these regions (-250FP1, FP2 and -750FP). Electrophoretic mobility shift assays detected several complexes between HPAF nuclear proteins and labeled FP DNA probes. Southwestern blots and UV cross-linking experiments identified myeloid zinc finger-1 (MZF-1) as a candidate transcription factor among proteins binding to the -250FP1 and FP2 sequences. Another candidate that was identified by screening an HPAF cDNA expression library with the -250FP1 probe is DNA binding protein A (DbpA). Exogenous DbpA expression in COS-7 cells was accompanied by upregulation of MUC1 promoter activity via the -250 DHS, suggesting that DbpA binding to the -250 DHS can influence human MUC1 gene expression.

  12. Intranasal Administration of an Inactivated Yersinia pestis Vaccine with Interleukin-12 Generates Protective Immunity against Pneumonic Plague ▿ #

    PubMed Central

    Kumar, Devender; Kirimanjeswara, Girish; Metzger, Dennis W.

    2011-01-01

    Inhalation of Yersinia pestis causes pneumonic plague, which rapidly progresses to death. A previously licensed killed whole-cell vaccine is presently unavailable due to its reactogenicity and inconclusive evidence of efficacy. The present study now shows that vaccination intranasally (i.n.) with inactivated Y. pestis CO92 (iYp) adjuvanted with interleukin-12 (IL-12) followed by an i.n. challenge with a lethal dose of Y. pestis CO92 prevented bacterial colonization and protected 100% of mice from pneumonic plague. Survival of the vaccinated mice correlated with levels of systemic and lung antibodies, reduced pulmonary pathology and proinflammatory cytokines, and the presence of lung lymphoid cell aggregates. Protection against pneumonic plague was partially dependent upon Fc receptors and could be transferred to naïve mice with immune mouse serum. On the other hand, protection was not dependent upon complement, and following vaccination, depletion of CD4 and/or CD8 T cells before challenge did not affect survival. In summary, the results demonstrate the safety, immunogenicity, and protective efficacy of i.n. administered iYp plus IL-12 in a mouse model of pneumonic plague. PMID:21880856

  13. [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.

  14. 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

  15. [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.

  16. Management Strategies for Clopidogrel Hypersensitivity.

    PubMed

    Beavers, Craig J; Carris, Nicolas W; Ruf, Kathryn M

    2015-06-01

    Clopidogrel is a cornerstone of dual antiplatelet therapy. Hypersensitivity reactions potentially limit the use of this treatment and present a significant clinical challenge. The authors have developed recommendations for the management of clopidogrel hypersensitivity with consideration for the etiology, pathophysiology, and critical evaluation of potential management strategies. The clopidogrel hypersensitivity reaction is complex in mechanism and presents generally around day 5 of treatment. Generalized reactions are most common, but the reaction may also be localized or systemic. Screening patients for hypersensitivity is not always possible because the type IV delayed reaction is not detected reliably by conventional skin prick, intradermal challenge, or patch testing. Proposed strategies for management of clopidogrel hypersensitivity include treatment of the reaction with corticosteroids, clopidogrel desensitization, substituting an alternative P2Y12 inhibitor, or clopidogrel avoidance. The safety, efficacy, and cost of each potential strategy must be considered when managing a patient with clopidogrel hypersensitivity.

  17. [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.

  18. Interstitial pneumonitis induced by bicalutamide given for prostate cancer.

    PubMed

    Masago, Toshihiko; Watanabe, Takeshi; Nemoto, Ryosuke; Motoda, Kinya

    2011-12-01

    We describe interstitial pneumonitis induced by bicalutamide prescribed to treat prostate cancer. A 78-year-old man with severe lower paralysis and a bladder/rectal disorder was referred to our hospital. Prostate-specific antigen was elevated to 1418 ng/mL at that time and magnetic resonance imaging revealed multiple bone metastases. A rectal examination revealed hard nodules in the bilateral lobes of the prostate. We diagnosed prostate cancer without a biopsy, and then maximally blockaded androgens by castration and bicalutamide administration. Eight months later, he was admitted to a local hospital with breathing difficulties, and a computed tomography scan revealed interstitial pneumonitis. A physician concluded that the cause of the interstitial pneumonitis was bicalutamide, which was immediately withdrawn and replaced with prednisolone. The patient recovered over a period of 3 months. Bicalutamide-induced interstitial pneumonitis is quite rare. However, adverse reactions to maximal androgen blockade therapy should be considered and appropriate treatment for interstitial pneumonitis should be promptly initiated, as this condition is reversible.

  19. Pneumonitis and pulmonary fibrosis associated with breast cancer treatments.

    PubMed

    Omarini, Claudia; Thanopoulou, Eirini; Johnston, Stephen R D

    2014-07-01

    To review the available published data regarding the incidence, mechanisms of pathogenesis, clinical presentations and management of pneumonitis caused by anti-cancer treatments (radiotherapy (RT) and systemic agents) that are included in the guidelines of the treatment of breast cancer (BC) and address the issues on the current grading classification of pneumonitis. A literature search was performed between July and October 2013 using PubMed for papers published from January 1989 to October 2013. Any clinical trial, case report, case series, meta-analysis or systematic review that reported on pulmonary toxicity of any BC therapeutic modality was included (only papers published in English). Most of anticancer treatments currently used in the management of BC may induce some degree of pneumonitis that is estimated to have an incidence of 1-3 %. There is an obvious distinction between chemotherapy- and targeted treatment-related lung toxicity. Moreover, the current classification of pneumonitis needs to be modified as there is a clear diversity in grade 2. As pneumonitis is relatively common and reported as side effect of new anticancer agents, physicians need to be aware of the clinical and radiological manifestations of drug- and RT-induced toxicities in patients with BC. A key recommendation is the subdivision of grade 2 cases to two subgroups. We provide an algorithm, along with real life cases as managed in the breast Unit of Royal Marsden Hospital, with the aim to guide physicians in managing all possible eventualities that may come across in clinical practise.

  20. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Transient generalized glucocorticoid hypersensitivity.

    PubMed

    Nicolaides, Nicolas C; Lamprokostopoulou, Agaristi; Polyzos, Alexandros; Kino, Tomoshige; Katsantoni, Eleni; Triantafyllou, Panagiota; Christophoridis, Athanasios; Katzos, George; Dracopoulou, Maria; Sertedaki, Amalia; Chrousos, George P; Charmandari, Evangelia

    2015-12-01

    Transient generalized glucocorticoid hypersensitivity is a rare disorder characterized by increased tissue sensitivity to glucocorticoids and compensatory hypo-activation of the hypothalamic-pituitary-adrenal axis. The condition itself and the underlying molecular mechanisms have not been elucidated. To present the clinical manifestations, endocrinologic evaluation and transcriptomic profile in a patient with transient generalized glucocorticoid hypersensitivity. A 9-year-old girl presented with an 8-month history of clinical manifestations suggestive of Cushing syndrome. Endocrinologic evaluation revealed undetectable 08:00 h ACTH (<1 pg/mL) and cortisol (0·025 μg/dL) concentrations, which remained decreased throughout the 24-h period and did not respond to stimulation with ovine CRH. The disease gradually resolved spontaneously over the ensuing 3 months. Sequencing of the human glucocorticoid receptor gene revealed no mutations or polymorphisms. Western blot analysis in peripheral blood mononuclear cells revealed equal protein expression of hGRα of the patient in the disease and postresolution phases compared with a control subject. Transcriptomic analysis in peripheral blood mononuclear cells in the disease and postresolution phases identified 903 differentially expressed genes. Of these, 106 genes were up-regulated and 797 were down-regulated in the disease compared with the resolution phase. Bioinformatics analysis on the differentially expressed gene networks revealed Nuclear Factor-κB as the predominant transcription factor influencing the expression of the majority of differentially expressed genes. Our findings indicate that a transient postreceptor defect, or a virus- or bacterium-encoded molecule, may have enhanced glucocorticoid signal transduction, leading to transient generalized glucocorticoid hypersensitivity and hypo-activation of the HPA axis. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

  2. 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

  3. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Pneumonitis), Live Chlamydia. 113.71 Section 113.71 Animals and Animal Products ANIMAL AND PLANT HEALTH... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall be...

  4. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Pneumonitis), Live Chlamydia. 113.71 Section 113.71 Animals and Animal Products ANIMAL AND PLANT HEALTH... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall be...

  5. Multiple Drug Hypersensitivity

    PubMed Central

    Pichler, Werner J.; Srinoulprasert, Yuttana; Yun, James; Hausmann, Oliver

    2017-01-01

    Multiple drug hypersensitivity (MDH) is a syndrome that develops as a consequence of massive T-cell stimulations and is characterized by long-lasting drug hypersensitivity reactions (DHR) to different drugs. The initial symptoms are mostly severe exanthems or drug rash with eosinophilia and systemic symptoms (DRESS). Subsequent symptoms due to another drug often appear in the following weeks, overlapping with the first DHR, or months to years later after resolution of the initial presentation. The second DHR includes exanthema, erythroderma, DRESS, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hepatitis, and agranulocytosis. The eliciting drugs can be identified by positive skin or in vitro tests. The drugs involved in starting the MDH are the same as for DRESS, and they are usually given in rather high doses. Fixed drug combination therapies like sulfamethoxazole/trimethoprim or piperacillin/tazobactam are frequently involved in MDH, and 30–40% of patients with severe DHR to combination therapy show T-cell reactions to both components. The drug-induced T-cell stimulation appears to be due to the p-i mechanism. Importantly, a permanent T-cell activation characterized by PD-1+/CD38+ expression on CD4+/CD25low T cells can be found in the circulation of patients with MDH for many years. In conclusion, MDH is a drug-elicited syndrome characterized by a long-lasting hyperresponsiveness to multiple, structurally unrelated drugs with clinically diverse symptoms. PMID:28315874

  6. Drug-induced Pneumonitis Following the Administration of TAS-102

    PubMed Central

    Hasegawa, Yoshikazu; Ota, Takayo; Tsukuda, Hiroshi; Suzumura, Tomohiro; Fukuoka, Masahiro

    2016-01-01

    A 59-year-old woman, diagnosed with advanced rectal cancer, presented with a low-grade fever and dyspnea on exertion after the 2nd cycle of TAS-102. TAS-102 has promising efficacy in patients with metastatic colorectal cancer. A CT scan revealed mosaic patterns with bilateral ground-glass opacities. The drug lymphocyte stimulation test for TAS-102 was strongly positive and serum β-D glucan level was elevated. The clinical course was compatible with TAS-102-induced pneumonitis combined with pneumocystis pneumonia (PCP). We herein report a rare case of drug-induced pneumonitis in a patient receiving TAS-102 in combination with PCP. PMID:27725548

  7. Symptom hypersensitivity to acid infusion is associated with hypersensitivity of esophageal contractility.

    PubMed

    Bhalla, Vikas; Liu, Jianmin; Puckett, James L; Mittal, Ravinder K

    2004-07-01

    Several investigators have observed that repeated acid infusions induce stronger symptoms (symptom hypersensitivity). The goal of our study was to determine whether symptom hypersensitivity is associated with esophageal contractile hypersensitivity. Subjects with chronic heartburn symptoms underwent simultaneous pressure and ultrasound imaging of esophagus. Normal saline and 0.1 N HCl were sequentially infused into the esophagus, and subjects scored heartburn symptoms on a 1-10 scale. Saline and HCl infusions were repeated in 10 subjects with a positive Bernstein test. Esophageal contraction amplitude and duration and muscularis propria thickness were measured using a computerized method during recording. Acid infusion induced heartburn. Esophageal contractions had higher amplitudes (pressure 114.2 +/- 7.0%) and longer duration (116.8 +/- 4.4%) during acid infusion compared with saline infusion. Average muscle thickness was greater during acid infusion than saline infusion (107.0 +/- 2.0%). Sustained esophageal contractions (SECs) were identified during acid infusion. A second acid infusion (acid-2) induced heartburn with shorter latency (93.0 +/- 15.0 vs. 317.0 +/- 43.0 s) and stronger severity (8.5 +/- 0.5 vs. 5.3 +/- 0.8) than the first acid infusion (acid-1). Contraction amplitudes (140.2 +/- 13.0%), average muscle thickness (118.0 +/- 3.3%), and contraction duration (148.5 +/- 5.6 vs. 116.8 +/- 4.4%) were higher during acid-2 than acid-1. Also, numbers of SECs were greater during acid-2 than acid-1 (31 in 8 subjects vs. 11 in 6 subjects). Our data show that acid infusion into esophagus induces esophageal hypersensitivity and that a close temporal correlation exists between symptom hypersensitivity and contractility hypersensitivity.

  8. Gut pain & visceral hypersensitivity

    PubMed Central

    Aziz, Qasim

    2013-01-01

    Visceral pain is a highly complex entity whose experience is variable in health and disease. It can occur in patients with organic disease and also in those without any readily identifiable structural or biochemical abnormality such as in the functional gastrointestinal disorders (FGID). Despite considerable progress in our understanding of the culpable underlying mechanisms significant knowledge gaps remain, representing a significant unmet need in gastroenterology. A key, but not universal, pathological feature is that patients with FGID often display heightened sensitivity to experimental gut stimulation, termed visceral hypersensitivity. A plethora of factors have been proposed to account for this epiphenomenon including peripheral sensitization, central sensitization, aberrant central processing, genetic, psychological and abnormalities within the stress responsive systems. Further research is needed, bringing together complementary research themes from a diverse array of academic disciplines ranging from gastroenterology to nociceptive physiology to functional neuro-imaging, to address this unmet need. PMID:26516496

  9. Hypersensitivity reactions to fluoroquinolones.

    PubMed

    Scherer, Kathrin; Bircher, Andreas J

    2005-01-01

    Fluoroquinolone antibiotics cause immediate and delayed hypersensitivity reactions, and may also affect internal organs and circulating blood cells. The underlying pathomechanisms are only partly understood. The extent of cross-reactivity among different quinolones depends on the type of clinical manifestation and its underlying mechanism. Despite recent advances, reliable diagnostic tests are still lacking. Recent studies have shown quinolone-specific IgE in vitro in more than 50% of patients with immediate-type reactions and a considerable cross-reactivity with related compounds. In maculopapular drug exanthems from ciprofloxacin, specific T-cell clones were identified, and cross-reactivity to related compounds was detected in approximately 50% of the clones. From re-exposure studies in patients with exanthems, cross-reactivity appears to be lower. Cellular tests such as lymphocyte transformation tests are currently not very useful. For prick and intradermal skin tests, widely divergent nonirritant test concentrations have been recommended. Desensitization may be possible in selected patients.

  10. Insect and arachnid hypersensitivity.

    PubMed

    Bevier, D E

    1999-11-01

    Insect hypersensitivity reactions can have a large number of clinical presentations. The majority of reactions are pruritic and involve the short- or sparsely haired areas of the body. Most are associated with eosinophilic infiltration into the skin, often in a perivascular pattern. The diagnosis may be based on compatible clinical signs and improvement with aggressive insect control and, in some cases, confirmation via provocative exposure. Intradermal, prick, or serum testing for allergen-specific IgE can be used to document the presence of reaginic antibodies against insect allergens. Treatments include avoidance, aggressive insect control, and symptomatic support; in some cases, immunotherapy may be useful in decreasing the severity of clinical reactions to insects.

  11. Food hypersensitivity by inhalation

    PubMed Central

    Ramirez, Daniel A; Bahna, Sami L

    2009-01-01

    Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization. PMID:19232116

  12. 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

  13. 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.

  14. Unexpected Symptomatic Pneumonitis Following Breast Tangent Radiation: A Case Report.

    PubMed

    Conway, Jessica L; Long, Karen; Ploquin, Nicolas; Olivotto, Ivo A

    2015-10-22

    Symptomatic radiation pneumonitis (RP) following radiation therapy (RT) to the breast alone is very uncommon. We report a case of an 80-year-old female who presented with fatigue, exertional dyspnea, fever, and cough 11.5 weeks following adjuvant breast RT with tangent fields alone. Imaging was consistent with RP, and she responded to a tapering course of steroids.

  15. Perceptions and reactions with regard to pneumonic plague.

    PubMed

    Rubin, G James; Amlot, Richard; Rogers, M Brooke; Hall, Ian; Leach, Steve; Simpson, John; Wessely, Simon

    2010-01-01

    We assessed perceptions and likely reactions of 1,005 UK adults to a hypothetical terrorist attack involving pneumonic plague. Likely compliance with official recommendations ranged from good (98% would take antimicrobial drugs) to poor (76% would visit a treatment center). Perceptions about plague were associated with these intentions.

  16. Perceptions and Reactions with Regard to Pneumonic Plague

    PubMed Central

    Amlôt, Richard; Rogers, M. Brooke; Hall, Ian; Leach, Steve; Simpson, John; Wessely, Simon

    2010-01-01

    We assessed perceptions and likely reactions of 1,005 UK adults to a hypothetical terrorist attack involving pneumonic plague. Likely compliance with official recommendations ranged from good (98% would take antimicrobial drugs) to poor (76% would visit a treatment center). Perceptions about plague were associated with these intentions. PMID:20031056

  17. Bronchoalveolar lavage in HIV infected patients with interstitial pneumonitis.

    PubMed Central

    de Blic, J; Blanche, S; Danel, C; Le Bourgeois, M; Caniglia, M; Scheinmann, P

    1989-01-01

    The value of taking microbiological and cytological specimens by flexible bronchoscopy and bronchoalveolar lavage under local anaesthesia was assessed on 43 occasions in 35 HIV infected children, aged 3 months to 16 years, with interstitial pneumonitis. In acute interstitial pneumonitis (n = 22, 26 specimens from bronchoalveolar lavages) the microbiological yield was 73%, Pneumocystis carinii being the commonest infective agent (n = 14). P carinii pneumonia was found only in children with deficient antigen induced lymphocyte proliferative responses who had not been treated with long term prophylactic co-trimoxazole. In contrast, in 13 children with chronic interstitial pneumonitis that was consistent with a diagnosis of pulmonary lymphoid hyperplasia who underwent bronchoalveolar lavage on 17 occasions, there were two isolates of cytomegalovirus and one of adenovirus, but P carinii was not found. Ten of the 13 children had normal antigen induced lymphocyte proliferative responses. Useful cytological data were also gleaned from bronchoalveolar lavage specimens. Lymphocytosis was significantly higher in pulmonary lymphoid hyperplasia (36(SD 11)%) than in P carinii pneumonia (24(19)%) whereas the percentage of polymorphonuclear neutrophils was significantly lower (3(2)% compared with 12(13)%). Flexible bronchoscopy with bronchoalveolar lavage is safe even in young infants and should reduce the necessity for open lung biopsy in the management of HIV infected children with interstitial pneumonitis. PMID:2817943

  18. Distractibility and hypersensitivity. Two behavior factors in elementary school children.

    PubMed

    Victor, J B; Halverson, C F

    1975-01-01

    The present paper reports on the development of a modified problem checklist for use in normal samples of elementary school children. The two factors, Hypersensitivity and Distractibility, replicated over male and female samples. Hypersensitivity showed a significant grade effect, with a decrease between the first and second grade for both boys and girls. In contrast, boys scored higher than girls on Distractibility and there were no grade differences. Convergent validitiy data from peer judgments, in-class activity level, physical fitness measures, standardized achievement scores, and a comparison with another teacher judgment are presented. In addition, three Behavioral Problem Checklist (Quay & Peterson, 1967) dimensions, Conduct Problem, Personality Problem, and Inadequacy--Immaturity, were developed and their relationships to the independent measures, as well as to the new dimensions, are presented. The pattern of correlations of Distractibility was quite similar for boys and girls, with both being rated as Mean-Noisy by their peers. The findings for Hypersensitivity were somewhat weaker. Distractibility and Conduct Problem scores reflected a similar pattern of correlations with other variables; in a like manner, Hypersensitivity and Personality Problem scores reflected a similar pattern of correlations with other variables. Distractibility was related to an increased activity level and Hypersensitivity was related to a decreased activity level in young boys. The total number of behavior problems was related to a decrease in activity level for young girls. Older Distractible and Hypersensitive girls showed different patterns of activity level. It is proposed that problem behavior is more complex for older children and that Distractibility may be less influenced by the usual socialization process of school than is Hypersensitivity and may have some congenital antecedents.

  19. 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.

  20. Jaundice induced by stanozolol hypersensitivity

    PubMed Central

    Slater, S. D.; Davidson, J. F.; Patrick, R. S.

    1976-01-01

    A 66-year-old male patient developed jaundice after 7 months of treatment with the anabolic steroid, stanozolol. When the drug was withdrawn he made a full and uneventful recovery. A liver biopsy showed the histology of a hypersensitivity reaction. This is believed to be the first time jaundice has been recorded with stanozolol therapy and the first time a hypersensitivity-type jaundice has been recorded with any anabolic steroid. ImagesFig. 2Fig. 3 PMID:1273017

  1. Drug hypersensitivity in Phramongkutklao Hospital.

    PubMed

    Sangasapasviliya, Atik; Prakongwong, Tharatip; Ayuthaya, Pinyapat Kanechorn Na; Ayuthaya, Rajyani Kanechaun Na

    2010-11-01

    To evaluate the prevalence of drug hypersensitivity, clinical manifestations, type of drugs involved, severity, and patients demographic data. A cross-sectional descriptive study. The study was performed from January 1st, 2008 to December 31th, 2008 at Phramongkutklao Hospital. Data were collected from Pharmaceutical Department, Dermatology Unit, Department of Medicine including adverse events reported by pharmacists. All records of in-patients and out-patients including gender, age, causative drugs, type of drug hypersensitivity and severity of hypersensitivity were collected. A total of 140 patients who had drug hypersensitivity were recorded. The most common drug hypersensitivity was due to antimicrobial agents which penicillin group was the most frequently involved. Of 61 patients (43.57%), 27 (19.28%) received anti-inflammatory and muscle relaxant drugs and 18 (12.85%) had drugs acting on the central nervous system. The most common manifestration of drug allergy was maculopapular rash (34.99%), followed by nonspecific erythrematous rash (16.42%), fixed drug eruption (9.28%) and Stevens-Johnson syndrome (8.57%), respectively. Majority (80.71%) of drug hypersensitivity was mild in severity. Moderate, severe and lethal hypersensitivity accounted for 8.51%, 10.0%, 0.71% respectively. Female were 51.77% while 48.22% were male. The mean age was 47.0 years (ranged from 8-100 years). There were 57 (40.71%) patients over 50 years of age and 103 (73.57%) patients had taken more than one medication. Antimicrobial agents were the common cause while maculopapular rash was the most frequent clinical manifestation of drug hypersensitivity.

  2. 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

  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. 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.

  5. Risk factors in interstitial pneumonitis following allogenic bone marrow transplantation

    SciTech Connect

    Pino Y Torres, J.L.; Bross, D.S.; Lam, W.C.; Wharam, M.D.; Santos, G.W.; Order, S.E.

    1982-08-01

    Total body irradiation is part of the preparatory regimen for allogeneic bone marrow transplantation because of its cytotoxic and immunosuppressive properties. A major toxicity of bone marrow transplantation has been interstitial pneumonitis, which may be, in part, related to the lung irradiation. One hundred and sixty-one consecutive patients receiving allogeneic bone marrow transplantation for leukemia and aplastic anemia at Johns Hopkins Hospital (1968-1979) were retrospectively studied. The present study demonstrated that lung shielding to 600 rad maximum in single dose total body irradiation, fractionation of total body irradiation in comparison to single dose total body irradiation, and absence of graft versus host disease in the leukemia patients, each reduced the risk of interstitial pneumonitis. Total body irradiation significantly reduced the leukemia recurrence rate and/or the failure of remission induction.

  6. [Acute lupus pneumonitis--case report and literature review].

    PubMed

    Starczewska, Małgorzata H; Wawrzyńska, Liliana; Opoka, Lucyna; Małek, Grzegorz; Wieliczko, Monika; Amatuszkiewicz-Rowińska, Joanna; Szturmowicz, Monika

    2013-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that is characterized by its chronic course and the involvement of many organs and systems. The most common abnormality in the respiratory system of SLE patients is lupus pleuritis. Less common is parenchymal involvement, which may present as acute lupus pneumonitis (ALP) or chronic interstitial lung disease. Other possible pulmonary manifestations of SLE include pulmonary embolism, diffuse alveolar haemorrhage, acute reversible hypoxaemia, and shrinking lung syndrome. We present the case report of a young woman with previously diagnosed membranous glomerulonephritis with nephrotic syndrome and antiphospholipid syndrome, who was admitted with marked of shortness of breath. The diagnostic process, including imaging studies and laboratory tests, enabled us to confirm a diagnosis of ALP. After initiation of treatment with high doses of methyloprednisolone, nearly complete remission of pulmonary changes was observed. We also perform a literature review regarding acute lupus pneumonitis.

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

    PubMed

    Sarkar, Supriya; Saha, Kaushik

    2012-07-01

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

  8. 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.

  9. Biomarkers for Radiation Pneumonitis Using Noninvasive Molecular Imaging.

    PubMed

    Medhora, Meetha; Haworth, Steven; Liu, Yu; Narayanan, Jayashree; Gao, Feng; Zhao, Ming; Audi, Said; Jacobs, Elizabeth R; Fish, Brian L; Clough, Anne V

    2016-08-01

    Our goal is to develop minimally invasive biomarkers for predicting radiation-induced lung injury before symptoms develop. Currently, there are no biomarkers that can predict radiation pneumonitis. Radiation damage to the whole lung is a serious risk in nuclear accidents or in radiologic terrorism. Our previous studies have shown that a single dose of 15 Gy of x-rays to the thorax causes severe pneumonitis in rats by 6-8 wk. We have also developed a mitigator for radiation pneumonitis and fibrosis that can be started as late as 5 wk after radiation. We used 2 functional SPECT probes in vivo in irradiated rat lungs. Regional pulmonary perfusion was measured by injection of (99m)Tc-macroaggregated albumin. Perfused volume was determined by comparing the volume of distribution of (99m)Tc-macroaggregated albumin to the anatomic lung volume obtained by small-animal CT. A second probe, (99m)Tc-labeled Duramycin, which binds to apoptotic cells, was used to measure pulmonary cell death in the same rat model. The perfused volume of lung was decreased by about 25% at 1, 2, and 3 wk after receipt of 15 Gy, and (99m)Tc-Duramycin uptake was more than doubled at 2 and 3 wk. There was no change in body weight, breathing rate, or lung histology between irradiated and nonirradiated rats at these times. Pulmonary vascular resistance and vascular permeability measured in isolated perfused lungs ex vivo increased at 2 wk after 15 Gy of irradiation. Our results suggest that SPECT biomarkers have the potential to predict radiation injury to the lungs before substantial functional or histologic damage is observed. Early prediction of radiation pneumonitis in time to initiate mitigation will benefit those exposed to radiation in the context of therapy, accidents, or terrorism. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  10. Biomarkers for radiation pneumonitis using non-invasive molecular imaging

    PubMed Central

    Medhora, Meetha; Haworth, Steven; Liu, Yu; Narayanan, Jayashree; Gao, Feng; Zhao, Ming; Audi, Said; Jacobs, Elizabeth R.; Fish, Brian L.; Clough, Anne V.

    2016-01-01

    Rationale Our goal is to develop minimally-invasive biomarkers for predicting radiation-induced lung injury before symptoms develop. Currently there are no biomarkers that can predict radiation pneumonitis. Radiation damage to the whole lung is a serious risk in nuclear accidents or in case of radiological terrorism. Our previous studies have shown a single dose of 15 Gy X-rays to the thorax causes severe pneumonitis in rats by 6–8 weeks. We have also developed a mitigator for radiation pneumonitis and fibrosis that can be started as late as 5 weeks after radiation. Methods We used two functional single photon emission computed tomography (SPECT) probes in vivo in irradiated rat lungs. Regional pulmonary perfusion was measured by injection of technetium labeled macroaggregated albumin (99mTc-MAA). Perfused volume was determined by comparing the volume of distribution of 99mTc-MAA to the anatomical lung volume obtained by micro-CT. A second probe, technetium labeled duramycin that binds to apoptotic cells, was used to measure pulmonary cell death in the same rat model. Results Perfused volume of lung was decreased by ~25% at 1, 2 and 3 weeks after 15 Gy and 99mTc-duramycin uptake was more than doubled at 2 and 3 weeks. There was no change in body weight, breathing rate or lung histology between irradiated and non-irradiated rats at these times. Pulmonary vascular resistance and vascular permeability measured in isolated perfused lungs ex vivo increased at 2 weeks after 15 Gy. Principal conclusions Our results suggest the potential for SPECT biomarkers for predicting radiation injury to the lungs before substantial functional or histological damage is observed. Early prediction of radiation pneumonitis will benefit those receiving radiation in the context of therapy, accidents or terrorism in time to initiate mitigation. PMID:27033892

  11. Pneumonitis associated with occult heartworm disease in dogs.

    PubMed

    Calvert, C A; Losonsky, J M

    1985-05-15

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

  12. A guinea pig model of bovine pneumonic pasteurellosis.

    PubMed Central

    Morck, D W; Costerton, J W; Bolingbroke, D O; Ceri, H; Boyd, N D; Olson, M E

    1990-01-01

    The induction of pneumonic pasteurellosis in guinea pigs (Cavia porcellus) was examined. Specific pathogen free male guinea pigs were anesthetized and a tracheostomy performed to introduce 10(5), 10(4) or 10(3) Pasteurella haemolytica-A1 into the left principal bronchus. The surgical site was closed with tissue adhesive and staples and the animals were monitored for signs of respiratory tract infection. Within 24 hours after inoculation they became depressed, anorectic, pyretic and dyspneic. Fibrinous pleuropneumonia with prominent areas of necrosis and hemorrhage was present. Pericardial effusion was a frequent finding. There was infiltration of the pleura and alveoli with degenerate heterophils and macrophages, a hyperplastic mesothelium and fibrin exudation on the pleura and within alveoli. Hemorrhage, congestion, consolidation, edema and fibrin exudation were prominent in the hilar region of the lungs. Bacterial colonies were evident in all airways. More bacteria were recovered from infected lungs than were inoculated (p less than 0.05) indicating P. haemolytica was actively multiplying in the lungs. Hematological and clinical chemistry data were consistent with fibrinous pneumonia, however, blood cultures were positive for P. haemolytica in 61% (11/18) of animals sampled. Examination of pneumonic pasteurellosis in guinea pigs may be useful in studying pathogenetic and pathological features applicable to bovine pneumonic pasteurellosis (shipping fever pneumonia). Images Fig. 1. Fig. 2. Fig. 4. Fig. 5. Fig. 7. Fig. 8. Fig. 9. PMID:2306663

  13. Protective effect of corticosteroids on radiation pneumonitis in mice

    SciTech Connect

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

    1988-01-01

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

  14. Pharmacogenetics of hypersensitivity drug reactions.

    PubMed

    Negrini, Simone; Becquemont, Laurent

    2017-04-01

    Adverse drug reactions are a significant cause of morbidity and mortality and represent a major burden on the healthcare system. Some of those reactions are immunologically mediated (hypersensitivity reactions) and can be clinically subdivided into two categories: immediate reactions (IgE-related) and delayed reactions (T-cell-mediated). Delayed hypersensitivity reactions include both systemic syndromes and organ-specific toxicities and can be triggered by a wide range of chemically diverse drugs. Recent studies have demonstrated a strong genetic association between human leukocyte antigen alleles and susceptibility to delayed drug hypersensitivity. Most notable examples include human leukocyte antigen (HLA)-B*57:01 allele and abacavir hypersensitivity syndrome or HLA-B*15:02 and HLA-B*58:01 alleles related to severe cutaneous reactions induced by carbamazepine and allopurinol, respectively. This review aims to explore our current understanding in the field of pharmacogenomics of HLA-associated drug hypersensitivities and its translation into clinical practice for predicting adverse drug reactions. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  15. Adding Ipsilateral V{sub 20} and V{sub 30} to Conventional Dosimetric Constraints Predicts Radiation Pneumonitis in Stage IIIA-B NSCLC Treated With Combined-Modality Therapy

    SciTech Connect

    Ramella, Sara; Trodella, Lucio; Mineo, Tommaso Claudio; Pompeo, Eugenio; Stimato, Gerardina; Gaudino, Diego; Valentini, Vincenzo; Cellini, Francesco; Ciresa, Marzia; Fiore, Michele; Piermattei, Angelo; Russo, Patrizia; Cesario, Alfredo; D'Angelillo, Rolando M.

    2010-01-15

    Purpose: To determine lung dosimetric constraints that correlate with radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional radiation therapy and concurrent chemotherapy. Methods and Materials: Between June 2002 and December 2006, 97 patients with locally advanced non-small-cell lung cancer were treated with concomitant radiochemotherapy. All patients underwent complete three-dimensional treatment planning (including dose-volume histograms), and patients were treated only if the percentage of total lung volume exceeding 20 Gy (V{sub 20}) and 30 Gy (V{sub 30}), and mean lung dose (MLD) had not exceeded the constraints of 31%, 18%, and 20 Gy, respectively. The total and ipsilateral lung dose-volume histogram parameters, planning target volume, and total dose delivered were analyzed and correlated with pneumonitis incidence. Results: If dose constraints to the total lung were respected, the most statistically significant factors predicting pneumonitis were the percentage of ipsilateral lung volume exceeding 20 Gy (V{sub 20}ipsi), percentage of ipsilateral lung volume exceeding 30 Gy (V{sub 30}ipsi), and planning target volume. These parameters divided the patients into low- and high-risk groups: if V{sub 20}ipsi was 52% or lower, the risk of pneumonitis was 9%, and if V{sub 20}ipsi was greater than 52%, the risk of pneumonitis was 46%; if V{sub 30}ipsi was 39% or lower, the risk of pneumonitis was 8%, and if V{sub 30}ipsi was greater than 39%, the risk of pneumonitis was 38%. Actuarial curves of the development of pneumonitis of Grade 2 or higher stratified by V{sub 20}ipsi and V{sub 30}ipsi were created. Conclusions: The correlation between pneumonitis and dosimetric constraints has been validated. Adding V{sub 20}ipsi and V{sub 30}ipsi to the classical total lung constraints could reduce pulmonary toxicity in concurrent chemoradiation treatment. V{sub 20}ipsi and V{sub 30}ipsi are important if the V{sub 20} to the total lung, V

  16. Immunological Mechanisms of Drug Hypersensitivity.

    PubMed

    Meng, Xiaoli; Ariza, Adriana; Waddington, James; Park, Kevin; Naisbitt, Dean

    2016-01-01

    Drug hypersensitivity reactions (DHRs) are adverse drug reactions that may be divided into several categories; namely pharmacologic intolerance, idiosyncratic reactions, pseudo-allergic reactions and allergic reactions. Drug allergic reactions are those DHRs that are mediated by either antibodies or drug-specific T cells. They vary in terms of severity, time-to-onset of clinical manifestations and target organ. Skin is most commonly implicated in drug hypersensitivity reactions; however, it is now apparent that reactions targeting internal organs fall under the definition of drug hypersensitivity. Multiple hypotheses have been proposed to explain the diverse immune mechanisms involved and the heterogeneous clinical presentation. The discovery of human leukocyte antigen (HLA) risk alleles for some DHRs has provided insights in the pathogenesis of these reactions. In this review we summarize immune cells involved in DHRs, discuss the possible immunological mechanisms of DHRs, with an emphasis on the IgE-mediated immediate reactions and T cell-dependent delayed type reactions.

  17. Cockroach hypersensitivity in asthmatic patients.

    PubMed

    Pola, J; Valdivieso, R; Zapata, C; Moneo, I; Duce, F; Larrad, L; Losada, E

    1988-01-01

    Hypersensitivity to cockroach antigen has been recognized as an important cause of perennial allergic rhinitis and asthma. To assess the frequency of cockroach hypersensitivity in our country, 150 asthmatic atopic subjects were studied using skin testing and in vitro assays for cockroach-specific IgE antibodies (Oriental and German cockroaches). Twenty-two of 61 patients who had a positive history of cockroach exposure had positive skin tests, and only 3 of 89 patients who had no history of exposure had positive skin reactions. Of 25 patients with positive skin tests, 23 showed specific IgE antibodies against oriental and German cockroaches using RAST and EIA techniques. In summary, approximately 15% of asthmatic atopics in Madrid area are sensitive to cockroaches (positive skin test + specific IgE antibodies). These results indicate that cockroach hypersensitivity should be considered in every patient with perennial asthma.

  18. 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.

  19. Tetanus immunisation in hypersensitive individuals.

    PubMed

    Williams, A N; Kabuubi, J B L; Owen, J P; Wells, J

    2002-06-01

    We report on a case of an officer cadet who was inadvertently allowed to commence training with a history suggestive of hypersensitivity to tetanus immunisation and who, eventually, successfully underwent a graduated immunisation regimen. This case combines a search for good evidence with the extraordinary complexities of military medical management and the law. It is a lesson in all three.

  20. 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

  1. Levofloxacin Cures Experimental Pneumonic Plague in African Green Monkeys

    PubMed Central

    McDonald, Jacob D.; Brasel, Trevor L.; Barr, Edward B.; Gigliotti, Andrew P.; Koster, Frederick

    2011-01-01

    Background Yersinia pestis, the agent of plague, is considered a potential bioweapon due to rapid lethality when delivered as an aerosol. Levofloxacin was tested for primary pneumonic plague treatment in a nonhuman primate model mimicking human disease. Methods and Results Twenty-four African Green monkeys (AGMs, Chlorocebus aethiops) were challenged via head-only aerosol inhalation with 3–145 (mean = 65) 50% lethal (LD50) doses of Y. pestis strain CO92. Telemetered body temperature >39°C initiated intravenous infusions to seven 5% dextrose controls or 17 levofloxacin treated animals. Levofloxacin was administered as a “humanized” dose regimen of alternating 8 mg/kg and 2 mg/kg 30-min infusions every 24-h, continuing until animal death or 20 total infusions, followed by 14 days of observation. Fever appeared at 53–165 h and radiographs found multilobar pneumonia in all exposed animals. All control animals died of severe pneumonic plague within five days of aerosol exposure. All 16 animals infused with levofloxacin for 10 days survived. Levofloxacin treatment abolished bacteremia within 24 h in animals with confirmed pre-infusion bacteremia, and reduced tachypnea and leukocytosis but not fever during the first 2 days of infusions. Conclusion Levofloxacin cures established pneumonic plague when treatment is initiated after the onset of fever in the lethal aerosol-challenged AGM nonhuman primate model, and can be considered for treatment of other forms of plague. Levofloxacin may also be considered for primary presumptive-use, multi-agent antibiotic in bioterrorism events prior to identification of the pathogen. PMID:21347450

  2. Central hypersensitivity in chronic musculoskeletal pain.

    PubMed

    Curatolo, Michele; Arendt-Nielsen, Lars

    2015-05-01

    Clinical research has consistently detected alteration in central pain processing leading to hypersensitivity. Most methods used in humans are reliable and have face validity to detect widespread central hypersensitivity. However, construct validity is difficult to investigate due to lack of gold standards. Reference values in the pain-free population have been generated, but need replication. Research on pain biomarkers that reflect specific central hypersensitivity processes is warranted. Few studies have analyzed the prognostic value of central hypersensitivity. Most medications acting at central level and some non-pharmacological approaches, including psychological interventions, are likely to attenuate central hypersensitivity.

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

    SciTech Connect

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

    1987-12-01

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

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

    PubMed Central

    Abraham, Albin; Karakurum, Ali

    2013-01-01

    Interstitial pneumonitis as an adverse effect of mesalamine therapy is a rare but potentially serious complication. Patients typically have a mild disease course with no documented cases of respiratory failure in published literature. Given its variable latent period and non-specific signs and symptoms, it may be difficult to diagnose. We present the case of a 65-year-old man who presented with symptoms of fever, shortness of breath and a non-productive cough, 2 weeks after initiation of therapy with mesalamine. His hospital course was complicated by acute respiratory failure requiring intubation and mechanical ventilation. Radiographic studies revealed bilateral lower lobe infiltrates and bronchosopy with bronchoalveolar lavage and transbronchial biopsy were consistent with a diagnosis of drug-induced interstitial pneumonitis. The aim of this paper is to highlight the importance of considering a diagnosis of mesalamine-induced lung injury in patients presenting with respiratory symptoms while on mesalamine therapy and to review relevant literature. PMID:23964037

  5. Extrinsic allergic alveolitis (hypersensitivity pneumonitis) caused by Sphingobacterium spiritivorum from the water reservoir of a steam iron.

    PubMed

    Kämpfer, Peter; Engelhart, S; Rolke, M; Sennekamp, J

    2005-09-01

    A case of extrinsic allergic alveolitis (EAA) caused by Sphingobacterium spiritivorum is described. The symptoms were associated with the use of a steam iron. The water reservoir was heavily contaminated with S. spiritivorum (10(6) CFU ml(-1)). This is the first report of S. spiritivorum as a causative agent of EAA.

  6. Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy.

    PubMed

    Naidoo, Jarushka; Wang, Xuan; Woo, Kaitlin M; Iyriboz, Tunc; Halpenny, Darragh; Cunningham, Jane; Chaft, Jamie E; Segal, Neil H; Callahan, Margaret K; Lesokhin, Alexander M; Rosenberg, Jonathan; Voss, Martin H; Rudin, Charles M; Rizvi, Hira; Hou, Xue; Rodriguez, Katherine; Albano, Melanie; Gordon, Ruth-Ann; Leduc, Charles; Rekhtman, Natasha; Harris, Bianca; Menzies, Alexander M; Guminski, Alexander D; Carlino, Matteo S; Kong, Benjamin Y; Wolchok, Jedd D; Postow, Michael A; Long, Georgina V; Hellmann, Matthew D

    2017-03-01

    Purpose Pneumonitis is an uncommon but potentially fatal toxicity of anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Clinical, radiologic, and pathologic features are poorly described. Methods Patients who received anti-PD-1/PD-L1 monotherapy or in combination with anti-cytotoxic T-cell lymphocyte-4 mAb were identified at two institutions (Memorial Sloan Kettering Cancer Center: advanced solid cancers, 2009 to 2014, and Melanoma Institute of Australia: melanomas only, 2013 to 2015). Pneumonitis was diagnosed by the treating investigator; cases with confirmed malignant lung infiltration or infection were excluded. Clinical, radiologic, and pathologic features of pneumonitis were collected. Associations among pneumonitis incidence, therapy received, and underlying malignancy were examined with Fisher's exact test as were associations between pneumonitis features and outcomes. Results Of 915 patients who received anti-PD-1/PD-L1 mAbs, pneumonitis developed in 43 (5%; 95% CI, 3% to 6%; Memorial Sloan Kettering Cancer Center, 27 of 578 [5%]; Melanoma Institute of Australia, 16 of 337 [5%]). Time to onset of pneumonitis ranged from 9 days to 19.2 months. The incidence of pneumonitis was higher with combination immunotherapy versus monotherapy (19 of 199 [10%] v 24 of 716 [3%]; P < .01). Incidence was similar in patients with melanoma and non-small-cell lung cancer (overall, 26 of 532 [5%] v nine of 209 [4%]; monotherapy, 15 of 417 v five of 152 [ P = 1.0]; combination, 11 of 115 v four of 57 [ P = .78]). Seventy-two percent (31 of 43) of cases were grade 1 to 2, and 86% (37 of 43) improved/resolved with drug holding/immunosuppression. Five patients worsened clinically and died during the course of pneumonitis treatment; proximal cause of death was pneumonitis (n = 1), infection related to immunosuppression (n = 3), or progressive cancer (n = 1). Radiologic and pathologic features of pneumonitis were diverse. Conclusion

  7. 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

  8. Ibuprofen-induced hypersensitivity syndrome.

    PubMed

    Nanau, Radu M; Neuman, Manuela G

    2010-06-01

    Ibuprofen is a widely used antipyretic and analgesic nonsteroidal antiinflammatory drug (NSAID). With the aging of the population, there will be a significant increase in the prevalence of painful degenerative and inflammatory rheumatic conditions. This increase likely will lead to a parallel increase in the use of NSAIDs, including ibuprofen. The primary effect of the NSAIDs is to inhibit cyclooxygenase (prostaglandin synthase), thereby impairing the ultimate transformation of arachidonic acid to prostaglandins, prostacyclin, and thromboxanes. Although in the majority of cases it is safe, this NSAID, ibuprofen, can produce an unpredictable, idiosyncratic, type B reaction that may pose a major concern in clinical practice. Type B reactions are known to occur in susceptible individuals. The true hypersensitivity reaction (HSR) is a systemic disease defined by the triad of fever, rash, and internal organ involvement that starts 1 day to 12 weeks after the initiation of therapy. HSR has limited the therapeutic use of many drugs, including ibuprofen. Hypersensitivity syndrome associated with ibuprofen is a host-dependent drug reaction that is idiosyncratic in nature. This reaction likely is caused by a combination of metabolic and immunologic factors. Immune mediated components, such as T-cell and their products cytokines and chemokines, can exacerbate cellular responses and create complex pathways that lead to a variety of clinical manifestations. Our review presents an ibuprofen-induced clinical manifestation of hypersensitivity syndrome and the necessity of wisely monitoring the patients clinically and by laboratory investigations when prescribing this drug.

  9. Nevirapine patch testing in Thai human immunodeficiency virus infected patients with nevirapine drug hypersensitivity.

    PubMed

    Prasertvit, Piyatida; Chareonyingwattana, Angkana; Wattanakrai, Penpun

    2017-08-06

    Antiretroviral drug hypersensitivity in HIV patients is common. Publications have shown that Abacavir (ABC) patch testing is useful in confirming ABC hypersensitivity in 24-50% of cases with a 100% sensitivity of HLA-B*5701 in patch test positive cases. However, Nevirapine (NVP) patch testing has not been reported. (1) To evaluate the usefulness and safety of NVP patch testing in Thai HIV patients with NVP hypersensitivity. (2) To assess the correlation of positive patch tests with HLA-B*3505. Patients were classified into two groups: (1) study group of 20 HIV NVP hypersensitivity patients and (2) control group of 15 volunteers without NVP hypersensitivity. Both groups were patch tested with purified and commercialized form of NVP in various vehicles. Two HIV patients with NVP hypersensitivity were patch test positive. All controls tested negative. Three HIV patients were positive for HLA-B*3505 and the two patients with positive patch testing were both HLA-B*3505 positive. NVP patch testing in Thai HIV patients is safe and can be used to help confirm the association between NVP and hypersensitivity skin reactions. NVP patch test results significantly correlated with HLA-B*3505. The sensitivity of HLA-B*3505 for positive patch test was 100%. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. 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.

  11. Safety and efficacy of substituting nedaplatin after carboplatin hypersensitivity reactions in gynecologic malignancies.

    PubMed

    Michikami, Hiroo; Minaguchi, Takeo; Ochi, Hiroyuki; Onuki, Mamiko; Okada, Satoshi; Matsumoto, Koji; Satoh, Toyomi; Oki, Akinori; Yoshikawa, Hiroyuki

    2013-01-01

    Repeated treatment with carboplatin increases the incidence of hypersensitivity reactions. Current managements for carboplatin hypersensitivity reactions involve premedication, desensitization, and replacing agents. However, preventive effects for recurrent reactions by the former two methods are still limited, and substituting non-platinum agent can attenuate efficacy against platinum-sensitive diseases. The aim of this study was to evaluate the safety and efficacy of substituting nedaplatin, another platinum compound, as a strategy to deal with carboplatin hypersensitivity reactions in gynecologic cancers. Patients who experienced carboplatin hypersensitivity reactions and subsequently switched to nedaplatin between 2001 and 2009 were identified through our database. The incidence and severity of nedaplatin hypersensitivity were examined. Response to nedaplatin therapy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) and serum CA-125 levels.   Forty-six of 570 patients (8.1%) experienced carboplatin hypersensitivity reactions, and the increased cycle numbers of carboplatin-based regimens correlated with the high incidence of hypersensitivity (≤6, 0.9% vs ≥7, 19.2%). Of these 46 patients, 38 subsequently switched to nedaplatin-based regimens (ovarian, tubal or peritoneal carcinoma, 30; endometrial carcinoma, 6; cervical carcinoma, 2). Three of the 38 patients (7.9%) eventually developed hypersensitivity against nedaplatin, and all their reactions were grade 2. The response rate to nedaplatin therapy among 32 evaluable patients was 31.3%. Replacing carboplatin with nedaplatin provided a safe and efficacious approach to manage carboplatin hypersensitivity. To the authors' knowledge, this study is the first to indicate the usefulness of nedaplatin after carboplatin hypersensitivity reactions. Further evaluations are warranted to confirm our finding. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan

  12. Low rate of cetuximab hypersensitivity reactions in Northeast Tennessee: An Appalachian effect?

    PubMed

    Adams, C Brooke; Street, D Sierra; Crass, Melanie; Bossaer, John B

    2016-12-01

    Cetuximab is a monoclonal antibody with a known risk of hypersensitivity reactions. Early studies showed hypersensitivity reaction rates of 3%, but there appears to be a higher incidence in the southeastern United States. To confirm the findings from nearby institutions that cetuximab-associated hypersensitivity reactions occur in approximately 20% of patients in the southeastern United States. A retrospective chart review was conducted at Johnson City Medical Center in Johnson City, Tennessee. Each patient's first infusion was analyzed for hypersensitivity reaction, as well as for demographic information such as allergy and smoking history, pre-medications, and malignancy type. Data from the first infusion of cetuximab were collected for a total of 71 patients with various malignancies. The overall rate of grade 3 or higher hypersensitivity reaction was 1.4%, and total rate of hypersensitivity reaction was 8.5%. These findings more closely correlate to the early clinical trials and package insert. Both severe (p = 0.001) and any-grade (p = 0.002) hypersensitivity reaction occurred less frequently in one Southeastern Appalachian medical center compared to academic medical centers directly to the east and west. Patients in southern Appalachia may be less likely to develop cetuximab hypersensitivity reactions compared to surrounding areas in the Southeastern U.S. These results lend support to the theory that exposure to lonestar ticks (Amblyomma americanum) may be responsible for the development of IgE antibodies to cetuximab that cause hypersensitivity reactions. The development of quick and reliable bedside predictors of cetuximab hypersensitivity reactions may aid clinicians considering the use of cetuximab. © The Author(s) 2015.

  13. Flux change in basophil membrane is not the main pathogenesis for hypersensitivity

    PubMed Central

    Wiwanitkit, Viroj

    2007-01-01

    The oxidation process is one of the most important natural processes. Oxidative change in hypersensitivity is believed to be an important process in the pathogenesis. However, the clear explanation on the transmembrane flux change of basophil and its correlation to hypersensitivity pathogenesis has never been reported. Here, the author determines the transmembrane oxidation flux in basophil. The simulation test to determine the oxidation flux change based on nanomedicine technique is used. Of interest, no change of flux can be detected. Therefore, this work can support the finding that the oxidation flux change is not an important part in the pathogenesis of basophil-related hypersensitivity. PMID:18203432

  14. Dietary hypersensitivity in cats and dogs.

    PubMed

    Mandigers, Paul; German, Alexander J

    2010-10-01

    Adverse reactions to food or dietary hypersensitivity are frequently seen problems in companion animal medicine and may be difficult to differentiate from inflammatory bowel disease (IBD). Dietary hypersensitivity can be divided into two subgroups: immunological and nonimmunological problems. Non-immunological problems can be subdivided into food intolerance, food poisoning, and dietary indiscretion. The immunological group can be subdivided into true food allergy (IgE mediated) and anaphylaxis (non-IgE mediated). This article gives an outline of what dietary hypersensitivity is, and more specifically food allergy and how to deal with patients with possible dietary hypersensitivity.

  15. Clonal analysis of the T-cell response of mice to herpes simplex virus: correlation between lymphokine production in vitro and the induction of delayed-type hypersensitivity and antiviral activity in vivo.

    PubMed

    Seid, M; Leung, K N; Pye, C; Phelan, J; Nash, A A; Godfrey, H P

    1987-01-01

    The properties of two morphologically distinct L3T4+, Lyt2- "helper" T-cell clones specific for herpes simplex virus were investigated. Both of the clones produced IL-3 and interferon, but neither produced IL-2. Clone D6.6 produced macrophage agglutinating factor, a fibronectin-like lymphokine, and also a delayed hypersensitivity (DH) response when injected locally into syngeneic mice. Despite the presence of a DH producing clone and a non-DH producing clone, both were able to reduce the local virus titre to an equivalent degree. It is suggested that this protective activity is associated with the production of interferon-gamma. The significance of these results to mechanisms of protection against herpes simplex virus in vivo is discussed.

  16. 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

  17. 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.

  18. Desensitizing Agent Reduces Dentin Hypersensitivity During Ultrasonic Scaling: A Pilot Study

    PubMed Central

    Suda, Tomonari; Akiyama, Toshiharu; Takano, Takuya; Gokyu, Misa; Sudo, Takeaki; Khemwong, Thatawee; Izumi, Yuichi

    2015-01-01

    Background Dentin hypersensitivity can interfere with optimal periodontal care by dentists and patients. The pain associated with dentin hypersensitivity during ultrasonic scaling is intolerable for patient and interferes with the procedure, particularly during supportive periodontal therapy (SPT) for patients with gingival recession. Aim This study proposed to evaluate the desensitizing effect of the oxalic acid agent on pain caused by dentin hypersensitivity during ultrasonic scaling. Materials and Methods This study involved 12 patients who were incorporated in SPT program and complained of dentin hypersensitivity during ultrasonic scaling. We examined the availability of the oxalic acid agent to compare the degree of pain during ultrasonic scaling with or without the application of the dentin hypersensitivity agent. Evaluation of effects on dentin hypersensitivity was determined by a questionnaire and visual analog scale (VAS) pain scores after ultrasonic scaling. The statistical analysis was performed using the paired Student t-test and Spearman rank correlation coefficient. Results The desensitizing agent reduced the mean VAS pain score from 69.33 ± 16.02 at baseline to 26.08 ± 27.99 after application. The questionnaire revealed that >80% patients were satisfied and requested the application of the desensitizing agent for future ultrasonic scaling sessions. Conclusion This study shows that the application of the oxalic acid agent considerably reduces pain associated with dentin hypersensitivity experienced during ultrasonic scaling. This pain control treatment may improve patient participation and treatment efficiency. PMID:26501012

  19. Natural rubber latex hypersensitivity with skin prick test in operating room personnel.

    PubMed

    Nabavizadeh, Seyed Hessamedin; Anushiravani, Amir; Amin, Reza

    2009-12-01

    Hypersensitivity reactions to natural rubber latex have increased recently, especially among people with high exposure to latex allergens. Hypersensitivity reactions to latex are related to many conditions like occupational asthma. Our study was performed to determine the prevalence of hypersensitivity to natural rubber latex and potential food cross reactions in operation room personnel in Shiraz hospitals. In this cross-sectional, descriptive study, 580 operation room personnel filled out our questionnaire which included data about their personal history, symptoms of latex hypersensitivity, and other related allergies such as food hypersensitivity. An informed consent was obtained and skin prick tests were performed for natural rubber latex and potential food cross reactions (kiwi, banana, and potato). The obtained data were analyzed by SPSS and Chi-square test. 104 (17.9%) of the operating room personnel showed positive latex skin tests. We revealed a significant correlation between those with positive skin tests to latex with atopia, urthicaria, and food hypersensitivity. The prevalence did not vary by sex, age, education, surgical and non-surgical gloves users, or history of contact dermatitis. Latex hypersensitivity is common among operation room personnel. Evaluation of symptoms and prediction of future diseases necessitate screening tests in individuals at risk.

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

    PubMed

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

    2016-11-01

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

  1. 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.

  2. 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.

  3. Reaginic hypersensitivity in ulcerative colitis

    PubMed Central

    Jewell, D. P.; Truelove, S. C.

    1972-01-01

    Reaginic hypersensitivity in ulcerative colitis has been investigated in respect of a hypersensitivity to the cow's milk proteins and the frequency of atopic asthma, hay fever, and eczema. Intradermal tests were frequently positive, especially to casein, but the results did not differ from those found in healthy individuals and in groups of patients with Crohn's disease, hypolactasia, and the irritable colon syndrome. No circulating IgE-specific antibodies to the milk proteins were found. An increased frequency of atopic diseases was found in patients suffering from ulcerative colitis (15·7%) and Crohn's disease (13·3%) compared with the findings in a control group (1·2%). It is concluded that, if an allergy to milk proteins is a factor in the pathogenesis of ulcerative colitis, it is not mediated by reaginic antibodies. It is possible, however, that the frequent occurrence of atopy indicates a susceptibility to develop reaginic responses even though this mechanism does not apply to the milk proteins. PMID:4646293

  4. Anticonvulsant hypersensitivity syndrome treated with intravenous immunoglobulin.

    PubMed

    Dredge, David C; Parsons, Elizabeth C; Carter, Lindsay P; Staley, Kevin J

    2010-07-01

    Anticonvulsant hypersensitivity syndrome is a severe, potentially life-threatening, reaction to the aromatic anticonvulsant medications. Reported here is a case of anticonvulsant hypersensitivity syndrome secondary to phenobarbital in a 2-year-old boy; he responded to drug withdrawal, corticosteroids, and intravenous immunoglobulin. The literature regarding treatment of this syndrome is reviewed.

  5. 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.

  6. Metal hypersensitivity: can it mimic infection?

    PubMed

    Anand, Ashish; McGlynn, Fred; Jiranek, William

    2009-08-01

    Metal hypersensitivity leading onto hardware rejection is reported as a rare phenomenon. If not suspected, it can be a harrowing experience for the patient because it can lead to a seemingly never-ending cycle of tests and procedures. This case highlights the fact that although metal hypersensitivity is rare, it should be included in the differential once infection has been excluded.

  7. Cytomegalovirus reactivation in drug induced hypersensitivity syndrome.

    PubMed

    Mathuram, Alice J; George, Renu E

    2014-06-01

    Drug induced hypersensitivity syndrome has been reported to a variety of drugs. Reactivation of herpes viruses is associated with relapse of symptoms even as late as five weeks after stopping the inciting drug. We report here a case of drug hypersensitivity with CMV reactivation which was treated successfully.

  8. Age factor relevant to the development of radiation pneumonitis in radiotherapy of lung cancer

    SciTech Connect

    Koga, K.; Kusumoto, S.; Watanabe, K.; Nishikawa, K.; Harada, K.; Ebihara, H.

    1988-02-01

    The significance of age factor for the development of radiation pneumonitis is evaluated in 62 patients with lung cancer between 1977 and 1985. The younger group consists of those less than 70 years old and the elderly group of those 70 years old or more. Radiation doses ranged from 1.5 to 2 Gy, 3 to 5 times per week, therefore the delivered doses were converted to nominal single doses (rets dose). Severe radiation pneumonitis was more often observed in the elderly than in the younger regardless of radiation field size and chemotherapy (n.s.). The onset of radiation pneumonitis occurred earlier in a field size of 90 sq cm or more than in that of less than 90 sq cm in both age groups; there was no significant difference between the two age groups in each field size. The pneumonitis was more frequently noted with increasing rets dose in both age groups (n.s.) regardless of field size and chemotherapy. It is concluded that there is no significant difference in the development of radiation pneumonitis between the younger group and the elderly group, but the pneumonitis is inclined to be more severe in the latter.

  9. 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.

  10. Allergic or Hypersensitivity Reactions to Orthopaedic Implants.

    PubMed

    Roberts, Timothy T; Haines, Colin M; Uhl, Richard L

    2017-10-01

    Allergic or hypersensitivity reactions to orthopaedic implants can pose diagnostic and therapeutic challenges. Although 10% to 15% of the population exhibits cutaneous sensitivity to metals, deep-tissue reactions to metal implants are comparatively rare. Nevertheless, the link between cutaneous sensitivity and clinically relevant deep-tissue reactions is unclear. Most reactions to orthopaedic devices are type IV, or delayed-type hypersensitivity reactions. The most commonly implicated allergens are nickel, cobalt, and chromium; however, reactions to nonmetal compounds, such as polymethyl methacrylate, antibiotic spacers, and suture materials, have also been reported. Symptoms of hypersensitivity to implants are nonspecific and include pain, swelling, stiffness, and localized skin reactions. Following arthroplasty, internal fixation, or implantation of similarly allergenic devices, the persistence or early reappearance of inflammatory symptoms should raise suspicions for hypersensitivity. However, hypersensitivity is a diagnosis of exclusion. Infection, as well as aseptic loosening, particulate synovitis, instability, and other causes of failure must first be eliminated.

  11. 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.

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

    PubMed Central

    Pang, Zhaofei; Ding, Nan; Dong, Wei; Ni, Yang; Zhang, Tiehong; Qu, Xiao

    2017-01-01

    Background In the eighth TNM staging system proposal, lung cancer with part or complete obstructive pneumonitis/atelectasis was classified to T2 category, and dividing lines of T category were changed. We conducted this study to search prognostic effect of preoperative obstructive pneumonitis/atelectasis and its comparison with tumor size. Methods We collected clinical characteristics, preoperative hematological indicators, follow-up information of 1,313 lung cancer patients. Chi-square test was used to search relationship between obstruction pneumonitis/atelectasis and other factors. Kaplan-Meier (K-M) curves and cox regression methods were used for survival analysis. Results Preoperative obstructive pneumonitis/atelectasis indicated shorter OS (HR: 1.308; 95% CI: 1.058–1.619) and RFS (HR: 1.276; 95% CI: 1.032–1.579) as an independent factor. In comparison with tumor size, we found patients with obstructive pneumonitis/atelectasis and T1 size tumor had similar prognosis to those with T2 size but without obstructive pneumonitis/atelectasis, and OS, RFS of patients with obstructive pneumonitis/atelectasis and T2 size were significantly shorter than those with T2 tumor size but without obstructive pneumonitis/atelectasis, while similar to patients with T3 tumor size but without obstructive pneumonitis/atelectasis according to division by the eighth edition. We also found obstructive pneumonitis/atelectasis was significantly related to higher neutrophil (P<0.001), platelet (P<0.001), monocyte (P<0.001), NLR (P<0.001), PLR (P=0.002), ESR (P<0.001) and lower LMR (P<0.001). Conclusions Preoperative obstructive pneumonitis/atelectasis predicted poor survival independently in non-small cell lung cancer (NSCLC). And we suggested which T staging group the patients with obstructive pneumonitis/atelectasis would be divided to should depend on tumor size in the eighth TNM staging system. PMID:28449485

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

    PubMed

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

    2017-03-01

    In the eighth TNM staging system proposal, lung cancer with part or complete obstructive pneumonitis/atelectasis was classified to T2 category, and dividing lines of T category were changed. We conducted this study to search prognostic effect of preoperative obstructive pneumonitis/atelectasis and its comparison with tumor size. We collected clinical characteristics, preoperative hematological indicators, follow-up information of 1,313 lung cancer patients. Chi-square test was used to search relationship between obstruction pneumonitis/atelectasis and other factors. Kaplan-Meier (K-M) curves and cox regression methods were used for survival analysis. Preoperative obstructive pneumonitis/atelectasis indicated shorter OS (HR: 1.308; 95% CI: 1.058-1.619) and RFS (HR: 1.276; 95% CI: 1.032-1.579) as an independent factor. In comparison with tumor size, we found patients with obstructive pneumonitis/atelectasis and T1 size tumor had similar prognosis to those with T2 size but without obstructive pneumonitis/atelectasis, and OS, RFS of patients with obstructive pneumonitis/atelectasis and T2 size were significantly shorter than those with T2 tumor size but without obstructive pneumonitis/atelectasis, while similar to patients with T3 tumor size but without obstructive pneumonitis/atelectasis according to division by the eighth edition. We also found obstructive pneumonitis/atelectasis was significantly related to higher neutrophil (P<0.001), platelet (P<0.001), monocyte (P<0.001), NLR (P<0.001), PLR (P=0.002), ESR (P<0.001) and lower LMR (P<0.001). Preoperative obstructive pneumonitis/atelectasis predicted poor survival independently in non-small cell lung cancer (NSCLC). And we suggested which T staging group the patients with obstructive pneumonitis/atelectasis would be divided to should depend on tumor size in the eighth TNM staging system.

  14. The Bronchoalveolar Lavage Pattern in Radiation Pneumonitis Secondary to Radiotherapy for Breast Cancer

    PubMed Central

    Toma, Claudia Lucia; Serbescu, Aneta; Alexe, Mihai; Cervis, Luminita; Ionita, Diana; Bogdan, Miron Alexandru

    2010-01-01

    capacity for carbon monoxide was seen in both groups on pulmonary function tests. The lung volumes were normal in all patients. Conclusions: Lymphocytic alveolitis was the marker of radiation pneumonitis in all patients. The degree of the inflammatory reaction of the lungs was correlated with the presence of symptoms. The lymphocytic alveolitis consisted mainly of T lymphocytes, with a predominance of CD4 subset in both groups, but the CD4/CD8 ratio remained mostly into normal range. PMID:21977166

  15. Clinical heterogeneity of drug hypersensitivity.

    PubMed

    Roujeau, Jean-Claude

    2005-04-15

    Skin is the most frequent target of drug reactions that are reported, may be because they are easily detected. Most (probably more than 90%) are related to drug hypersensitivity, i.e. an individually tailored, unexpected effect mediated by a drug specific activation of the immune response. The clinical presentation of "drug eruptions" is highly variable, from the most common transient and benign erythema that occurs 6-9 days after the introduction of a new drug in 1 to 3 % of users to the most severe forms, that fortunately affect less than 1/10,000 users. Even though there are some overlapping or unclassifiable cases, it is important for clinicians to recognize and categorize severe cutaneous adverse reactions/SCAR (bullous fixed drug eruptions/bFDE, acute generalized exanthematous pustulosis/AGEP, drug reaction with eosinophilia and systemic symptoms/DRESS, Stevens-Johnson syndrome/SJS, toxic epidermal necrolysis/TEN). First they must suspect rapidly that an unusual eruption with high fever and severe constitutional symptoms is caused by a medication and not by an infection. Second they have to look for involvement of organs that differ according to the type of reaction. Third they can determine a prognosis, the mortality rate being virtually 0 for bFDE, 5% for AGEP, 10% for "hypersensitivity syndrome"/DRESS and 25% for SJS or TEN. In addition if some medications are "usual suspects" for all types (e.g. anticonvulsants), some other are more specific of a given pattern (pristinamycine, hydroxychloroquine, diltiazem for AGEP, minocycline for DRESS, anti-infectious sulfonamides, allopurinol for epidermal necrolysis). The "phenotypic" diversity of the final expression drug reactions can be explained by the engagement of a variety of cytokines and inflammatory cells and by regulatory mechanisms. For example, memory cytotoxic T-Cells are key effectors in both localized blisters of bFDE and in extensive blisters of epidermal necrolysis.

  16. 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

  17. Hypersensitivity reactions in patients receiving hemodialysis.

    PubMed

    Butani, Lavjay; Calogiuri, Gianfranco

    2017-06-01

    To describe hypersensitivity reactions in patients receiving maintenance hemodialysis. PubMed search of articles published during the past 30 years with an emphasis on publications in the past decade. Case reports and review articles describing hypersensitivity reactions in the context of hemodialysis. Pharmacologic agents are the most common identifiable cause of hypersensitivity reactions in patients receiving hemodialysis. These include iron, erythropoietin, and heparin, which can cause anaphylactic or pseudoallergic reactions, and topical antibiotics and anesthetics, which lead to delayed-type hypersensitivity reactions. Many hypersensitivity reactions are triggered by complement activation and increased bradykinin resulting from contact system activation, especially in the context of angiotensin-converting enzyme inhibitor use. Several alternative pharmacologic preparations and dialyzer membranes are available, such that once an etiology for the reaction is established, recurrences can be prevented without affecting the quality of care provided to patients. Although hypersensitivity reactions are uncommon in patients receiving hemodialysis, they can be life-threatening. Moreover, considering the large prevalence of the end-stage renal disease population, the implications of such reactions are enormous. Most reactions are pseudoallergic and not mediated by immunoglobulin E. The multiplicity of potential exposures and the complexity of the environment to which patients on dialysis are exposed make it challenging to identify the precise cause of these reactions. Great diligence is needed to investigate hypersensitivity reactions to avoid recurrence in this high-risk population. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. Metal hypersensitivity in total joint arthroplasty.

    PubMed

    Pinson, Michelle L; Coop, Christopher A; Webb, Charles N

    2014-08-01

    To review the clinical manifestations, testing methods, and treatment options for hypersensitivity reactions to total joint arthroplasty procedures. Studies were identified using MEDLINE and reference lists of key articles. Randomized controlled trials were selected when available. Systematic reviews and meta-analyses of peer-reviewed literature were included, as were case series and observational studies of clinical interest. Total joint arthroplasty procedures are increasing, as are the hypersensitivity reactions to these implants. Evidence is not conclusive as to whether metal joint implants increase metal sensitivity or whether metal sensitivity leads to prosthesis failure. Currently, patch testing is still the most widely used method for determining metal hypersensitivity; however, there are no standardized commercial panels specific for total joint replacements available currently. In vitro testing has shown comparable results in some studies, but its use in the clinical setting may be limited by the cost and need for specialized laboratories. Hypersensitivity testing is generally recommended before surgery for patients with a reported history of metal sensitivity. In cases of metal hypersensitivity-related joint failure, surgical revision ultimately may be required. Knowledge about joint replacement hypersensitivity reactions becomes vital because the approach to the evaluation depends on appropriate testing to guide recommendations for future arthroplasty procedures. Evaluation of hypersensitivity reactions after total joint arthroplasty requires a systematic approach, including a careful history, targeted evaluation with skin testing, and in vitro studies. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  19. The prognosis of wheat hypersensitivity in children.

    PubMed

    Kotaniemi-Syrjänen, Anne; Palosuo, Kati; Jartti, Tuomas; Kuitunen, Mikael; Pelkonen, Anna S; Mäkelä, Mika J

    2010-03-01

    The study was aimed to determine the natural history of wheat hypersensitivity, to define risk factors for persistent wheat hypersensitivity, and to evaluate the development of respiratory allergy in children with wheat hypersensitivity. The development and subsequent disappearance of wheat hypersensitivity, clinical findings, skin prick test (SPT) reactivity, and the development of allergic rhinoconjunctivitis and asthma were charted retrospectively in 28 children with wheat hypersensitivity proven by the open oral challenge at the median age of 21 months (range 6 to 75 months). Appearance of skin symptoms during the diagnostic wheat challenge was related to SPT-positive wheat hypersensitivity, while the appearance of gastrointestinal symptoms alone was associated with SPT-negative wheat hypersensitivity (p=0.002). Wheat was tolerated by 59%, 69%, 84%, and 96%, by age 4, 6, 10, and 16, respectively. Sensitization to gliadin with a SPT wheal of >or=5 mm at the time of the diagnostic challenge was associated with a slower course of recovery from wheat hypersensitivity (p=0.019), and a SPT wheal of >or=3 mm to gliadin at any time was associated with the development of asthma (p=0.022). SPT reactivity to wheat was associated with later SPT reactivity to birch pollen (p=0.001), and the development of allergic rhinoconjunctivitis (p=0.001). In conclusion, almost all children with wheat hypersensitivity can tolerate wheat by adolescence. Sensitization to gliadin is associated with a slower achievement of tolerance and an increased risk of asthma. Copyright (c) 2009 John Wiley & Sons A/S

  20. Longitudinal analysis of antibody profiles against plakins in severe drug eruptions: emphasis on correlation with tissue damage in drug-induced hypersensitivity syndrome and drug reaction with eosinophilia and systemic symptoms.

    PubMed

    Takehara, A; Aoyama, Y; Kurosawa, M; Shirafuji, Y; Umemura, H; Kamiya, K; Ushigome, Y; Kano, Y; Shiohara, T; Iwatsuki, K

    2016-11-01

    The evidence for severe drug eruption as a trigger for autoimmune disease has recently increased. No information is available on how tissue damage in severe drug eruptions can induce autoimmune responses. To investigate whether the generation of autoantibodies (autoAbs) against plakin family proteins could be the cause or result of tissue damage in patients with severe drug eruptions and whether the generation of autoAbs could be prevented by systemic corticosteroids during the acute stage. We retrospectively analysed alterations of serum levels of autoAbs against plakin family proteins in patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) during the acute stage and long after resolution over a period of more than 10 years. AutoAbs against plakin family proteins were detected in patients with either SJS/TEN or DiHS/DRESS regardless of the epidermal damage in the acute stage, and were sustained even long after resolution in DiHS/DRESS, indicating that those autoAbs are neither the cause nor the consequence of epidermal damage, at least in DiHS/DRESS. Severe liver damage and noncorticosteroid therapy during the early and acute stages of DiHS/DRESS were associated with the subsequent generation of these autoAbs. These autoAbs are neither necessarily the cause nor the result of epidermal damage in DiHS/DRESS, because the presence of these autoAbs was not restricted to patients with SJS/TEN but was also observed in those with DiHS/DRESS, which is characterized by lack of epidermal damage. Severe liver damage and/or immune responses that could be prevented by corticosteroids in the acute stage of DiHS/DRESS are among the causal factors contributing to the generation of autoimmune responses. © 2016 British Association of Dermatologists.

  1. Hypersensitivity to contrast media and dyes.

    PubMed

    Brockow, Knut; Sánchez-Borges, Mario

    2014-08-01

    This article updates current knowledge on hypersensitivity reactions to diagnostic contrast media and dyes. After application of a single iodinated radiocontrast medium (RCM), gadolinium-based contrast medium, fluorescein, or a blue dye, a hypersensitivity reaction is not a common finding; however, because of the high and still increasing frequency of those procedures, patients who have experienced severe reactions are nevertheless frequently encountered in allergy departments. Evidence on allergologic testing and management is best for iodinated RCM, limited for blue dyes, and insufficient for fluorescein. Skin tests can be helpful in the diagnosis of patients with hypersensitivity reactions to these compounds.

  2. Hypothesis on how to measure electromagnetic hypersensitivity.

    PubMed

    Tuengler, Andreas; von Klitzing, Lebrecht

    2013-09-01

    Electromagnetic hypersensitivity (EHS) is an ill-defined term to describe the fact that people who experience health symptoms in the vicinity of electromagnetic fields (EMFs) regard them as causal for their complaints. Up to now most scientists assume a psychological cause for the suffering of electromagnetic hypersensitive individuals. This paper addresses reasons why most provocation studies could not find any association between EMF exposure and EHS and presents a hypothesis on diagnosis and differentiation of this condition. Simultaneous recordings of heart rate variability, microcirculation and electric skin potentials are used for classification of EHS. Thus, it could be possible to distinguish "genuine" electromagnetic hypersensitive individuals from those who suffer from other conditions.

  3. 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

  4. Risk factors contributing to the development of carboplatin-related delayed hypersensitivity reactions in Japanese patients with gynecologic cancers.

    PubMed

    Sugimoto, Hiroko; Iwamoto, Takuya; Murashima, Yukiko; Tabata, Tsutomu; Sagawa, Norimasa; Okuda, Masahiro

    2011-02-01

    The rate of hypersensitivity reactions in patients receiving carboplatin (CBDCA) has been reported to increase after multiple doses of the agent. However, risk factors for these onsets have not been well described. In this study, we investigated the contribution of the reported risk factors to the onset of CBDCA-related delayed hypersensitivity reactions. We reviewed the records of gynecologic cancer patients receiving CBDCA of more than 7 cycles in Mie University Hospital from March 2006 to July 2009. The patients were divided into two groups on the basis of whether hypersensitivity reactions developed (13 patients) or not (43 patients). Thereafter, the potential influences of the patients' characteristics on the development of CBDCA-related delayed hypersensitivity reactions were explored using logistic regression analyses. The median CBDCA-free interval (10 months) in patients with hypersensitivity reactions was significantly higher than that (3 months) in patients without hypersensitivity reactions. Logistic regression analyses revealed a CBDCA-free interval >13 months (odds ratio 22.2, 95% confidence interval 2.57-192, p < 0.01) and a maximum dose of CBDCA > 650 mg (odds ratio 9.52, 95% confidence interval 1.04-93.9; p < 0.05) were significantly correlated with the incidence of CBDCA-related delayed hypersensitivity reactions. Careful attention should be paid to the onset of delayed hypersensitivity reactions for recurrent gynecologic cancer patients receiving CBDCA > 650 mg after an interval of more than 13 months from the previous CBDCA administration.

  5. 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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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

    PubMed Central

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

    2015-01-01

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

  7. FcγRIIa ligation induces platelet hypersensitivity to thrombotic stimuli.

    PubMed

    Berlacher, Mark D; Vieth, Joshua A; Heflin, Brittany C; Gay, Steven R; Antczak, Adam J; Tasma, Brian E; Boardman, Holly J; Singh, Navinderjit; Montel, Angela H; Kahaleh, M Bashar; Worth, Randall G

    2013-01-01

    Platelets are known for their important role in hemostasis, however their significance in other functions, including inflammation and infection, are becoming more apparent. Patients with systemic lupus erythematosus (SLE) are known to have circulating IgG complexes in their blood and are highly susceptible to thrombotic events. Because platelets express a single receptor for IgG, we tested the hypothesis that ligation of this receptor (FcγRIIa) induces platelet hypersensitivity to thrombotic stimuli. Platelets from SLE patients were considerably more sensitive to thrombin compared to healthy volunteers, and this correlated with elevated levels of surface IgG on SLE platelets. To test whether FcγRIIa ligation stimulated thrombin hypersensitivity, platelets from healthy volunteers were incubated with buffer or heat-aggregated IgG, then stimulated with increasing concentrations of thrombin. Interestingly, heat-aggregated IgG-stimulated platelets, but not buffer-treated platelets, were hypersensitive to thrombin, and hypersensitivity was blocked by an anti-FcγRIIa monoclonal antibody (mAb). Thrombin hypersensitivity was not due to changes in thrombin receptor expression (GPIbα or PAR1) but is dependent on activation of shared signaling molecules. These observations suggest that ligation of platelet FcγRIIa by IgG complexes induces a hypersensitive state whereby small changes in thrombotic stimuli may result in platelet activation and subsequent vascular complications such as transient ischemic attacks or stroke.

  8. 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.

  9. Oxaliplatin hypersensitivity: evaluation, implications of skin testing, and desensitization.

    PubMed

    Wong, Johnson T; Ling, Morris; Patil, Sarita; Banerji, Aleena; Long, Aidan

    2014-01-01

    Oxaliplatin hypersensitivity (OXS) presents a challenge in the treatment of oxaliplatin-sensitive malignancies. To analyze patient characteristics of patients with OXS, skin test results, and desensitization outcomes to optimize management. Over 5 years, 48 patients with OXS were referred to the allergy/immunology unit at Massachusetts General Hospital. Their clinical reaction patterns were analyzed. Immediate hypersensitivity skin testing was used for risk stratification, and drug desensitizations were performed by using 3 related continuous intravenous protocols that were chosen based on clinical history, skin test reactivity, and the patients' previous desensitization outcomes. OXS occurred in both sexes, with mostly gastrointestinal-related tumors. Hypersensitivity reaction (HSR) onset had occurred during any course of therapy (course nos. 1-28), with a median onset at course no. 8. HSR to oxaliplatin was similar to those observed with cisplatin and carboplatin, including cutaneous, cardiovascular, pulmonary, and gastrointestinal symptoms. However, neurologic symptoms, including tingling, and systemic symptoms, including fever and chills, occurred more often in patients with OXS. Unique to OXS, 2 patients developed drug-induced thrombocytopenia; 1 patients also developed drug-induced hemolytic anemia. Skin testing was positive for the majority of patients with OXS (27/46 [59%]) and correlated with a greater likelihood of developing an HSR during subsequent desensitizations. We safely performed 200 desensitizations in 48 patients with OXS. OXS is common with much similarity to other platin agents but also have distinct differences in the onset of hypersensitivity, sex, tumor type, drug-induced hemolytic anemia, and drug-induced thrombocytopenia. Skin testing was helpful for risk stratification. All of the desensitizations were completed successfully. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights

  10. 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.

  11. 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.

  12. [A case of MPO ANCA associated glomerulonephritis with interstitial pneumonitis complicated with lung tuberculosis and pericarditis].

    PubMed

    Takahashi, K; Suda, S; Takayama, M; Deguchi, F; Matsuda, O; Tachibana, K; Yoshimura, A

    2000-10-01

    The main target organs of myeloperoxidase (MPO) antineutrophil cytoplasmic antibodies (ANCA)-related disease are the kidney and lung. This report describes a 71-year-old man with rapidly progressive glomerulonephritis (RPGN) and interstitial pneumonitis associated with MPO ANCA. The patient was admitted to our hospital because of bloody sputum, low grade fever and appetite loss on October, 1998. He was diagnosed as having interstitial pneumonitis from the findings of chest X-ray and CT examinations. Moderate proteinuria and hematuria, renal dysfunction(serum creatinine: 5.6 mg/dl, BUN: 58.0 mg/dl) and positivity for MPO ANCA were noted. He was negative for anti-glomerular antibody and PR3-ANCA. Renal biopsy was performed and revealed crescentic glomerulonephritis without deposition of immunoglobulins. Therefore, the diagnosis of pauci immune type RPGN was made. Pulse therapy with methylprednisolone(1.0 g/day x 3 days) following oral administration of prednisolone (60 mg/day) found marked improvement of renal function maintenance and interstitial pneumonitis, respectively. However, he died because of lung tuberculosis and acute tuberculous pericarditis during treatment with prednisolone. In this case, MPO ANCA might have been directly associated with both RPGN and interstitial pneumonitis. Furthermore, chronic lung disease, such as interstitial pneumonitis, is important as a preceding disease of RPGN. MPO ANCA-related disease is more frequent in aged persons, therefore particular attention should be paid during their treatment with an immunosuppressant.

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

    PubMed

    Tamaki, Katsuyoshi; Okubo, Akihiko

    2015-01-21

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

  14. Pneumonic tularaemia: experience of 58 cases from 2000 to 2012 in Northern Finland.

    PubMed

    Väyrynen, Sara A; Saarela, Elina; Henry, Janne; Lahti, Sini; Harju, Terttu; Kauma, Heikki

    2017-10-01

    Pneumonic tularaemia is less common clinical form of tularaemia compared with the ulceroglandular form, with only a limited number of case reports and case series in Europe. In Finland, Northern Ostrobothnia is an endemic area of tularaemia with occasional seasonal outbreaks. In our study, a consecutive series of 58 pneumonic tularaemia cases diagnosed and treated in Oulu University Hospital in 2000-2012 were retrospectively analysed in terms of epidemiology, clinical course, and prognosis. The incidence of pneumonic tularaemia showed peaks in cycles of a few years and most cases were diagnosed in late summer or early autumn. Respiratory symptoms were absent in 47% of patients, and 7% had normal chest X-ray. The chest computed tomography (CT) was performed in 81% of patients, demonstrating variable findings associated with pneumonic tularaemia. Bronchoscopy was performed for 22 (38%) patients and four (18%) of these also proceeded into mediastinoscopy. Moreover, thoracoscopy was performed for one (2%) patient. Two (3%) patients were treated shortly in the intensive care unit (ICU) during their stay in hospital. No mortality was observed. Most cases of pneumonic tularaemia are diagnosed during the seasonal outbreaks. The lack of specific symptoms often complicates the diagnosis and leads to unnecessarily invasive examinations.

  15. Hypersensitivity reactions associated with endovascular devices.

    PubMed

    Honari, Golara; Ellis, Stephen G; Wilkoff, Bruce L; Aronica, Mark A; Svensson, Lars G; Taylor, James S

    2008-07-01

    Allergic reactions to endoprostheses are uncommon and reported in association with orthopaedic, dental, endovascular and other implanted devices. Hypersensitivity reactions to the biomaterials used in endovascular prostheses are among the infrequent reactions that may lead to local or systemic complications following cardiovascular therapeutic interventions. This article reviews potential immunotoxic effects of commonly used biomaterials. Reports of putative hypersensitivity reactions to endovascular devices, including coronary stents, perforated foramen occluders, pacemakers and implantable cardioverter defibrillators are also reviewed.

  16. 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

  17. Drug-hypersensitivity syndrome: diagnosis and treatment.

    PubMed

    Hamm, Rose L

    2011-12-01

    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.

  18. Chemotherapy and biotherapy-induced hypersensitivity reactions.

    PubMed

    Van Gerpen, Ruth

    2009-01-01

    Nearly all chemotherapy and biotherapy drugs used in cancer treatment today can cause hypersensitivity reactions. Certain groups of drugs frequently associated with these reactions include the asparaginases, taxanes, platinum compounds, epipodophyllotoxins, and the monoclonal antibodies. Recognizing and managing hypersensitivity reactions are critical when caring for patients receiving these drugs because the reactions are potentially life-threatening. A thorough understanding of the drugs is necessary to assist the nurse in prevention, early recognition, and timely management.

  19. Drug Induced Hypersensitivity and the HLA Complex

    PubMed Central

    Alfirevic, Ana; Pirmohamed, Munir

    2011-01-01

    Drug-induced hypersensitivity reactions are of major concern and present a burden for national healthcare systems due to their often severe nature, high rate of hospital admissions and high mortality. They manifest with a wide range of symptoms and signs, and can be initiated by a wide range of structurally diverse chemical compounds. The pathophysiological mechanisms underlying hypersensitivity reactions are not well understood, but it is thought that they are immune mediated. MHC region on Chromosome 6 contains many genes with immune function. Classical MHC molecules are highly polymorphic cell surface glycoproteins whose function is to present peptide antigens to T cells. In addition to conferring protection from some diseases, HLA alleles are also associated with an increased risk of other diseases, including drug-induced hypersensitivity. Pharmacogenetic approach to predict the risk of drug-induced hypersensitivity has been established for several drugs. We will discuss the progress of hypersensitivity pharmacogenetics over the last few years and focus on current efforts of the international community to develop consortia which aim to standardize disease phenotypes and to identify affected individuals through international collaborations. In addition, we will discuss the clinical utility of HLA typing as predictive or diagnostic testing for drug-induced hypersensitivity.

  20. Classification and pathophysiology of radiocontrast media hypersensitivity.

    PubMed

    Brockow, Knut; Ring, Johannes

    2010-01-01

    Hypersensitivity reactions to radiocontrast media (RCM) are unpredictable and are a concern for radiologists and cardiologists. Immediate hypersensitivity reactions manifest as anaphylaxis, and an allergic IgE-mediated mechanism has been continuously discussed for decades. Non-immediate reactions clinically are exanthemas resembling other drug-induced non-immediate hypersensitivities. During the past years, evidence is increasing that some of these reactions may be immunological. Repeated reactions after re-exposure, positive skin tests, and presence of specific IgE antibodies as well as positive basophil activation tests in some cases, and positive lymphocyte transformation or lymphocyte activation tests in others, indicate that a subgroup of both immediate and non-immediate reactions are of an allergic origin, although many questions remain unanswered. Recently reported cases highlight that pharmacological premedication is not safe to prevent RCM hypersensitivity in patients with previous severe reactions. These insights may have important consequences. A large multicenter study on the value of skin tests in RCM hypersensitivity concluded that skin testing is a useful tool for diagnosis of RCM allergy. It may have a role for the selection of a safe product in previous reactors, although confirmatory validation data is still scarce. In vitro tests to search for RCM-specific cell activation still are in development. In conclusion, recent data indicate that RCM hypersensitivity may have an allergic mechanism and that allergological testing is useful and may indicate tolerability. Copyright 2010 S. Karger AG, Basel.

  1. Hypersensitivity to biomedical implants: Prevention and diagnosis.

    PubMed

    Rosner, Gregory A; Fonacier, Luz S

    2017-05-01

    There has been growing interest in the potential for adverse immunologic reactions to metals in biomedical devices and increasing referrals for the evaluation and management of metal hypersensitivity reactions reported in orthopedic, cardiac, gynecologic, and dental implant devices. However, there are few studies that give evidence-based recommendations on how to evaluate this issue in our practices. We reviewed reasonable evidence and expert opinion on biomedical device hypersensitivity and published guidelines on pre- and postimplantation evaluation of delayed hypersensitivity reactions in patients suspected of possible metal hypersensitivity to biomedical devices. There is consensus that routine preimplantation evaluation in individuals with no history of adverse cutaneous reactions to metals or a history of implant-related adverse events is not necessary. However, patients with a history of metal hypersensitivity of a magnitude sufficient to cause concern for the patient or health care provider may benefit from evaluation by patch testing (PT) before device implantation. Patients after implantation and with chronic unexplained implant failure or with dermatitis may benefit from patch test evaluation after other causes, such as infection and biomechanical issues, are ruled out. However, a positive metal patch test result does not prove symptom causality, and the decision regarding implant revision can only be made after a thorough discussion among the patient, the allergist or dermatologist, and the orthopedic surgeon. Consensus guidelines for the evaluation of hypersensitivity to biomedical devices can be used by the practicing physician while awaiting for the results of further investigations.

  2. Esophageal hypersensitivity in noncardiac chest pain.

    PubMed

    Min, Yang Won; Rhee, Poong-Lyul

    2016-09-01

    Noncardiac chest pain (NCCP) is an often-encountered clinical problem. Although many patients suffer from persistent or recurrent chest pain, treatment remains a challenge owing to its various possible etiologies. Gastroesophageal reflux disease (GERD) is the most common cause of NCCP. In GERD-related NCCP, proton pump inhibitor treatment appears to be effective. However, the pathophysiology remains to be fully elucidated in NCCP patients without GERD. Treatment for non-GERD-related NCCP has been aimed at esophageal motility disorders and visceral hypersensitivity. As there is growing evidence that esophageal visceral hypersensitivity plays a role in NCCP, pain modulators have become the mainstay of therapy in patients with non-GERD-related NCCP. However, there is an unmet need for the treatment of esophageal hypersensitivity in NCCP due to modest evidence for the benefit of pain modulators, including antidepressants, in non-GERD-related NCCP. Recent studies have demonstrated that esophageal mast cell infiltration and impaired mucosal integrity are related to visceral hypersensitivity in patients with NCCP. Thus, esophageal mast cell stabilization and restoration of esophageal mucosal integrity could be considered potential therapeutic targets in selected NCCP patients with hypersensitivity. However, further observations are necessary to shed light on esophageal hypersensitivity in NCCP.

  3. Characteristics and Prognostic Impact of Pneumonitis during Systemic Anti-Cancer Therapy in Patients with Advanced Non-Small-Cell Lung Cancer

    PubMed Central

    Fujimoto, Daichi; Kato, Ryoji; Morimoto, Takeshi; Shimizu, Ryoko; Sato, Yuki; Kogo, Mariko; Ito, Jiro; Teraoka, Shunsuke; Nagata, Kazuma; Nakagawa, Atsushi; Otsuka, Kojiro; Tomii, Keisuke

    2016-01-01

    Background Data on characteristics, outcomes, and prognosis of advanced non-small-cell lung cancer (NSCLC) patients who develop pneumonitis during systemic anti-cancer therapy (pneumonitis) are currently lacking. Methods We conducted a retrospective cohort study of 910 consecutive patients diagnosed with advanced NSCLC between January 2004 and January 2014. Of these, 140 patients were excluded because they did not receive systemic anti-cancer therapy at this hospital. Results A total of 770 patients were included in the study, of whom 44 (6%) were diagnosed with pneumonitis. The mortality rate of pneumonitis was 36%. The incidence of pneumonitis was independently associated with pre-existing ILD (adjusted odds ratio, 2.99, P = 0.008), and survivors were significantly associated with younger age (P = 0.003) and radiographic non-acute interstitial pneumonia pattern (P = 0.004). In all patients, pneumonitis was identified as an independent predictor of overall survival (OS) (adjusted hazard ratio 1.53, 95% CI, 1.09–2.09, P = 0.015). Performance status was poor in 82% of survivors of pneumonitis; in 62% of survivors, the PS worsened after the pneumonitis improved. Additionally, 54% of survivors received no further systemic anti-cancer therapy after pneumonitis. The median survival time of survivors after pneumonitis was 3.5 months (95% CI, 2.3–7.2 months). Conclusions Our study indicated that 6% of patients with advanced NSCLC developed pneumonitis during systemic anti-cancer therapy. The early mortality rate of pneumonitis is high, and the survival and PS after pneumonitis is extremely poor. Additionally, pneumonitis has an adverse impact on the survival of patients with advanced NSCLC. These data should be considered for the management of pneumonitis, and we recommend that future work focuses on pneumonitis particularly to improve the survival of patients with advanced NSCLC. PMID:28006019

  4. Milestones in Progression of Primary Pneumonic Plague in Cynomolgus Macaques▿

    PubMed Central

    Koster, Frederick; Perlin, David S.; Park, Steven; Brasel, Trevor; Gigliotti, Andrew; Barr, Edward; Myers, Leslie; Layton, Robert C.; Sherwood, Robert; Lyons, C. R.

    2010-01-01

    Vaccines against primary pneumonic plague, a potential bioweapon, must be tested for efficacy in well-characterized nonhuman primate models. Telemetered cynomolgus macaques (Macaca fascicularis) were challenged by the aerosol route with doses equivalent to approximately 100 50% effective doses of Yersinia pestis strain CO92 and necropsied at 24-h intervals postexposure (p.e.). Data for telemetered heart rates, respiratory rates, and increases in the temperature greater than the diurnal baseline values identified the onset of the systemic response at 55 to 60 h p.e. in all animals observed for at least 70 h p.e. Bacteremia was detected at 72 h p.e. by a Yersinia 16S rRNA-specific quantitative reverse transcription-PCR and was detected later by the culture method at the time of moribund necropsy. By 72 h p.e. multilobar pneumonia with diffuse septal inflammation consistent with early bacteremia was established, and all lung tissues had a high bacterial burden. The levels of cytokines or chemokines in serum were not significantly elevated at any time, and only the interleukin-1β, CCL2, and CCL3 levels were elevated in lung tissue. Inhalational plague in the cynomolgus macaque inoculated by the aerosol route produces most clinical features of the human disease, and in addition the disease progression mimics the disease progression from the anti-inflammatory phase to the proinflammatory phase described for the murine model. Defined milestones of disease progression, particularly the onset of fever, tachypnea, and bacteremia, should be useful for evaluating the efficacy of candidate vaccines. PMID:20385751

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

    PubMed

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

    2017-01-01

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

  6. Cytomegalovirus pneumonitis complicated by a central peribronchial pattern of organising pneumonia.

    PubMed

    Cuadrado, Maria M; Ahmed, Asia; Carpenter, Ben; Brown, Jeremy S

    2017-01-01

    We present five cases of cytomegalovirus (CMV) pneumonitis occurring in patients after recent T cell deplete allogeneic stem cell transplantation (AlloHSCT). These cases were complicated by an organising pneumonia (during the recovery period) with a predominantly central peribronchial pattern. All patients presented with evidence of active CMV pneumonitis which was treated successfully with anti-viral therapy but was followed by persistent severe dyspnoea, cough and hypoxia. High resolution computed tomography (HRCT) imaging showed widespread central peribronchial consolidation with traction bronchiectasis. There was a marked clinical and physiological improvement after treatment with systemic corticosteroids. However, in all patients the lung function remained abnormal and in some cases imaging revealed a fibrosing lung disease. These cases represent a previously undescribed central peribronchial pattern of organising pneumonia complicating CMV pneumonitis that can result in chronic lung damage.

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

    PubMed

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

    2008-09-01

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

  8. PROSPECTIVE ASSESSMENT OF DOSIMETRIC/PHYSIOLOGIC-BASED MODELS FOR PREDICTING RADIATION PNEUMONITIS

    PubMed Central

    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.

    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 two cohorts of patients from Duke and the Netherlands Cancer Institute (NKI). Methods and Materials For the Duke cohort, 55 eligible patients treated between 1999-2005 on a prospective IRB-approved study to monitor RT-induced lung injury were analyzed. A similar group of patients treated at the NKI between 1996-2002 were identified. Patients believed to be at high and low risk for pneumonitis were defined based on: a) MLD; b) OpRP (sum of predicted perfusion reduction based on regional dose response curve); and c) 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 7/20 and 9/35, respectively; p=0.33 one tailed Fisher’s. Similarly, comparable rates for the NKI group are 4/21 and 6/44, respectively, p=0.41 one-tailed Fisher’s. Conclusion The prospective model is 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. PMID:17189069

  9. Interstitial pneumonitis associated with sirolimus in liver transplantation: a case report.

    PubMed

    Pérez, M J; Martín, R O; García, D M; Rey, J M Lozano; de la Cruz Lombardo, J; Rodrigo López, J M

    2007-12-01

    Sirolimus is a powerful immunosuppressive drug initially used in kidney transplant patients but now increasingly employed in recipients of other types of solid organ transplants, such as liver, heart, lung, or pancreas. Sirolimus is indicated for rescue therapy and to reduce the toxic side effects of calcineurin inhibitors. However, its use has been associated with an uncommon but important pulmonary toxicity. Reports have described interstitial pneumonitis, bronchiolitis obliterans, organizing pneumonia, and alveolar proteinosis. We present the case of a liver transplant patient with interstitial pneumonitis associated with sirolimus.

  10. 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.

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

    PubMed

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

    2016-06-23

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

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

    PubMed

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

    2012-01-01

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

  13. Successful treatment and prevention of murine Pneumocystis carinii pneumonitis with 4,4'-sulfonylbisformanilide.

    PubMed Central

    Hughes, W T; Smith, B L; Jacobus, D P

    1986-01-01

    Pneumocystis carinii pneumonitis was prevented in 0, 50, 100, and 100% of immunosuppressed rats given doses of 0.5, 5.0, 25.0, and 125.0 mg/kg (body weight) per day, respectively, of 4,4'-sulfonylbisformanilide (DFD). Therapeutic efficacy was demonstrated with DFD at 25.0 mg/kg per day, and when this dose was combined with trimethoprim, the combination was as effective as trimethoprim-sulfamethoxazole, which has been proven to be effective in the treatment of murine and human P. carinii pneumonitis. PMID:3487287

  14. The role of central hypersensitivity in the determination of intradiscal mechanical hyperalgesia in discogenic pain.

    PubMed

    Schliessbach, Juerg; Arendt-Nielsen, Lars; Heini, Paul; Curatolo, Michele

    2010-05-01

    The primary aim of the present study was to investigate whether there is a relationship between central hypersensitivity (assessed by pressure pain thresholds of uninjured tissues) and intradiscal pain threshold during discography. The secondary aim was to test the hypothesis that peripheral noxious stimulation dynamically modulates central hypersensitivity. Twenty-four patients with positive provocation discography were tested for central hypersensitivity by pressure algometry before and after the intervention with assessments of pressure pain detection and tolerance thresholds. Intradiscal pain threshold was assessed by measuring intradiscal pressure at the moment of pain provocation during discography. Correlation analyses between intradiscal pain threshold and pressure algometry were made. For the secondary aim, pressure algometry data before and after discography were compared. Significant correlation with intradiscal pain threshold was found for pressure pain detection threshold at the toe (regression coefficient: 0.03, P = 0.05) and pressure pain tolerance thresholds at the nonpainful point at the back (0.02, P = 0.024). Tolerance threshold at the toe was a significant predictor for intradiscal pain threshold only in multiple linear regression (0.036, P = 0.027). Detection as well as tolerance thresholds significantly decreased after discography at the painful and the nonpainful point at the back, but not at the toe. Central hypersensitivity may influence intradiscal pain threshold, but with a modest quantitative impact. The diagnostic value of provocation discography is therefore not substantially impaired. Regional, but not generalized central hypersensitivity is dynamically modulated by ongoing peripheral nociceptive input.

  15. CT Scan Findings of Probable Usual Interstitial Pneumonitis Have a High Predictive Value for Histologic Usual Interstitial Pneumonitis

    PubMed Central

    Chawla, Ashish; Peljto, Anna L.; Cool, Carlyne D.; Groshong, Steve D.; Talbert, Janet L.; McKean, David F.; Brown, Kevin K.; Fingerlin, Tasha E.; Schwarz, Marvin I.; Schwartz, David A.; Lynch, David A.

    2015-01-01

    BACKGROUND: The current usual interstitial pneumonitis (UIP)/idiopathic pulmonary fibrosis CT scan classification system excludes probable UIP as a diagnostic category. We sought to determine the predictive effect of probable UIP on CT scan on histology and the effect of the promoter polymorphism in MUC5B (rs35705950) on histologic and CT scan UIP diagnosis. METHODS: The cohort included 201 subjects with pulmonary fibrosis who had lung tissue samples obtained within 1 year of chest CT scan. UIP diagnosis on CT scan was categorized as inconsistent with, indeterminate, probable, or definite UIP by two to three pulmonary radiologists. Tissue slides were scored by two expert pulmonary pathologists. All subjects with available DNA (N = 200) were genotyped for rs35705950. RESULTS: The proportion of CT scan diagnoses were as follows: inconsistent with (69 of 201, 34.3%), indeterminate (72 of 201, 35.8%), probable (34 of 201, 16.9%), and definite (26 of 201, 12.9%) UIP. Subjects with probable UIP on CT scan were more likely to have histologic probable/definite UIP than subjects with indeterminate UIP on CT scan (82.4% [28 of 34] vs 54.2% [39 of 72]; P = .01). CT scan and microscopic honeycombing were not associated with each other (P = .76). The minor (T) allele of the MUC5B polymorphism was associated with concordant CT scan and histologic UIP diagnosis (P = .03). CONCLUSIONS: Probable UIP on CT scan is associated with a higher rate of histologic UIP than indeterminate UIP on CT scan suggesting that they are distinct groups and should not be combined into a single CT scan category as currently recommended by guidelines. CT scan and microscopic honeycombing may be dissimilar entities. The T allele at rs35705950 predicts a UIP diagnosis by both chest CT scan and histology. PMID:25317858

  16. Hypersensitivity reactions to dapsone: a systematic review.

    PubMed

    Lorenz, Maria; Wozel, Gottfried; Schmitt, Jochen

    2012-03-01

    Dapsone is widely used in the treatment of leprosy and several chronic inflammatory dermatological conditions. Hypersensitivity reactions to dapsone are potentially fatal adverse drug reactions with unknown prevalence and risk factors. We performed a systematic review covering all reported cases of hypersensitivity reactions, in order to systematically summarize the published evidence on prevalence, clinical course and fatality rate. Articles were identified through standardized search strategies. Included studies were reviewed for hypersensitivity characteristics and odds ratios were calculated in univariate and multivariate regression models to assess the risk factors for fatal outcome. A total of 114 articles (17 epidemiological studies, 97 case reports) totalling 336 patients with hypersensitivity reactions were included for analysis. From the epidemiological studies a total hypersensitivity reaction prevalence rate of 1.4% (95% confidence interval 1.2–1.7%) was determined. Mucosal involvement, hepatitis, higher age and disease occurrence in non-affluent countries were associated with higher risk of fatal outcome. Overall, the fatality rate was 9.9%.

  17. 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.

  18. 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

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

    SciTech Connect

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

    2013-02-01

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

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

    PubMed Central

    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.

    2012-01-01

    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. Yersina 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 LD50. Intranasal infection of mice with 15 LD50 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 of

  1. 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

  2. The Relationship between Grandiose and Vulnerable (Hypersensitive) Narcissism.

    PubMed

    Jauk, Emanuel; Weigle, Elena; Lehmann, Konrad; Benedek, Mathias; Neubauer, Aljoscha C

    2017-01-01

    Narcissistic grandiosity is characterized by overt expressions of feelings of superiority and entitlement, while narcissistic vulnerability reflects hypersensitivity and introversive self-absorbedness. Clinical evidence suggests that grandiosity is accompanied by vulnerable aspects, pointing to a common foundation. Subclinical personality research, however, views grandiose and vulnerable narcissism as independent traits. Grandiose narcissism displays substantial correlation with extraversion, while vulnerable narcissism correlates highly with introversion. We investigated if (1) controlling for intro-/extraversion might reveal a "common core" of grandiose and vulnerable narcissism, and if (2) the correlation between both aspects might be higher at higher levels of narcissism. Latent variable structural equation modeling and segmented regression analysis confirmed these hypotheses in a large non-clinical sample (N = 1,006). Interindividual differences in intro-/extraversion mask the common core of grandiose and vulnerable narcissism. The association between both aspects increases at high levels (upper 10%) of grandiose narcissism, which suggests a possible transition to clinically relevant (pathological) narcissism.

  3. 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

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

    PubMed

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

    2009-02-01

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

  5. 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.

  6. 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

  7. Chlamydia trachomatis pneumonitis in the C57BL/KsJ mouse: pathologic and immunologic features.

    PubMed

    Harrison, H R; Lee, S M; Lucas, D O

    1982-12-01

    Pneumonitis occurred in both normal and diabetic C57BL/KsJ mice, inoculated with a Chlamydia trachomatis strain isolated from a human infant . Animals were inoculated intranasally under light ether anesthesia. Control animals receiving carrier medium did not develop pulmonary disease. The pneumonitis was focal and involved interstitial and peribronchial structures. Pathological changes were most pronounced at 10 to 14 days after inoculation, but no animals died of their disease. The early cellular response was polymorphonuclear (4 to 6 days); this was followed by a predominantly mononuclear cell infiltrate. Immunopathological examination revealed immunoglobulin- and complement-bearing cells in a peribronchial distribution, corresponding to the mononuclear infiltrates seen by light microscopy. Infected animals seroconverted to C. trachomatis. Specific antichlamydial IgM antibody was detected at days 6 through 21 and higher titer IgG at days 10 through 28. Splenic lymphocyte stimulation responses to chlamydial antigen were observed at 10 and 21 days. C. trachomatis was cultured only from 6-day lung tissue. The histopathological and immunopathological features of the pneumonitis were similar in normal and diabetic mice. In addition, humoral and cellular immunoresponsiveness to chlamydial infection were not compromised in the diabetics. This animal model resembles human infant chlamydial pneumonitis in its pathological manifestations and may increase our understanding of the human disease.

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

    PubMed

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

    2010-09-01

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

  9. Utility of Respiratory Vaccination With Recombinant Subunit Vaccines for Protection Against Pneumonic Plague

    DTIC Science & Technology

    2002-01-01

    Immunity at mucosal sites can prevent pathogen infection of the host. A) oral poliovirus vaccine B) inhaled influenza vaccine C) kennel cough & Newcastle...Utility of respiratory vaccination with recombinant subunit vaccines for protection against pneumonic plague. Douglas S. Reed & Jennifer Smoll...2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Utility of respiratory vaccination with recombinant subunit vaccines for

  10. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. 113.71 Section 113.71 Animals and Animal Products ANIMAL AND PLANT HEALTH... prepared from chlamydia-bearing cell culture fluids or embryonated chicken eggs. Only Master Seed which has...

  11. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. 113.71 Section 113.71 Animals and Animal Products ANIMAL AND PLANT HEALTH... prepared from chlamydia-bearing cell culture fluids or embryonated chicken eggs. Only Master Seed which has...

  12. Assessing the potential to induce respiratory hypersensitivity.

    PubMed

    Holsapple, Michael P; Jones, David; Kawabata, Thomas T; Kimber, Ian; Sarlo, Kathy; Selgrade, MaryJane K; Shah, Jui; Woolhiser, Michael R

    2006-05-01

    Acute and repeat dose inhalation studies have been an important part of the safety assessment of drugs, chemicals, and other products throughout the world for many years. It is known that damage to the respiratory tract can be triggered either by nonspecific irritation or by specific immune-mediated pathogenesis, and it is acknowledged that traditional inhalation studies are not designed to address fully the impact of the latter. It is also recognized that different types of immune-mediated responses can be triggered by different classes of compounds and that some immune reactions in the lung are life threatening. As such, it is important to understand as fully as possible the basis for the immune-mediated damage to the lung in order to characterize adequately the risks of individual chemicals or proteins. It is against this background that a review of the methods used to assess the potential for immune-mediated respiratory hypersensitivity was conducted. The primary objectives of this review are to discuss appropriate methods for identifying and characterizing respiratory hypersensitivity hazards and risks; and to identify key data gaps and related research needs with respect to respiratory hypersensitivity testing. The following working definition of respiratory hypersensitivity was formulated: a hypersensitivity response in the respiratory tract precipitated by a specific immune response, mediated by multiple mechanisms, including IgE antibody. Because of the importance played by various classes of compounds, the subsequent sections of this review will consider protein-specific, chemical-specific, and drug-specific aspects of respiratory hypersensitivity.

  13. 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.

  14. Reversal of visceral and somatic hypersensitivity in a subset of hypersensitive rats by intracolonic lidocaine

    PubMed Central

    Zhou, QiQi; Price, Donald D.; Verne, G. Nicholas

    2010-01-01

    Chronic abdominal pain is a common gastrointestinal symptom experienced by patients. We have previously shown that IBS patients with visceral hypersensitivity also have evidence of thermal hypersensitivity of the hand and foot that is reversed by rectal lidocaine jelly. We have also recently developed an animal model of chronic visceral and somatic hypersensitivity in rats treated with intracolonic trinitrobenzene sulfonic acid (TNBS). The objective of the current study was to determine the effects of intracolonic lidocaine on visceral/somatic hypersensitivity in TNBS-treated rats. A total of 20 hypersensitive rats received either 20 mg intracolonic lidocaine (n = 10) or saline jelly (n = 10). In comparison to saline jelly, intracolonic lidocaine jelly reduced responses to nociceptive visceral/somatic stimuli in hypersensitive rats. The effects were present within 5–30 min after administration of lidocaine and lasted for 6 h. Lidocaine had no effects on recovered rats or control rats that had originally been treated with intracolonic saline instead of TNBS. Local anesthetic blockade of peripheral impulse input from the colon reduces both visceral and somatic hypersensitivity in TNBS-treated rats, similar to results in IBS patients. The results provide further evidence that visceral and secondary somatic hypersensitivity in a subset of TNBS-treated rats reflect central sensitization mechanisms maintained by tonic impulse input from the colon. This study evaluates the reversal of visceral/somatic hypersensitivity in a subset of TNBS-treated rats with intracolonic lidocaine. This animal model may be used in the future to study the mechanisms of local anesthetic agents applied to the gut to reduce visceral pain. PMID:18486344

  15. Delayed cutaneous manifestations of drug hypersensitivity.

    PubMed

    Bircher, Andreas J; Scherer, Kathrin

    2010-07-01

    Drugs may elicit a considerable variety of clinical signs, often affecting the skin and the mucous membranes. The most common are maculopapular exanthemas and urticaria, more rarely pustules, bullae vasculitic lesions, and lichenoid lesions may also be observed. Apart from the morphology, the chronology of the occurrence and the evolution of single skin lesions and exanthema are also paramount in the clinical diagnosis of cutaneous drug hypersensitivity. Often, the skin represents the only organ manifestation; however, it may be the herald for a systemic involvement of internal organs, such as in severe drug-induced hypersensitivity syndromes or anaphylaxis.

  16. 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

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

    PubMed Central

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

    2012-01-01

    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 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

  19. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. [Successful combination therapy of cyclosporine and steroids in two cases with interstitial pneumonitis associated with polymyositis].

    PubMed

    Ando, S; Kobayashi, S; Yamanaka, K; Takasaki, Y; Hashimoto, H

    1995-02-01

    Cyclosporine is an immunosuppressive agent which is well-established in the transplantation of organs including kidney, liver and bone marrow. It acts by inhibiting the production of interleukin 2, thereby blocking both the development of cytotoxic lymphocytes, and the proliferation of helper T cells. T cell-mediated muscle damage is thought to be important in the pathogenesis of polymyositis. And activated cytotoxic T cells are thought to play an important role of polymyositis/dermatomyositis with active pneumonitis. It is thereby likely that cyclosporine would be effective in the management of polymyositis with interstitial pneumonitis. We have used cyclosporine in two cases of corticosteroids resistant polymyositis associated with pneumonitis. The first case was admitted because of the relapse of polymyositis. She was partially responded by the high dose of steroid, but showed decreased %DLCO and increased AaDO2 during the therapy. And oral cyclosporine was given with steroid. Within two weeks, serum creatinine kinase level was reduced to normal range, and the improvement of pneumonitis was observed. The second case was admitted because of the flare of pneumonitis. She was treated with high dose of steroid with insufficient response. And cyclosporine was prescribed. Within two weeks of treatment, her symptom was relieved, and blood gas analysis showed an improvement of pulmonary function. And steroid could be tapered. In both cases, the initial dose of cyclosporine was 200 mg/day, and the optimal trough level was thought to be ranged 100 to 150 ng/ml. In the second case, renal dysfunction was observed but it was recovered by the reduction of the dose of cyclosporine. No other side effect was appeared.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

  2. 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

  3. 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

  4. Metal Hypersensitivity and Total Knee Arthroplasty.

    PubMed

    Lachiewicz, Paul F; Watters, Tyler Steven; Jacobs, Joshua J

    2016-02-01

    Metal hypersensitivity in patients with a total knee arthroplasty (TKA) is a controversial topic. The diagnosis is difficult, given the lack of robust clinical validation of the utility of cutaneous and in vitro testing. Metal hypersensitivity after TKA is quite rare and should be considered after eliminating other causes of pain and swelling, such as low-grade infection, instability, component loosening or malrotation, referred pain, and chronic regional pain syndrome. Anecdotal observations suggest that two clinical presentations of metal hypersensitivity may occur after TKA: dermatitis or a persistent painful synovitis of the knee. Patients may or may not have a history of intolerance to metal jewelry. Laboratory studies, including erythrocyte sedimentation rate, C-reactive protein level, and knee joint aspiration, are usually negative. Cutaneous and in vitro testing have been reported to be positive, but the sensitivity and specificity of such testing has not been defined. Some reports suggest that, if metal hypersensitivity is suspected and nonsurgical measures have failed, then revision to components fabricated of titanium alloy or zirconium coating can be successful in relieving symptoms. Revision should be considered as a last resort, however, and patients should be informed that no evidence-based medicine is available to guide the management of these conditions, particularly for decisions regarding revision. Given the limitations of current testing methods, the widespread screening of patients for metal allergies before TKA is not warranted.

  5. Benign hypersensitivity reactions to smallpox vaccine.

    PubMed

    Bessinger, G Todd; Smith, Sidney B; Olivere, Joseph W; James, Bruce L

    2007-05-01

    With the reinstitution of smallpox vaccinations, physicians are seeing significant numbers of adverse events for the first time since the 1980s. The most common adverse events seen in our large military population are benign. We observed a clinically and histopathologically distinct reaction pattern that has not been fully characterized previously. All smallpox-vaccinated patients at Fort Hood, Texas with adverse cutaneous reactions were referred to the dermatology clinic at Darnall Army Community Hospital. Patients were evaluated by a staff dermatologist who performed a skin biopsy and took clinical photographs. If the patients had intact vesicles or pustules, direct fluorescent antibody testing, viral and bacterial cultures, and polymerase chain reaction (PCR) assays were also performed. Three hypersensitivity reaction patterns were seen: exanthematous, erythema multiforme-like (EM-like), and urticarial. The patterns had distinct clinical and histopathologic findings. Of the 11,058 vaccinees, six had the exanthematous reaction pattern, two had the urticarial reaction pattern, and one had the EM-like pattern. We describe a new exanthematous type of hypersensitivity reaction to the smallpox vaccine. Hypersensitivity reactions occur at a rate higher than previously reported. In a carefully screened military population, these three hypersensitivity reactions are much more common than life-threatening or serious reactions. Although the reactions have distinct clinical and pathologic features, they are all characterized by mild or absent systemic symptoms and a benign outcome.

  6. Anticonvulsant hypersensitivity syndrome secondary to carbamazepine

    PubMed Central

    Brown, Shannon C.

    2017-01-01

    Anticonvulsant hypersensitivity syndrome (AHS) is a potentially fatal multiorgan drug reaction that presents with various cutaneous eruptions. There is a genetic predisposition to such reactions. We present a young woman with AHS due to carbamazepine that presented as an atypical erythema multiforme with elevated liver enzymes. PMID:28127149

  7. Metal Hypersensitivity and Total Knee Arthroplasty

    PubMed Central

    Lachiewicz, Paul F.; Watters, Tyler Steven; Jacobs, Joshua J.

    2015-01-01

    Metal hypersensitivity in patients with a total knee arthroplasty (TKA) is a controversial topic. The diagnosis is difficult, given the lack of robust clinical validation of the utility of cutaneous and in vitro testing. Metal hypersensitivity after TKA is quite rare and should be considered after eliminating other causes of pain and swelling, such as low-grade infection, instability, component loosening or malrotation, referred pain, and chronic regional pain syndrome. Anecdotal observations suggest that two clinical presentations of metal hypersensitivity may occur after TKA: dermatitis or a persistent painful synovitis of the knee. Patients may or may not have a history of intolerance to metal jewelry. Laboratory studies, including erythrocyte sedimentation rate, C-reactive protein level, and knee joint aspiration, are usually negative. Cutaneous and in vitro testing have been reported to be positive, but the sensitivity and specificity of such testing has not been defined. Anecdotal reports suggest that, if metal hypersensitivity is suspected and nonsurgical measures have failed, then revision to components fabricated of titanium alloy or zirconium coating can be successful in relieving symptoms. Revision should be considered as a last resort, however, and patients should be informed that no evidence-based medicine is available to guide the management of these conditions, particularly for decisions regarding revision. Given the limitations of current testing methods, the widespread screening of patients for metal allergies before TKA is not warranted. PMID:26752739

  8. Anticonvulsant hypersensitivity syndrome: incidence, prevention and management.

    PubMed

    Knowles, S R; Shapiro, L E; Shear, N H

    1999-12-01

    Although the anticonvulsant hypersensitivity syndrome was first described in 1950, confusion still abounds regarding the syndrome. The triad of fever, rash and internal organ involvement occurring 1 to 8 weeks after exposure to an anticonvulsant heralds this rare (1 in 1,000 to 10,000 exposures) but serious reaction. Aromatic anticonvulsants [phenytoin, phenobarbital (phenobarbitone) and carbamazepine] are the most frequently involved drugs; however, there have also been several cases of anticonvulsant hypersensitivity syndrome associated with lamotrigine. Fever, in conjunction with malaise and pharyngitis, is often the first sign. This is followed by a rash which can range from a simple exanthem to toxic epidermal necrolysis. Internal organ involvement usually involves the liver, although other organs such as the kidney, CNS or lungs may be involved. Hypothyroidism may be a complication in these patients approximately 2 months after occurrence of symptoms. The aromatic anticonvulsants are metabolised to hydroxylated aromatic compounds, such as arene oxides. If detoxification of this toxic metabolite is insufficient, the toxic metabolite may bind to cellular macromolecules causing cell necrosis or a secondary immunological response. Cross-reactivity among the aromatic anticonvulsants may be as high as 75%. In addition, there is a familial tendency to hypersensitivity to anticonvulsants. Discontinuation of the anticonvulsant is essential in patients who develop symptoms compatible with anticonvulsant hypersensitivity syndrome. A minimum battery of laboratory tests, such as liver transaminases, complete blood count and urinalysis and serum creatinine, should be performed. Corticosteroids are usually administered if symptoms are severe. Patients with anticonvulsant hypersensitivity syndrome should avoid all aromatic anticonvulsants; benzodiazepines, valproic acid (sodium valproate) or one of the newer anticonvulsants can be used for seizure control. However, valproic

  9. 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

  10. Low-dose methotrexate-induced acute interstitial pneumonitis: Report of two cases from South India and review of literature

    PubMed Central

    Iyyadurai, Ramya; Carey, Ronald Albert Benton; Satyendra, Sowmya

    2016-01-01

    Methotrexate (MTX) is an antimetabolite used as a disease-modifying agent for various rheumatological conditions. We report two patients who were treated with daily low-dose MTX and developed acute interstitial pneumonitis requiring hospital admission. MTX-induced pneumonitis is a rare life-threatening side effect, high index of clinical suspicion is required, treatment is mainly withdrawal of MTX, supportive therapy, and adjunctive steroids, outcome is good if condition is recognized early, and appropriate treatment is given. PMID:28349012

  11. 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

  12. 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.

  13. 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. Copyright © 2013 Elsevier GmbH. All rights reserved.

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

    PubMed

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

    2016-06-14

    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. 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. 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. 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.

  15. Cold hypersensitivity 6 to 10 years after replantation or revascularisation of fingers: consequences for work and leisure activities.

    PubMed

    Vaksvik, T; Hetland, K; Røkkum, M; Holm, I

    2009-02-01

    We investigated cold hypersensitivity and activity in 81 adults (male/female 76/5), 6 to 10 years after finger replantation/revascularisation (mean age at injury 43 (SD 15) years). Questionnaires included the McCabe Cold Sensitivity Severity Scale, Potential Work-Exposure Scale and the Disabilities of the Arm, Shoulder and Hand (DASH) score. Eighty per cent of the respondents were cold hypersensitive; 20% were severely or extremely cold hypersensitive. Of the 74 patients employed at injury, 7% had changed work and 4% were not working due to cold hypersensitivity. The median score for cold exposure at work at follow-up was 153 (scale 0-300). The correlation between cold sensitivity and DASH work was low. One-third of the respondents experienced limitations in their leisure activities because of cold complaints. Long-term cold sensitivity was mild or moderate for most patients. Many cold hypersensitive patients managed to continue to work even under cold conditions and cold hypersensitivity was a greater problem in leisure activities.

  16. Perceived Food Hypersensitivity Relates to Poor Asthma Control and Quality of Life in Young Non-Atopic Asthmatics

    PubMed Central

    Johnson, Jennifer; Borres, Magnus P.; Nordvall, Lennart; Lidholm, Jonas; Janson, Christer; Alving, Kjell; Malinovschi, Andrei

    2015-01-01

    Background The relationship between perceived food hypersensitivity in asthmatics, food allergen sensitization, asthma control and asthma-related quality of life has not been studied. Objective Our aim was to study the prevalence of perceived food hypersensitivity in a cohort of young asthmatics, its relation to food allergen sensitization, and any correlation to asthma control and asthma-related quality of life. Methods Perceived food hypersensitivity, as well as IgE sensitization to common food allergens, levels of exhaled nitric oxide (FeNO), and blood eosinophil counts (B-Eos) were assessed in 408 subjects (211 women) with asthma, aged (mean ± SEM) 20.4 ± 0.3 years. Subjects filled out the Asthma Control Test (ACT) and the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ). Inflammation was assessed by means of FeNO and B-Eos. Results Fifty-three per cent of subjects reported food hypersensitivity. A corresponding food allergen sensitization was found in 68% of these subjects. Non-atopic subjects with perceived food hypersensitivity (n = 31) had lower ACT (19 (15 - 22) vs. 21 (20 - 23), p < 0.001) and Mini-AQLQ -scores (5.3 (4.3 - 6.1) vs. 6.1 (5.5 - 6.5), p < 0.001) than subjects with no food hypersensitivity (n = 190), despite lower levels of FeNO and B-Eos (p < 0.05). Conclusions and Clinical Relevance Food hypersensitivity was commonly reported among young asthmatics. In a majority of cases, a corresponding food allergen sensitization was found. A novel and clinically important finding was that non-atopic subjects with perceived food hypersensitivity were characterized by poorer asthma control and asthma-related quality of life. PMID:25923451

  17. 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.

  18. Pneumonitis with Diffuse Alveolar Hemorrhage Induced by Sho-seiryu-to.

    PubMed

    Tsuchiya, Kazuo; Toyoshima, Mikio; Suda, Takafumi

    2017-10-01

    A 78-year-old man presented with acute-onset fever and dyspnea. He had been taking Sho-seiryu-to for allergic rhinitis. A chest radiograph showed diffuse bilateral ground-glass opacities with subpleural sparing, crazy-paving pattern, and traction bronchiectasis. The patient's bronchoalveolar lavage fluid was bloody and transbronchial lung biopsy specimens showed alveolitis, organizing pneumonia, and type 2 alveolar epithelial cell proliferation. There were no clinical and laboratory findings suggestive of respiratory tract infection or connective tissue disease. Based on the clinical course and the exclusion of other etiologies, Sho-seiryu-to-induced pneumonitis with diffuse alveolar hemorrhage was considered. The patient's pneumonitis resolved after the discontinuation of the drug and the administration of systemic corticosteroid therapy.

  19. Interstitial pneumonitis in a patient with chronic hepatitis C and chronic renal failure on interferon therapy.

    PubMed

    Kang, Eun Jung; Kim, Dong Kyun; Jeon, Seong Ran; Choi, Hyun Sook; Jeong, Soung Won; Jang, Jae Young; Lee, Joon Seong; Uh, Soo Taek

    2011-07-01

    After 4-months of alpha interferon (IFN-α), a 64-year old woman with chronic hepatitis C developed a cough and dyspnea and showed diffuse infiltrative opacities on her chest X-ray. Her symptoms persisted after stopping the IFN-α therapy. Pulmonary function testing revealed a reduced forced vital capacity. High-resolution computed tomography of the lung showed peripheral and peribronchovascular ground glass attenuation and consolidation associated with reticulation. Bronchoalveolar lavage was performed for further evaluation and showed a lymphocyte level of 8.2%, an uncommon finding in IFN-α-induced interstitial pneumonitis. We performed a lung biopsy to diagnose her disease and it suggested interstitial pneumonitis. This was considered to be due to the immunomodulatory effects of INF-α. Although rare, any sign of significant pulmonary involvement should be evaluated.

  20. [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.

  1. Clinical and Pathological Evaluation of Sulbactam/Ampicillin for Treatment of Experimental Bovine Pneumonic Pasteurellosis

    PubMed Central

    Gifford, Glen A.; Potter, Andrew A.; Babiuk, Lorne A.

    1988-01-01

    An experiment was conducted to evaluate the efficacy of sulbactam/ampicillin for treatment of bovine pneumonic pasteurellosis. Twenty-one Hereford calves were experimentally infected with bovine herpesvirus-1 and an ampicillin-resistant strain of Pasteurella haemolytica, then treated for three days with either sulbactam/ampicillin, chloramphenicol, or a placebo. The treatments were evaluated by comparing clinical illness scores, total sick days, weight changes, mortality rates, and postmortem lung scores between treatment groups. Both antibiotics were highly effective in reducing respiratory disease in the experimentally infected calves. The clinical response to sulbactam/ampicillin treatment was comparable with that of chloramphenicol and was significantly improved compared with the response to the placebo treatment. These findings suggest that the efficacy of sulbactam/ampicillin may be comparable to that of chloramphenicol for treatment of pneumonic pasteurellosis involving ampicillin-resistant strains of P. haemolytica. PMID:17422967

  2. 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.

  3. 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

  4. An Encapsulated Yersinia pseudotuberculosis Is a Highly Efficient Vaccine against Pneumonic Plague

    PubMed Central

    Derbise, Anne; Cerdà Marín, Alba; Ave, Patrick; Blisnick, Thierry; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E.

    2012-01-01

    Background Plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis, the recent ancestor of Yersinia pestis, provided protection against bubonic plague. However, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined. Methodology and Principal Findings The sequenced Y. pseudotuberculosis IP32953 has been irreversibly attenuated by deletion of genes encoding three essential virulence factors. An encapsulated Y. pseudotuberculosis was generated by cloning the Y. pestis F1-encoding caf operon and expressing it in the attenuated strain. The new V674pF1 strain produced the F1 capsule in vitro and in vivo. Oral inoculation of V674pF1 allowed the colonization of the gut without lesions to Peyer's patches and the spleen. Vaccination induced both humoral and cellular components of immunity, at the systemic (IgG and Th1 cells) and the mucosal levels (IgA and Th17 cells). A single oral dose conferred 100% protection against a lethal pneumonic plague challenge (33×LD50 of the fully virulent Y. pestis CO92 strain) and 94% against a high challenge dose (3,300×LD50). Both F1 and other Yersinia antigens were recognized and V674pF1 efficiently protected against a F1-negative Y. pestis. Conclusions and Significance The encapsulated Y. pseudotuberculosis V674pF1 is an efficient live oral vaccine against pneumonic plague, and could be developed for mass vaccination in tropical endemic areas to control pneumonic plague transmission and mortality. PMID:22348169

  5. An encapsulated Yersinia pseudotuberculosis is a highly efficient vaccine against pneumonic plague.

    PubMed

    Derbise, Anne; Cerdà Marín, Alba; Ave, Patrick; Blisnick, Thierry; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E

    2012-01-01

    Plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis, the recent ancestor of Yersinia pestis, provided protection against bubonic plague. However, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined. The sequenced Y. pseudotuberculosis IP32953 has been irreversibly attenuated by deletion of genes encoding three essential virulence factors. An encapsulated Y. pseudotuberculosis was generated by cloning the Y. pestis F1-encoding caf operon and expressing it in the attenuated strain. The new V674pF1 strain produced the F1 capsule in vitro and in vivo. Oral inoculation of V674pF1 allowed the colonization of the gut without lesions to Peyer's patches and the spleen. Vaccination induced both humoral and cellular components of immunity, at the systemic (IgG and Th1 cells) and the mucosal levels (IgA and Th17 cells). A single oral dose conferred 100% protection against a lethal pneumonic plague challenge (33×LD(50) of the fully virulent Y. pestis CO92 strain) and 94% against a high challenge dose (3,300×LD(50)). Both F1 and other Yersinia antigens were recognized and V674pF1 efficiently protected against a F1-negative Y. pestis. The encapsulated Y. pseudotuberculosis V674pF1 is an efficient live oral vaccine against pneumonic plague, and could be developed for mass vaccination in tropical endemic areas to control pneumonic plague transmission and mortality.

  6. A selenocysteine derivative therapy affects radiation-induced pneumonitis in the mouse.

    PubMed

    Kunwar, Amit; Jain, V K; Priyadarsini, K I; Haston, Christina K

    2013-10-01

    The mechanism leading to the radiation-induced lung response of pneumonitis is largely unknown. Here we investigated whether treatment with 3,3'-diselenodipropionic acid (DSePA), which reduces radiation-induced oxidative stress in acute response models, decreases the lung response to irradiation. Mice of the C3H/HeJ (alveolitis/pneumonitis-responding) strain received 18 Gy whole-thorax irradiation, and a subset of these mice was treated with DSePA (2 mg/kg) three times per week, beginning at 2 hours after radiation treatment, and continuing in the postirradiation period until death because of respiratory distress symptoms. DSePA treatment increased the postirradiation survival time of mice by an average of 32 days (P = 0.0002). Radiation-treated and DSePA-treated mice presented lower levels of lipid peroxidation and augmented glutathione peroxidase in the lungs, compared with those levels measured in mice receiving radiation only, when mice receiving radiation only were killed because of distress symptoms, whereas catalase and superoxide dismutase levels did not show consistent differences among treatment groups. DSePA treatment decreased pneumonitis and the numbers of mast cells, neutrophils, and lymphocytes in the lungs and bronchoalveolar lavage, respectively, of irradiated mice relative to mice exposed to radiation alone. DSePA treatment also decreased the radiation-induced increase in granulocyte colony-stimulating factor levels in the bronchoalveolar lavage and lung-tissue expression of intercellular adhesion molecule-1 and E-selectin, while increasing the expression of glutathione peroxidase-4. We conclude that DSePA treatment reduces radiation-induced pneumonitis in mice by delaying oxidative damage and the inflammatory cell influx.

  7. 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. © 2015 Japanese Dermatological Association.

  8. [Prevalence of latex hypersensitivity among medical personnel].

    PubMed

    Camacho Ibarra, V C; López García, A I; Galindo García, J A; Paz Martínez, D; Papaqui Tapia, J S

    1997-01-01

    In order to determine the latex hypersensitivity prevalence in medical residents from Hospital Universitario de Puebla, it was carried out a transversal, observational and descriptive study including the medical staff of all specialties. The epicutancous test was effectuated with 1:20 latex antigen dilution. It was studied a total of 90 medical residents, 68.9% were males and 31.1% females. The mean age was 30.6 years (SD 3.8). The 50% were from clinical specialties and 50% else were from surgical. The global latex hypersensitivity prevalence was 8%. It will be convenient to carry out a follow up of studied cohort to establish if continual exposition, years later, will determine skin reactivity to latex in professional practice.

  9. 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.

  10. Pharmacogenetics of antiepileptic drug-induced hypersensitivity.

    PubMed

    Bloch, Katarzyna M; Sills, Graeme J; Pirmohamed, Munir; Alfirevic, Ana

    2014-04-01

    Antiepileptic drugs can induce potentially life-threatening hypersensitivity reactions such as Stevens-Johnson syndrome at a frequency of one in 10,000 to one in 1000 treated patients. There is a considerable cross-reactivity among different antiepileptic drugs but the mechanisms are not known. In this review we have summarized current evidence on antiepileptic drug-induced hypersensitivity reactions and performed meta-analyses of published case-control studies that investigated associations between HLA alleles and several antiepileptic drugs in diverse populations. As the heterogeneity between studies was high, we conducted subsequent subgroup analyses and showed that HLA-B*15:02 was associated with carbamazepine, lamotrigine and phenytoin-induced Stevens-Johnson syndrome in Asian populations indicating that pretreatment testing may prevent cross-reactivity. Additionally, we explored the potential of new, high-throughput technologies that may help to understand the mechanisms and predict the risk of adverse drug reactions in the future.

  11. [Rare, severe hypersensitivity reaction to potassium iodide].

    PubMed

    Korsholm, Anne Sofie; Ebbehøj, Eva; Richelsen, Bjørn

    2014-07-07

    The literature reports a large variety of adverse reactions to potassium iodide. A severe hypersensitivity reaction to potassium iodide in a 51-year-old woman with Graves' thyrotoxicosis is described. Following administration the patient developed sialadenitis, conjunctivitis, stomatitis and acneiform iododerma that responded dramatically to withdrawal of the potassium iodide and administration with corticosteroids. Awareness of these adverse reactions may prevent prolonged hospitalization and unnecessary tests and treatments.

  12. 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.

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

    PubMed Central

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

    2010-01-01

    Iron acquisition from the host is an important step in the pathogenic process. While Yersinia pestis has multiple iron transporters, the yersiniabactin (Ybt) siderophore-dependent system plays a major role in iron acquisition in vitro and in vivo. In this study, we determined that the Ybt system is required for the use of iron bound by transferrin and lactoferrin and examined the importance of the Ybt system for virulence in mouse models of bubonic and pneumonic plague. Y. pestis mutants unable to either transport Ybt or synthesize the siderophore were both essentially avirulent via subcutaneous injection (bubonic plague model). Surprisingly, via intranasal instillation (pneumonic plague model), we saw a difference in the virulence of Ybt biosynthetic and transport mutants. Ybt biosynthetic mutants displayed an ∼24-fold-higher 50% lethal dose (LD50) than transport mutants. In contrast, under iron-restricted conditions in vitro, a Ybt transport mutant had a more severe growth defect than the Ybt biosynthetic mutant. Finally, a Δpgm mutant had a greater loss of virulence than the Ybt biosynthetic mutant, indicating that the 102-kb pgm locus encodes a virulence factor, in addition to Ybt, that plays a role in the pathogenesis of pneumonic plague. PMID:20160020

  14. Immunological Aspect of Radiation-Induced Pneumonitis, Current Treatment Strategies, and Future Prospects

    PubMed Central

    Kainthola, Anup; Haritwal, Teena; Tiwari, Mrinialini; Gupta, Noopur; Parvez, Suhel; Tiwari, Manisha; Prakash, Hrideysh; Agrawala, Paban K.

    2017-01-01

    Delivery of high doses of radiation to thoracic region, particularly with non-small cell lung cancer patients, becomes difficult due to subsequent complications arising in the lungs of the patient. Radiation-induced pneumonitis is an early event evident in most radiation exposed patients observed within 2–4 months of treatment and leading to fibrosis later. Several cytokines and inflammatory molecules interplay in the vicinity of the tissue developing radiation injury leading to pneumonitis and fibrosis. While certain cytokines may be exploited as biomarkers, they also appear to be a potent target of intervention at transcriptional level. Initiation and progression of pneumonitis and fibrosis thus are dynamic processes arising after few months to year after irradiation of the lung tissue. Currently, available treatment strategies are challenged by the major dose limiting complications that curtails success of the treatment as well as well being of the patient’s future life. Several approaches have been in practice while many other are still being explored to overcome such complications. The current review gives a brief account of the immunological aspects, existing management practices, and suggests possible futuristic approaches. PMID:28512460

  15. THE RECOVERY FROM PATIENTS WITH ACUTE PNEUMONITIS OF A VIRUS CAUSING PNEUMONIA IN THE MONGOOSE

    PubMed Central

    Weir, John M.; Horsfall, Frank L.

    1940-01-01

    1. A virus capable of producing pulmonary consolidation in the wild mongoose (Herpestes griseus) has been isolated from throat washings obtained from four patients with a clinical syndrome termed acute pneumonitis. 2. The virus was not pathogenic for ferrets, mice, guinea pigs, rabbits, monkeys, voles, hamsters, deer mice, skunks, opossums, or woodchucks. 3. The virus was filterable through Berkefeld V and N candles, was not inactivated by glycerin or by freezing and drying in vacuum, and was propagated for at least 30 serial passages on the chorio-allantoic membrane of the developing chick embryo. 4. Normal mongooses placed in contact with infected mongooses developed pulmonary consolidation. 5. The virus was neutralized by the serum of mongooses convalescent from the infection but was not neutralized by normal mongoose serum. 6. Serum of human beings convalescent from acute pneumonitis also neutralized the virus, but serum obtained from the same individuals during the acute phase of the disease failed to do so. 7. The evidence so far obtained strongly suggests that this virus is the cause of acute pneumonitis in human beings. It differs from other viruses known to cause infections of the respiratory tract in man. PMID:19871045

  16. 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

  17. TRPA1 contributes to cold hypersensitivity.

    PubMed

    del Camino, Donato; 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

    2010-11-10

    TRPA1 is a nonselective cation channel expressed by nociceptors. Although 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 in which reactive oxygen species and proinflammatory 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 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide] reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain.

  18. Drug hypersensitivity: pharmacogenetics and clinical syndromes.

    PubMed

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

    2011-03-01

    Severe cutaneous adverse reactions include syndromes such as drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). An important advance has been the discovery of associations between HLA alleles and many of these syndromes, including abacavir-associated hypersensitivity reaction, allopurinol-associated 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 severe cutaneous adverse reactions. The rollout 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, in which the positive predictive value of HLA-B∗1502 is low and the negative predictive value of HLA-B∗1502 for SJS/TEN might not be 100% in all ethnic groups. International collaborative consortia have been formed with the goal of developing phenotypic standardization and undertaking HLA and genome-wide analyses in diverse populations with these syndromes.

  19. 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.

  20. 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

  1. Hypersensitivity reactions to fluoroquinolones: analysis of the factors involved.

    PubMed

    Blanca-López, N; Ariza, A; Doña, I; Mayorga, C; Montañez, M I; Garcia-Campos, J; Gomez, F; Rondón, C; Blanca, M; Torres, M J

    2013-05-01

    Hypersensitivity reactions to fluoroquinolones seem to be on the increase, especially immediate type reactions. The aim of this study was to determine whether several conditions, including gender, age, type of reaction, time interval between the reaction and the study, type of symptoms, the specific fluoroquinolone involved in the reaction and previous confirmed hypersensitivity to betalactams or to other drugs were factors contributing to the development of hypersensitivity to fluoroquinolones. We analysed retrospectively all patients attending our allergy department between January 2005 and December 2010 because of a reaction associated with fluoroquinolone administration. The diagnosis was confirmed by basophil activation test or drug provocation tests. In accordance with the results, patients were then classified as having hypersensitivity or non-hypersensitivity to fluoroquinolones. A group of 218 patients was evaluated; 69 were confirmed as having hypersensitivity, 146 as non-hypersensitivity and 3 were excluded. Comparisons between groups showed that the allergic patients more often had a previous confirmed hypersensitivity to betalactams (P = 0.029), immediate reactions (P = 0.001) and anaphylaxis (P = 0.000), and moxifloxacin was the fluoroquinolone most frequently involved (P = 0.027). The logistic regression analysis showed three factors associated with the diagnosis of hypersensitivity reactions to fluoroquinolones: previous hypersensitivity to betalactams (OR: 4.571; 95% CI: 0.987-21.171; adjusted OR: 23.654; 95% CI: 1.529-365.853), immediate reactions (OR: 17.333; 95% CI: 4.374-68.691; adjusted OR: 52.493; 95% CI: 6.621-416.200) and reactions induced by moxifloxacin (OR: 3.091; 95% CI: 1.160-8.239; adjusted OR: 13.610; 95% CI: 2.419-76.565). In patients who develop reactions to fluoroquinolones, hypersensitivity is more often confirmed in those with immediate reactions and when moxifloxacin is involved. Moreover, patients with hypersensitivity to

  2. Delayed Cutaneous Hypersensitivity Reactions in Patients With Kaposi's Sarcoma

    PubMed Central

    Taylor, J. F.; Ziegler, J. L.

    1974-01-01

    Defects in cellular immunocompetence have been sought in 25 patients with Kaposi's sarcoma. Skin tests with recall antigens, and PHA lymphocyte stimulation in vitro showed that efferent delayed hypersensitivity responses are intact in the majority. However, attempted sensitization and subsequent challenge with DNCB demonstrated that the afferent limb of the responses was impaired in some patients. This did not appear to be related to the morphology of the tumour or to prognosis. Tumour specific reactions were demonstrated both in vivo and in vitro and these correlated significantly with the morphology and histology. The interpretation of the results for an individual is confounded by the multiplicity of factors influencing the outcome in a particular patient. PMID:4447775

  3. PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis

    PubMed Central

    Wu, Jiaying; Hong, Dongsheng; Zhang, Xiangnan; Lu, Xiaoyang; Miao, Jing

    2017-01-01

    Therapies that targeted PD-1 have shown remarkable rates of durable clinical responses in patients with various tumor types. However, the extent and knowledge of pulmonary toxicities associated with PD-1 blockade, mainly manifested as pneumonitis, remains obscure. In this study, a total of 6360 subjects from 16 phase II/III clinical trials were pooled for meta-analysis to evaluate the overall incidence and risk of PD-1 inhibitors-related pneumonitis in cancer patients. The incidence of pneumonitis during anti-PD-1 immunotherapy was 2.92% (95%CI: 2.18–3.90%) for all-grade and 1.53% (95%CI: 1.15–2.04%) for high-grade pneumonitis. Compared with routine chemotherapy, PD-1 inhibitors were associated with a significant increased risk of pneumonitis. Moreover, among the types of tumor treated with PD-1 inhibitors, the melanoma patients have the lowest incidence of pneumonitis, while the non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) patients have the highest. Furthermore, no significant differences were detected in the incidences of all- and high-grade pneumonitis between high-dose and low-dose groups of PD-1 inhibitors. In conclusion, PD-1 inhibitors were probably associated with an increased risk of pneumonitis in a dose-independent manner, compared with routine chemotherapeutic agents. The frequency and severity of treatment-mediated pneumonitis was quite different in patients with various tumor types. PMID:28272463

  4. Diagnosis of Polistes wasp hypersensitivity.

    PubMed

    Grant, J A; Rahr, R; Thueson, D O; Lett-Brown, M A; Hokanson, J A; Yunginger, J W

    1983-10-01

    Patients referred from the Houston, Texas, metropolitan area were evaluated for allergic reactions to insect stings. Forty-eight persons reported at least one systemic reaction caused by a Polistes paper-nest wasp sting. Honey bees, imported fire ants, and other types of Hymenoptera were identified in that order by 19 other subjects with systemic allergic reactions. Life-threatening airway obstruction and/or hypotension were noted by most of our patients. Wasp venom skin testing was positive in 65% of subjects reporting sensitivity to this insect. Skin testing was correlated quantitatively with basophil histamine release, and qualitatively with RAST assays using Polistes wasp venom. Venoms from common species of Polistes were highly cross-reactive as shown by RAST and basophil histamine release. Patients having a positive history and laboratory response (by skin testing, histamine release, or RAST) to Polistes wasp venom also were positive to bee venom about 20% of the time and to another vespid (hornet or yellow jacket) over 50% of the time.

  5. 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

  6. 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

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

    PubMed

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

    2015-01-01

    No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis. VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral

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

    SciTech Connect

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

    2006-07-01

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

  10. A Novel Method to Incorporate the Spatial Location of the Lung Dose Distribution into Predictive Radiation Pneumonitis Modeling

    SciTech Connect

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

    2012-03-15

    Purpose: Studies have proposed that patients who receive radiation therapy to the base of the lung are more susceptible to radiation pneumonitis than patients who receive therapy to the apex of the lung. The primary purpose of the present study was to develop a novel method to incorporate the lung dose spatial information into a predictive radiation pneumonitis model. A secondary goal was to apply the method to a 547 lung cancer patient database to determine whether including the spatial information could improve the fit of our model. Methods and Materials: The three-dimensional dose distribution of each patient was mapped onto one common coordinate system. The boundaries of the coordinate system were defined by the extreme points of each individual patient lung. Once all dose distributions were mapped onto the common coordinate system, the spatial information was incorporated into a Lyman-Kutcher-Burman predictive radiation pneumonitis model. Specifically, the lung dose voxels were weighted using a user-defined spatial weighting matrix. We investigated spatial weighting matrices that linearly scaled each dose voxel according to the following orientations: superior-inferior, anterior-posterior, medial-lateral, left-right, and radial. The model parameters were fit to our patient cohort with the endpoint of severe radiation pneumonitis. The spatial dose model was compared against a conventional dose-volume model to determine whether adding a spatial component improved the fit of the model. Results: Of the 547 patients analyzed, 111 (20.3%) experienced severe radiation pneumonitis. Adding in a spatial parameter did not significantly increase the accuracy of the model for any of the weighting schemes. Conclusions: A novel method was developed to investigate the relationship between the location of the deposited lung dose and pneumonitis rate. The method was applied to a patient database, and we found that for our patient cohort, the spatial location does not influence

  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. 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

  13. 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.

  14. Multiple organ dysfunction syndrome: infection or hypersensitivity reaction?

    PubMed

    Dreesman, Alexandra; Hoorens, Anne; Hachimi-Idrissi, Said

    2010-08-01

    Anticonvulsant hypersensitivity syndrome is a potentially life-threatening delayed hypersensitivity reaction characterized by the triad of fever, rash and multiorgan involvement, which usually occurs within the first weeks of introduction of an antiepileptic drug. It mimics several life-threatening diseases, which makes it potentially difficult to recognize. We describe the case of a 6-year-old boy admitted with anticonvulsant hypersensitivity syndrome after the association of lamotrigine treatment with sodium valproic acid for reluctant epilepsy.

  15. Two factors responsible for the development of denervation hypersensitivity

    PubMed Central

    Jones, Rosemary; Vrbová, Gerta

    1974-01-01

    1. Innervated adult skeletal muscle is sensitive to acetylcholine at the end-plate region only. After denervation the entire muscle membrane becomes chemosensitive. The period of greatest increase in sensitivity in rat soleus muscles following section of the sciatic nerve in the thigh is between 48 and 72 hr post-operatively. 2. Direct electrical stimulation was found to prevent the onset of the development of denervation hypersensitivity during the first 2-3 days after nerve section. Thereafter, electrical stimulation only reduced the sensitivity of denervated muscles to acetylcholine (ACh). 3. The period of greatest increase in sensitivity follows loss of transmission and degeneration of the nerve terminals. Once this degeneration is under way, electrical stimulation is no longer as effective in preventing the development of denervation hypersensitivity. 4. Hypersensitivity is also seen in muscles on which a small piece of thread or degenerating nerve has been placed. Hypersensitivity following these procedures declines within a few days, unlike denervation hypersensitivity which persists until innervation is restored. 5. The present results suggest that activity alone cannot prevent the development of hypersensitivity in the presence of degenerating nerve fibres, or muscle damage. Activity does however counteract increased sensitivity. It is suggested that two factors interact to produce denervation hypersensitivity; the presence of degenerating nerve tissue and concomitant cellular changes bring about changes in the muscle fibre membrane causing it to become hypersensitive; and the loss of muscle activity, resulting in the persistence of hypersensitivity until innervation is restored. ImagesPlate 1 PMID:4822574

  16. 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.

  17. X-ray induction of persistent hypersensitivity to mutation

    SciTech Connect

    Frank, J.P.; Williams, J.R.

    1982-04-16

    The progeny of x-irradiated V79 cells are hypersensitive to PUVA-(8-methoxypsoralen plus longwave ultraviolet light) induced mutation at the locus for hypoxanthine-guanine phosphoribosyl transferase. This hypersensitivity is most evident at low doses of pUVA that do not induce mutation in non-x-irradiated cells. The hypersensitivity is evoked by x-irradiation delivered as a single dose or as multiple fractions over a long period and persists for at least 108 days of exponential growth. This radiation-induced hypersensitivity to subsequent mutation is a new phenomenon that may be relevant to multistage carcinogenesis.

  18. 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.

  19. [HLA-B*5701 and abacavir hypersensitivity reaction].

    PubMed

    Servonnet, A; Leclercq, E; Delacour, H; Ceppa, F

    2010-12-01

    A potentially life-threatening hypersensitive reaction occurs in association with initiation of HIV nucleoside analogue abacavir therapy in 4 to 8% of patients. Preliminary studies appear to confirm the role of the immune system in abacavir hypersensitivity. The reaction is possibly the result of presentation of drug peptides onto HLA, that may induce a pathogenic T-cell response. Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele and prospective HLA-B*5701 genetic screening has now been instituted in clinical practice to reduce the risk of hypersensitivity reaction. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  20. The importance of interleukin-8 as a neutrophil chemoattractant in the lungs of cattle with pneumonic pasteurellosis.

    PubMed Central

    Caswell, J L; Middleton, D M; Gordon, J R

    2001-01-01

    Interleukin-8 (IL-8), an in vitro and in vivo neutrophil chemoattractant, is expressed at high levels in the lesions observed in bovine pneumonic pasteurellosis. Because of the role of neutrophils in the pathogenesis of pneumonic pasteurellosis, we investigated the relative importance of IL-8 as a neutrophil chemoattractant in this disease. Bronchoalveolar lavage (BAL) fluid was harvested from calves experimentally infected with bovine herpesvirus-1 and challenged with Mannheimia haemolytica. Neutrophil chemotactic activity was measured in pneumonic BAL fluid samples treated with a neutralizing monoclonal antibody to ovine IL-8, and compared to the activity in samples treated with an isotype-matched control antibody. Bronchoalveolar lavage fluid was analyzed at a dilution which induced a half-maximal response, and the concentrations of antibody were optimized in a preliminary experiment. Following incubation of replicate samples of diluted pneumonic bovine BAL fluid with 70 microg/mL of IL-8-neutralizing antibody or control antibody, the neutrophil chemotactic activities of the samples were determined using an in vitro microchemotaxis assay. Overall, pretreatment of BAL fluid samples with neutralizing anti-IL-8 antibody reduced neutrophil chemotactic activity by 15% to 60%, compared to pretreatment with control antibody. This effect was highly significant (P < 0.001), and was present in 5 of 5 samples. These data indicate that IL-8 is an important neutrophil chemoattractant in calves with pneumonic pasteurellosis, but that mediators with actions redundant to those of IL-8 must also be present in the lesions. PMID:11768129

  1. 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.

  2. Use of contact hypersensitivity in immunotoxicity testing.

    PubMed

    Descotes, Jacques

    2010-01-01

    The histopathological examination of lymphoid organs together with a T-dependent antibody (TDAR) assay are the primary components of preclinical immunotoxicity assessment. Additional testing including measurement of cellular immunity may be considered. Besides ex vivo lymphocyte proliferation assays, either delayed or contact hypersensitivity models can be used. Contact hypersensitivity testing is typically performed either in mice or in guinea pigs and is directly derived from classical models used for the detection of contact sensitizing chemicals. Whatever the selected model, it is comprised of a sensitizing phase where the animals are applied a strong contact sensitizer topically, then a rest phase, and finally an eliciting phase where sensitized animals are challenged topically with the same contact sensitizer.In mice, the ear-swelling test is the reference procedure in which mice are sensitized to the ear or shaved abdominal skin and then challenged on the ear. Ear swelling usually measured from ear thickness reflects a cell-mediated immune response. In guinea pigs, a strong sensitizer is applied on the shaved skin of the abdomen or the interscapular area. The sensitized animals are challenged on another area of the shaved abdomen, and the cell-mediated response is assessed semiquantitatively from the magnitude of induced erythema inconsistently associated with edema. Treatment or exposure with immunosuppressive chemicals can result in a significantly decreased ear swelling or skin reaction. Contact hypersensitivity models are seldom used nowadays in preclinical immunotoxicity testing, most likely because of the lack of standardization and extensive validation as well as their use being restricted to mice or guinea pigs.

  3. Laryngeal sensory dysfunction in laryngeal hypersensitivity syndrome.

    PubMed

    Vertigan, Anne E; Bone, Sarah L; Gibson, Peter G

    2013-08-01

    Diseases associated with laryngeal dysfunction include chronic refractory cough (CRC), paradoxical vocal fold movement (PVFM), muscle tension dysphonia (MTD) and globus pharyngeus. We hypothesized the presence of a common sensory laryngeal dysfunction, the 'laryngeal hypersensitivity' syndrome, in these conditions. The aim of the study was to compare symptoms and sensory function in patients with CRC, PVFM, MTD and globus. The 103 participants included healthy controls (n = 13) and four case groups: CRC (n = 33), PVFM (n = 28), globus pharyngeus (n = 11) and MTD (n = 18). Participants completed self-report questionnaires: Symptom Frequency and Severity Scale, Voice Handicap Index and the Laryngeal Paraesthesia Questionnaire; and quantitative sensory testing: capsaicin cough reflex sensitivity, hypertonic saline challenge, the timed swallow test, acoustic voice testing, cough frequency monitor and a voice stress test. All case groups reported a high-symptom burden in comparison to controls. The case groups showed a similar pattern of symptoms, with impairment in each of the cough, respiration, vocal and upper airway symptom domains. Objective testing revealed significant sensory impairment in the case groups compared to controls and also showed an overlap in sensory dysfunction between the four case groups. Furthermore, there was cross-sensory stimulation of symptoms whereby stimulation of a particular response resulted in symptoms in another domain. These discrete clinical laryngeal syndromes display considerable overlap in their clinical features and a common sensory dysfunction, supporting the 'laryngeal hypersensitivity' hypothesis. Reconceptualizing functional laryngeal disorders as a form of laryngeal hypersensitivity syndrome provides an alternative approach to management of these perplexing conditions. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

  4. 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

  5. Lymphocyte transformation studies in drug hypersensitivity.

    PubMed

    Warrington, R J; Tse, K S

    1979-05-05

    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.

  6. LLLT in treating dentinary hypersensitivity: new concepts

    NASA Astrophysics Data System (ADS)

    Brugnera, Aldo, Jr.; Zanin, Fatima; Ladalardo, Thereza C.; Pinheiro, Antonio; Pecora, Jesus D.

    2006-02-01

    Dental hypersensitivity has been studied for several years and it is reported as a strikingly painful condition originating from the exposition of dentinal tubuli . The exposed area is subjected to several kinds of stimuli, resulting in a rapid sharp acute pain. LLLT has been shown to have antiinflammatory, analgesic and cellular effects in both hyperemia and inflammation of the dental pulp. Our previous histological study showed that irradiated animals presented an increased production of dentine and shutting of dentinal tubuli. On the other hand, non-irradiated subjects still showed signals of intense inflammatory reaction and even necrosis at the same experimental times. Irradiated teeth did not show cell degeneration. The LLLT was shown to be efficient in the stimulation of odontoblast cells, producing reparative dentin and closing dentin tubuli. Our clinical studies with 660nm, 790nm and 830nm diode laser, and the total dose per tooth of 4J/cm was shown effective in treating dentinal hypersensitivity as it quickly reduces pain and maintains a prolonged painless status in 91.27 % to 97% of the cases. In a recent study our team observed that significant levels of dentinal desensitization were only found in patients belonging to the 25-35 age group. In conclusion, the results demonstrated indeed that LLLT, when based on the use of correct irradiations parameters is effective in treating hypersensitivity, but the age of patients is one of the factors that may alter the success of treatment due to dentinal sclerosis, which makes the penetration of light more difficult.

  7. 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

  8. Drug hypersensitivity syndrome induced by meglumine antimoniate.

    PubMed

    Jeddi, Fakhri; Caumes, Eric; Thellier, Marc; Jauréguiberry, Stéphane; Mazier, Dominique; Buffet, Pierre A

    2009-06-01

    We report a case of drug hypersensitivity syndrome (drug reaction with eosinophilia and systemic symptoms [DRESS]) induced by parenteral meglumine antimoniate (Glucantime) in a 40-year-old man who traveled to Bolivia and was treated for mucocutaneous leishmaniasis. Two weeks after starting therapy, the patient had fever, joint pain, a cutaneous eruption, and hypereosinophilia (1,358 cells/mm(3)). These symptoms resolved after drug withdrawal but reappeared upon reintroduction of the drug. Pentavalent antimonials should be definitively withdrawn in patients with hypereosinophilia > 1,000 cells/mm(3) accompanied by systemic manifestations consistent with DRESS.

  9. Management of nonimmediate hypersensitivity reactions to drugs.

    PubMed

    Roujeau, Jean-Claude; Haddad, Cynthia; Paulmann, Maren; Mockenhaupt, Maja

    2014-08-01

    Nonimmediate hypersensitivity to drugs has a huge diversity of clinical presentations affecting exclusively or predominantly a single organ (most often the skin) or multiple organs. The latter is the rule with drug reaction with eosinophilia and systemic symptoms, and with drug-induced vasculitis. The management includes a dozen successive steps. Finally, the patient should be provided clear information on the suspected cause of the reaction, recommendations for follow-up after severe reactions associated with a risk of sequelae, and clear recommendations for future use of medications. Pharmacovigilance networks should be informed.

  10. Acute eosinophilic pneumonia: a hypersensitivity phenomenon?

    PubMed

    Badesch, D B; King, T E; Schwarz, M I

    1989-01-01

    A previously healthy young man presented with acute respiratory distress and diffuse bilateral infiltrates on chest radiograph. Eosinophilic pneumonia was diagnosed by bronchoalveolar lavage and confirmed by transbronchial lung biopsy. There was no evidence of an infectious etiology, and the patient rapidly improved with corticosteroid therapy. Most cases of eosinophilic pneumonia reported previously have followed a chronic course. The case presented here was acute in onset, suggesting a hypersensitivity reaction. High levels of bronchoalveolar lavage eosinophils indicate the diagnosis but not the etiology of eosinophilic pneumonia.

  11. Contribution of the Chemokine CCL2 to Mechanical Hypersensitivity Following Surgical Incision in Rats

    PubMed Central

    Peters, Christopher M.; Eisenach, James C.

    2010-01-01

    Background Neural-glial signaling in the spinal cord may underlie pain and sensitization after peripheral injury. Here we test the role of a glial activator, the chemokine CCL2 on mechanical hypersensitivity following plantar incision in a rat model of postoperative pain. Methods Twenty four hours after hindpaw incision rats were intrathecally administered an anti-CCL2 neutralizing antibody (3 μg and 10 μg) or control IgG (10 μg). Mechanical hypersensitivity was assessed acutely and for several days following administration of anti-CCL2 antibody using von Frey filaments. Immunohistochemical analysis was conducted on spinal cord sections to examine the effects of treatment on measures of microglial activation including levels of ionized calcium binding adaptor molecule 1 (IBA1) and phosphorylated p38 mitogen activated protein kinase. Results Neutralization of spinal CCL2 acutely reversed mechanical hypersensitivity within 30 minutes in a dose dependent manner. A single administration also produced a sustained decrease in mechanical hypersensitivity 48 and 72 hours following incision. Anti-CCL2 antibody reduced microglial activation as measured by the levels of IBA1 immunoreactivity and the number of microglia containing phosphorylated p38 mitogen activated protein kinase 48 hours following incision but not within 30 minutes of administration. Conclusions These results provide evidence that CCL2 contributes to the maintenance of mechanical hypersensitivity following plantar incision and establishes a role for neural glial signaling in postoperative pain. The long term effects of anti-CCL2 treatment correlate with reduced microglial activation. Spinal blockade of CCL2 may serve as a useful therapy for the treatment of certain aspects of postoperative pain. PMID:20395830

  12. Widespread hypersensitivity is related to altered pain inhibition processes in irritable bowel syndrome.

    PubMed

    Piché, Mathieu; Arsenault, Marianne; Poitras, Pierre; Rainville, Pierre; Bouin, Mickael

    2010-01-01

    The mechanisms of chronic pain in irritable bowel syndrome (IBS) have been widely investigated but remain unclear. The present study investigated the relation between visceral hypersensitivity, cutaneous thermal sensitivity, and central pain mechanisms. Rectal sensitivity was assessed with a barostat, and forearm and calf sensitivity with a contact thermode. Central mechanisms were assessed by counterirritation using sustained cold-pain to the hand and painful electric shocks to the ankle. Psychological symptoms were also assessed, using questionnaires. Female volunteers with diarrhea-predominant IBS (n=27) and healthy controls (n=25) participated in the study. IBS patients had lower rectal and calf pain thresholds compared to controls (p's<0.05). IBS patients also reported more pain than controls for rectal distensions, and heat pain on the calf and forearm (all p's<0.001). Cold-pain inhibited shock-pain in controls but not IBS patients (controls: -13.5+/-5.3 vs IBS: +1.9+/-10.5; p<0.01). In addition, visceral hypersensitivity was significantly correlated to cutaneous thermal hypersensitivity and pain inhibition deficits, although effects were only weak and moderate, respectively. Furthermore, covariance analyses indicated that psychological factors accounted for group differences in visceral hypersensitivity and pain inhibition deficits. In conclusion, this study confirms the relation between altered pain inhibition processes and widespread hypersensitivity in IBS. The present results also suggests that psychological symptoms and altered pain processing in IBS patients may reflect at least in part, common underlying mechanisms. Copyright 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  13. Radiation pneumonitis in breast cancer patients who received radiotherapy using the partially wide tangent technique after breast conserving surgery.

    PubMed

    Chung, Yoonsun; Yoon, Hong In; Kim, Yong Bae; Ahn, Seung Kwon; Keum, Ki Chang; Suh, Chang-Ok

    2012-09-01

    We assessed the risk of radiation pneumonitis (RP) in terms of dosimetric parameters in breast cancer patients, who received radiotherapy using the partially wide tangent technique (PWT), following breast conservation surgery (BCS). We analyzed the data from 100 breast cancer patients who underwent radiotherapy using PWT. The entire breast, supraclavicular lymph node, and internal mammary lymph node (IMN) were irradiated with 50.4 Gy in 28 fractions. RP was scored on a scale of 0 to 5, based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria. The dosimetric parameters, used in analysis for the ipsilateral lung, were the mean lung dose (MLD), V(5) (percentage of lung volume that received a dose of 5 Gy or more)-V(50), and normal tissue complication probability (NTCP). Of the 100 patients, three suffered from symptomatic RP (symptom grade ≥2), but were relieved by supportive care. The risk of RP was not correlated with the treatment regimen. RP associated mostly with asymptomatic minimal pulmonary radiologic change or mild dry cough developed more frequently in the group with MLD ≥20.5 Gy or NTCP ≥23% than in the group with MLD <20.5 Gy and NTCP <23% (48.6% vs. 25.4%, p=0.018). Dosimetric parameters of MLD and NTCP were correlated with the incidence of RP, but the clinical impact was minimal. We suggest that PWT is a safe technique for the treatment of IMN for BCS patients with low risk of symptomatic RP.

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

    PubMed

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

    2016-02-19

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

  15. 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

  16. Critical Protective Role for MCP-1 in Pneumonic Burkholderia mallei Infection

    PubMed Central

    Goodyear, Andrew; Jones, Abby; Troyer, Ryan; Bielefeldt-Ohmann, Helle; Dow, Steven

    2010-01-01

    Burkholderia mallei is a Gram-negative bacterial pathogen of domestic equidae and humans that can cause severe, rapidly life-threatening pneumonic infections. Little is known regarding the role of chemokines and early cellular immune responses in protective immunity to pulmonary infection with B. mallei. Although the role of MCP-1 in Gram-positive bacterial infections has been previously investigated, the role of MCP-1 in immunity to acute pneumonia caused by Gram-negative bacteria, such as B. mallei, has not been assessed. In a mouse model of pneumonic B. mallei infection, we found that both MCP-1−/− mice and CCR2−/− mice were extremely susceptible to pulmonary infection with B. mallei, compared with wild-type (WT) C57Bl/6 mice. Bacterial burden and organ lesions were significantly increased in CCR2−/− mice, compared with WT animals, following B. mallei challenge. Monocyte and dendritic cell recruitment into the lungs of CCR2−/− mice was significantly reduced in comparison with that in WT mice following B. mallei infection, whereas neutrophil recruitment was actually increased. Depletion of monocytes and macrophages prior to infection also greatly raised the susceptibility of WT mice to infection. Production of IL-12 and IFN-γ in the lungs after B. mallei infection was significantly impaired in both MCP-1−/− and CCR2−/− mice, whereas treatment of CCR2−/− mice with rIFN-γ restored protection against lethal challenge with B. mallei. Thus, we conclude that MCP-1 plays a key role in regulating cellular immunity and IFN-γ production following pneumonic infection with B. mallei and therefore may also figure importantly in other Gram-negative pneumonias. PMID:20042590

  17. Carboplatin hypersensitivity: evaluation and successful desensitization protocol.

    PubMed

    Bruchim, Ilan; Goldberg, Arnon; Fishman, Ami; Confino-Cohen, Ronit

    2014-01-01

    Carboplatin-induced immediate hypersensitivity reactions are relatively common among patients with gynecological malignancies. Once this occurs, the patient might be at risk for future carboplatin-induced reactions. This study evaluated the efficacy of allergic consultation, carboplatin skin testing and desensitization as a single intervention strategy in this population. Patients with a well-documented immediate reaction to carboplatin were offered allergy consultation, carboplatin skin testing and a desensitization plan in a single visit between scheduled chemotherapy sessions. Fifty-five patients with an immediate reaction were evaluated. After allergist assessment, 44 (89%) of 49 patients skin tested had a positive result. A total of 207 carboplatin desensitization cycles were administered to 49 women. Among them, 10 patients had a mild immediate hypersensitivity reaction during desensitization. Five patients subsequently tolerated carboplatin administered in the prolonged desensitization protocol. In the data presented, we propose a strategy that is both cost effective and very convenient for the patient. The diagnostic procedure, including allergist consultation and skin test, can be completed in less than 2 h. In most cases where carboplatin is indispensable, desensitization can be administered without overnight hospitalization.

  18. Specific Aspects of Drug Hypersensitivity in Children.

    PubMed

    Bergmann, Marcel; Caubet, Jean-Christoph

    2016-01-01

    Suspicion for drug hypersensitivity (DH) is a common reason for children's referral to an allergy department, with β-lactam antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) as the most frequently involved drugs. The prevalence of DH in children remains not well defined as epidemiologic studies in children are lacking, and the most of those take into account adverse drug reactions (ADR) without a systematic allergy work-up to confirm or exclude hypersensitivity. The clinical history is mandatory in order to classify the reaction as being immediate or non-immediate and then to subsequently adapt the allergy work-up. Mainly due to the lack of studies, the same guidelines used for diagnosis of drug allergy in adults are generally used in the pediatric population, and the diagnosis is based mainly on in vivo tests (i.e. skin tests and/or drug provocation test) and rarely on in vitro tests. However, specific aspects of management of DH in children have been recently highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    PubMed

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

    1998-01-01

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

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

    PubMed Central

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

    2008-01-01

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

  1. 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

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

    SciTech Connect

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

    1986-01-01

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

  3. Pleuropericarditis, obliterative bronchiolitis and lymphocytic interstitial pneumonitis after allogeneic haematopoietic stem cell transplantation

    PubMed Central

    Alousi, Amin; Ghosh, Somnath; Rice, David; Moran, Cesar; Manning, John T; Iliescu, Cesar; Hymes, Sharon; Kim, Stella; Bashoura, Lara; Kornblau, Steven; Dickey, Burton F

    2011-01-01

    Chronic graft-versus-host disease (GVHD) is a common complication of allogeneic haematopoietic cell transplantation, with pulmonary involvement occurring in 5–10% of cases. Obliterative bronchiolitis (OB) is recognised as a diagnostic manifestation of chronic GVHD, whereas lymphocytic interstitial pneumonitis (LIP) has been reported but is not considered diagnostic, and pleuritis is not clearly associated. The authors describe a transplant patient who simultaneously manifested three distinct pulmonary processes: OB, patchy LIP and pleuropericarditis. The onset of these entities along with other manifestations of chronic GVHD, their resolution with increased immunosuppression and their recurrence upon tapering support all three entities as manifestations of GVHD in the lungs. PMID:22707568

  4. Pleuropericarditis, obliterative bronchiolitis and lymphocytic interstitial pneumonitis after allogeneic haematopoietic stem cell transplantation.

    PubMed

    Alousi, Amin; Ghosh, Somnath; Rice, David; Moran, Cesar; Manning, John T; Iliescu, Cesar; Hymes, Sharon; Kim, Stella; Bashoura, Lara; Kornblau, Steven; Dickey, Burton F

    2011-02-23

    Chronic graft-versus-host disease (GVHD) is a common complication of allogeneic haematopoietic cell transplantation, with pulmonary involvement occurring in 5-10% of cases. Obliterative bronchiolitis (OB) is recognised as a diagnostic manifestation of chronic GVHD, whereas lymphocytic interstitial pneumonitis (LIP) has been reported but is not considered diagnostic, and pleuritis is not clearly associated. The authors describe a transplant patient who simultaneously manifested three distinct pulmonary processes: OB, patchy LIP and pleuropericarditis. The onset of these entities along with other manifestations of chronic GVHD, their resolution with increased immunosuppression and their recurrence upon tapering support all three entities as manifestations of GVHD in the lungs.

  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. Hypersensitivity to laminaria: a case report and review of literature.

    PubMed

    Sierra, Tania; Figueroa, Melissa M; Chen, Katherine T; Lunde, Britt; Jacobs, Adam

    2015-04-01

    We report a case of laminaria hypersensitivity treated with diphenhydramine and corticosteroids. A literature review identified 10 previously reported cases, with 8 recognized as anaphylaxis, and good outcomes with corticosteroids and antihistamines despite limited epinephrine utilization. Laminaria hypersensitivity is likely IgE mediated with an increased anaphylaxis risk with prior exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. 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.

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

    PubMed Central

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

    2015-01-01

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

  9. Radiocontrast media hypersensitivity in the Asia Pacific region.

    PubMed

    Lee, Suh-Young; Lim, Kyoung-Whan; Chang, Yoon-Seok

    2014-04-01

    Radiocontrast media (RCM) is a major cause of drug hypersensitivity reactions as the medical application of RCM is increasing recently. RCM induced hypersensitivity reactions are considered as unpredictable type B reactions. Underlying mechanism of RCM induced hypersensitivity was previously regarded as nonimmunological mechanisms but recent studies suggest that immunological mechanisms could also be involved. As a result, the roles of skin tests and premedication are revisiting. As there has been no report that comprehensively summarized and analyzed the results of the studies on RCM hypersensitivity in the Asia Pacific region, we aimed to review the literatures on hypersensitivity reactions to RCM in terms of prevalence clinical manifestations, diagnostic approach, and preventive measures in the Asia Pacific region.

  10. Radiocontrast media hypersensitivity in the Asia Pacific region

    PubMed Central

    Lee, Suh-Young; Lim, Kyoung-Whan

    2014-01-01

    Radiocontrast media (RCM) is a major cause of drug hypersensitivity reactions as the medical application of RCM is increasing recently. RCM induced hypersensitivity reactions are considered as unpredictable type B reactions. Underlying mechanism of RCM induced hypersensitivity was previously regarded as nonimmunological mechanisms but recent studies suggest that immunological mechanisms could also be involved. As a result, the roles of skin tests and premedication are revisiting. As there has been no report that comprehensively summarized and analyzed the results of the studies on RCM hypersensitivity in the Asia Pacific region, we aimed to review the literatures on hypersensitivity reactions to RCM in terms of prevalence clinical manifestations, diagnostic approach, and preventive measures in the Asia Pacific region. PMID:24809018

  11. The prevalence of widespread central hypersensitivity in chronic pain patients.

    PubMed

    Schliessbach, J; Siegenthaler, A; Streitberger, K; Eichenberger, U; Nüesch, E; Jüni, P; Arendt-Nielsen, L; Curatolo, M

    2013-11-01

    Chronic pain is associated with generalized hypersensitivity and impaired endogenous pain modulation (conditioned pain modulation; CPM). Despite extensive research, their prevalence in chronic pain patients is unknown. This study investigated the prevalence and potential determinants of widespread central hypersensitivity and described the distribution of CPM in chronic pain patients. We examined 464 consecutive chronic pain patients for generalized hypersensitivity and CPM using pressure algometry at the second toe and cold pressor test. Potential determinants of generalized central hypersensitivity were studied using uni- and multivariate regression analyses. Prevalence of generalized central hypersensitivity was calculated for the 5th, 10th and 25th percentile of normative values for pressure algometry obtained by a previous large study on healthy volunteers. CPM was addressed on a descriptive basis, since normative values are not available. Depending on the percentile of normative values considered, generalized central hypersensitivity affected 17.5-35.3% of patients. 23.7% of patients showed no increase in pressure pain threshold after cold pressor test. Generalized central hypersensitivity was more frequent and CPM less effective in women than in men. Unclearly classifiable pain syndromes showed higher frequencies of generalized central hypersensitivity than other pain syndromes. Although prevalent in chronic pain, generalized central hypersensitivity is not present in every patient. An individual assessment is therefore required in order to detect altered pain processing. The broad basic knowledge about central hypersensitivity now needs to be translated into concrete clinical consequences, so that patients can be offered an individually tailored mechanism-based treatment. © 2013 European Federation of International Association for the Study of Pain Chapters.

  12. Stress induces transient auditory hypersensitivity in rats.

    PubMed

    Mazurek, Birgit; Haupt, Heidemarie; Joachim, Ricarda; Klapp, Burghard F; Stöver, Timo; Szczepek, Agnieszka J

    2010-01-01

    Exposure to harsh environment induces stress reactions that increase probability of survival. Stress influences the endocrine, nervous and immune systems and affects the functioning of a variety of organs. Numerous researchers demonstrated that a 24-h exposure to an acoustic rodent repellent provokes stress reaction in exposed animals. In addition to the activated hypothalamic-pituitary-adrenal (HPA) axis, exposed animals had pathological reactions in the reproductive organs, bronchia and skin. Here, we examined the effect of above stress model on the auditory system of Wistar rats. We found that 24-h stress decreases the thresholds and increases the amplitudes of auditory brainstem responses and distortion product otoacoustic emissions. Resultant auditory hypersensitivity was transient and most pronounced between 3 and 6h post-stress, returning to control levels one week later. The concentration of corticosterone and tumor necrosis factor alpha was systemically elevated in stressed animals between 3 and 6h post-stress, confirming the activation of the HPA axis. In addition, expression of the HPA-axis-associated genes: glucocorticoid receptor (GR) and hypoxia-inducible factor 1 alpha (Hif1a) was modulated in the auditory tissues. In detail, in the inferior colliculus, we found an up-regulation of GR mRNA 3h post-stress and continuous up-regulation of Hif1a up to 24h post-stress. In the spiral ganglion, we found no differences in gene expression between stressed and control animals. In the organ of Corti, expression of GR mRNA remained stable, whereas that of Hif1a was significantly down-regulated one week after stress. In addition, the expression of an outer hair cell marker prestin was significantly up-regulated 6h post-stress. We conclude that 24-h stress induces transient hypersensitivity of the auditory system and modulates gene expression in a tissue-specific manner. Stress-induced auditory hypersensitivity could have evolutionary consequence by giving animals

  13. Inhaled Liposomal Ciprofloxacin Protects against a Lethal Infection in a Murine Model of Pneumonic Plague

    PubMed Central

    Hamblin, Karleigh A.; Armstrong, Stuart J.; Barnes, Kay B.; Davies, Carwyn; Laws, Thomas; Blanchard, James D.; Harding, Sarah V.; Atkins, Helen S.

    2017-01-01

    Inhalation of Yersinia pestis can lead to pneumonic plague, which without treatment is inevitably fatal. Two novel formulations of liposome-encapsulated ciprofloxacin, ‘ciprofloxacin for inhalation’ (CFI, Lipoquin®) and ‘dual release ciprofloxacin for inhalation’ (DRCFI, Pulmaquin®) containing CFI and ciprofloxacin solution, are in development. These were evaluated as potential therapies for infection with Y. pestis. In a murine model of pneumonic plague, human-like doses of aerosolized CFI, aerosolized DRCFI or intraperitoneal (i.p.) ciprofloxacin were administered at 24 h (representing prophylaxis) or 42 h (representing treatment) post-challenge. All three therapies provided a high level of protection when administered 24 h post-challenge. A single dose of CFI, but not DRCFI, significantly improved survival compared to a single dose of ciprofloxacin. Furthermore, single doses of CFI and DRCFI reduced bacterial burden in lungs and spleens to below the detectable limit at 60 h post-challenge. When therapy was delayed until 42 h post-challenge, a single dose of CFI or DRCFI offered minimal protection. However, single doses of CFI or DRCFI were able to significantly reduce the bacterial burden in the spleen compared to empty liposomes. A three-day treatment regimen of ciprofloxacin, CFI, or DRCFI resulted in high levels of protection (90–100% survival). This study suggests that CFI and DRCFI may be useful therapies for Y. pestis infection, both as prophylaxis and for the treatment of plague. PMID:28220110

  14. [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.

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

    PubMed

    Eddy, Justin L; Schroeder, Jay A; Zimbler, Daniel L; Bellows, Lauren E; Lathem, Wyndham W

    2015-12-01

    Many pathogens usurp the host hemostatic system during infection to promote pathogenesis. Yersinia pestis, the causative agent of plague, expresses the plasminogen activator protease Pla, which has been shown in vitro to target and cleave multiple proteins within the fibrinolytic pathway, including the plasmin inhibitor α2-antiplasmin (A2AP). It is not known, however, if Pla inactivates A2AP in vivo; the role of A2AP during respiratory Y. pestis infection is not known either. Here, we show that Y. pestis does not appreciably cleave A2AP in a Pla-dependent manner in the lungs during experimental pneumonic plague. Furthermore, following intranasal infection with Y. pestis, A2AP-deficient mice exhibit no difference in survival time, bacterial burden in the lungs, or dissemination from wild-type mice. Instead, we found that in the absence of Pla, A2AP contributes to the control of the pulmonary inflammatory response during infection by reducing neutrophil recruitment and cytokine production, resulting in altered immunopathology of the lungs compared to A2AP-deficient mice. Thus, our data demonstrate that A2AP is not significantly affected by the Pla protease during pneumonic plague, and although A2AP participates in immune modulation in the lungs, it has limited impact on the course or ultimate outcome of the infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. 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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Respiratory syncytial virus pneumonitis in immunocompromised adults: clinical features and outcome.

    PubMed

    Ebbert, Jon O; Limper, Andrew H

    2005-01-01

    Though predominantly an infection of children, respiratory syncytial virus (RSV) also infects adults, particularly those with immune compromise. To define the clinical spectrum and impact of RSV pneumonitis on hospitalized, immunocompromised adults. Retrospective chart review. Clinical parameters including premorbid conditions, presentation, radiologic findings, treatment and outcome were examined in a consecutive patients series from an inpatient tertiary-care center. Eleven immunocompromised adults who had undergone bronchoalveolar lavage (BAL) between January 1987 and December 1996 and who had culture-verified RSV pneumonitis were evaluated. This series consisted primarily of patients undergoing chemotherapy or bone marrow transplantation for lymphoma or leukemia. Two were immunosuppressed due to high-dose corticosteroids. A majority (91%) were admitted between November and May, with dyspnea and productive cough. In contrast to earlier studies, there was a paucity of upper respiratory infection symptoms (i.e. sinus congestion, sore throat) and a preponderance of lower respiratory physical exam findings (i.e. wheezing, bibasilar rales). Patients were typically hypoxemic and febrile prior to BAL. Eight demonstrated co-isolates of bacterial or fungi on BAL. The chest radiographs generally revealed diffuse patchy infiltrates, including alveolar opacities. Histology demonstrated diffuse alveolar damage, bronchiolitis with organizing pneumonia, and hyaline membrane formation. Over half required intubation, and 55% died. Although ribavirin therapy may be beneficial in some intubated patients, its overall efficacy cannot be established from this series. RSV is a serious cause of morbidity and mortality in immunocompromised adults. Further development and implementation of an effective vaccine and additional therapeutic interventions are needed.

  18. [A case of interstitial pneumonitis caused by inhalation of cadmium fumes].

    PubMed

    Inoue, S; Suzumura, Y; Takahashi, K

    1994-09-01

    A 48-year-old man who had been a welder for 25 years was admitted to our hospital on February 18, 1990 for investigation of a diffuse bilateral lung shadow that had a ground-glass appearance. On the day of admission, he had been welding copper water supply pipe and used silver brazing with an oxyacetylene torch. After almost 7 hours of work, he had a chill, high fever, and dyspnea. Blood gas analysis revealed severe hypoxemia (PaO2 34.5 Torr, PaCO2 29.4 Torr). The level of copper in serum was slightly higher than normal (174 micrograms/dl). A transbronchial lung biopsy specimen showed lymphocyte infiltration and fibrous changes of the alveolar walls, which seemed to be granulomatous pneumonitis. Steroid therapy was effective against the symptoms, and the radiographic findings also improved. We think this is a rare case of interstitial pneumonitis caused by inhalation of cadmium fumes contained in silver brazing.

  19. Administration of a Synthetic TLR4 Agonist Protects Mice from Pneumonic Tularemia1

    PubMed Central

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

    2011-01-01

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

  20. 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

  1. 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.

  2. Selective immediate hypersensitivity reactions to NSAIDs.

    PubMed

    Canto, Maria Gabriela; Andreu, Isabel; Fernandez, Javier; Blanca, Miguel

    2009-08-01

    Selective immediate reactions to NSAIDs imply that patients develop a urticarial/anaphylactic response to a single drug with good tolerance to other compounds. No systematic review of these reactions has yet been made. With the increase in consumption of NSAIDs, these have become one of the most common drugs inducing hypersensitivity reactions. Although cross-intolerance reactions are the most common, a significant proportion is selective responses. As specific IgE antibodies are not always found, there is only indirect evidence supporting an IgE-mediated mechanism in selective NSAID reactors. Selective immediate reactions to NSAIDs must be considered when a patient develops urticaria or anaphylaxis after intake of one drug with good tolerance to drugs from other groups or even a drug from the same group with a slightly different chemical structure. Further research is required to identify the antigenic determinant structures recognized.

  3. Hypersensitivity to Ticks and Lyme Disease Risk

    PubMed Central

    Burke, Georgine; Wikel, Stephen K.; Spielman, Andrew; Telford, Sam R.; McKay, Kathleen

    2005-01-01

    Although residents of Lyme disease–endemic regions describe frequent exposure to ticks, Lyme disease develops in relatively few. To determine whether people who experience cutaneous hypersensitivity against tick bite have fewer episodes of Lyme disease than those who do not, we examined several factors that might restrict the incidence of Lyme disease among residents of Block Island, Rhode Island. Of 1,498 study participants, 27% (95% confidence interval [CI] 23%–31%) reported >1 tick bites, and 17% (95% CI 13%–21%) reported itch associated with tick bite in the previous year. Borrelia burgdorferi infected 23% (95% CI 20%–26%) of 135 nymphal Ixodes scapularis (I. dammini) ticks. The likelihood of Lyme disease infection decreased with >3 reports of tick-associated itch (odds ratio 0.14, 95% CI 0.94–0.03, p = 0.01). Prior exposure to uninfected vector ticks protects residents of disease-endemic sites from Lyme disease. PMID:15705320

  4. Antibiotic hypersensitivity reactions and approaches to desensitization.

    PubMed

    Legendre, Davey P; Muzny, Christina A; Marshall, Gailen D; Swiatlo, Edwin

    2014-04-01

    Before initiating antibiotic therapy, drug hypersensitivity is an important consideration, and a common strategy is to avoid giving patients medications when a high likelihood of severe reactions exists. With an increase in antibiotic resistance and a decrease in novel antibiotics, there is greater pressure to consider antibiotics in patients with a history of adverse reactions. The major concerns include IgE-mediated, or type I, reactions, anaphylaxis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Some antibiotics with similar characteristics, such as cephalosporins and penicillins, may be given safely to patients with a certain allergy profile. There is still greater concern when considering antibiotics for patients with reported allergy. Desensitization is a strategy to safely induce drug tolerance to a specific drug to limit the possibility of a type I reaction.

  5. 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.

  6. Squid hypersensitivity: a clinical and immunologic study.

    PubMed

    Carrillo, T; Castillo, R; Caminero, J; Cuevas, M; Rodriguez, J C; Acosta, O; Rodriguez de Castro, F

    1992-06-01

    Hypersensitivity to mollusk has rarely been described in the literature. Among the mollusks, the cephalopods are a group of great importance as a food source. We report seven patients who had had symptoms highly suggestive of IgE-mediated reactions after ingesting squid or inhaling vapors from cooking squid. All had previously suffered from persistent rhinitis or asthma for years. In addition, six of the seven patients had had symptoms after ingesting shrimp. Skin prick tests were strongly positive for boiled squid extract and for various commercial crustacean extracts. Specific IgE antibodies against boiled extract and several crustacean extracts were demonstrated in all patients by RAST and reverse enzyme immunoassay. Cross reactivity between squid and shrimp and other crustaceans was demonstrated by reverse immunoassay inhibition studies. Cross reactivity could not be demonstrated between squid and octopus, which are both cephalopods, nor between squid and other mollusks.

  7. Hypersensitivity to ticks and Lyme disease risk.

    PubMed

    Burke, Georgine; Wikel, Stephen K; Spielman, Andrew; Telford, Sam R; McKay, Kathleen; Krause, Peter J

    2005-01-01

    Although residents of Lyme disease-endemic regions describe frequent exposure to ticks, Lyme disease develops in relatively few. To determine whether people who experience cutaneous hypersensitivity against tick bite have fewer episodes of Lyme disease than those who do not, we examined several factors that might restrict the incidence of Lyme disease among residents of Block Island, Rhode Island. Of 1,498 study participants, 27% (95% confidence interval [CI] 23%-31%) reported > or = 1 tick bites, and 17% (95% CI 13%-21%) reported itch associated with tick bite in the previous year. Borrelia burgdorferi infected 23% (95% CI 20%-26%) of 135 nymphal Ixodes scapularis (I. dammini) ticks. The likelihood of Lyme disease infection decreased with >3 reports of tick-associated itch (odds ratio 0.14, 95% CI 0.94-0.03, p = 0.01). Prior exposure to uninfected vector ticks protects residents of disease-endemic sites from Lyme disease.

  8. [Hypersensitivity reaction to radio contrast media: diagnosis, prevention and treatment].

    PubMed

    Mahlab-Guri, Keren; Herskovitz, Pearl; Sthoeger, Zev

    2012-07-01

    More than 70 million radiographic examinations with radio contrast media are performed worldwide each year. The incidence of adverse reactions to radio contrast media is 5-13%. Adverse reactions include hypersensitivity reactions, chemotoxic reactions and renal toxicity. Hypersensitivity reactions to radio contrast media range from mild pruritus to life-threatening emergency. The differential diagnosis between hypersensitivity reaction to radio contrast media and chemotoxic reaction is challenging. The incidence of chemotoxic reactions is mainly affected by the chemical structure of the radio contrast media and the rate of infusion. The incidence of hypersensitivity radio contrast media reaction is affected by age and by the presence of asthma and other atopic diseases. The diagnosis of hypersensitivity reaction to radio contrast media is based on clinical manifestations. The additional value of laboratory tests is limited and questionable. In case of hypersensitivity radio contrast reaction, the infusion should be stopped immediately, airways should be protected and fluids, oxygen and drugs should be given. Prophylactic treatment before its administration may prevent hypersensitivity reactions to radio contrast media.

  9. Shoulder arthroplasty in the patient with metal hypersensitivity.

    PubMed

    Morwood, Michael P; Garrigues, Grant E

    2015-07-01

    The in vivo effects of metal hypersensitivity remain a topic of much debate. At the core of this debate is the possible, although still hotly contested, link between metal hypersensitivity and poorly functioning or failing implants. There are multiple studies on this topic in the hip and knee arthroplasty literature, but the applicability of this experience to shoulder arthroplasty remains unclear. Although how often metal hypersensitivity affects shoulder arthroplasty patients remains uncertain, a multitude of case reports have implicated metallic implants as a source of local and systemic allergic reactions. We recommend a cautious approach to patients with a history of metal hypersensitivity, including a careful evaluation of suspected metal hypersensitivities in all patients undergoing shoulder arthroplasty. If available, we recommend a metallic implant with low to no nickel content in patients with metal hypersensitivity. Given the large and increasing, number of total shoulder arthroplasty procedures and the high percentage of the population having a known or suspected metal hypersensitivity, this review is intended to guide and educate the shoulder surgeon in the evaluation and treatment of this patient population and to point out the areas where evidence-based recommendations are lacking. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  10. Availability of Total Knee Arthroplasty Implants for Metal Hypersensitivity Patients

    PubMed Central

    Ajwani, Sanil Harji; Charalambous, Charalambos P.

    2016-01-01

    Purpose To provide information on the type of “hypersensitivity-friendly” components available for primary total knee arthroplasty (TKA) in the current market. Materials and Methods Implant manufactures were identified using the 2013 National Joint Registries of the United Kingdom and Sweden and contacted to obtain information about the products they offer for patients with metal hypersensitivity. Results Information on 23 TKA systems was provided by 13 implant manufacturers. Of these, 15 systems had options suitable for metal hypersensitivity patients. Two types of “hypersensitivity-friendly” components were identified: 10 implants were cobalt chrome prostheses with a “hypersensitivity-friendly” outer coating and 5 implants were made entirely from non-cobalt chrome alloys. Conclusions The results of this study suggest that several hypersensitivity TKA options exist, some of which provide the same designs and surgical techniques as the conventional implants. The information in this study can guide TKA surgeons in making informed choices about implants and identifying implants that could be examined in future controlled studies comparing outcomes between “hypersensitivity-friendly” and conventional implants. PMID:27894179

  11. Immediate hypersensitivity reaction to gadolinium-based MR contrast media.

    PubMed

    Jung, Jae-Woo; Kang, Hye-Ryun; Kim, Min-Hye; Lee, Whal; Min, Kyung-Up; Han, Moon-Hee; Cho, Sang-Heon

    2012-08-01

    To determine the incidence and risk factors of immediate hypersensitivity reactions to gadolinium-based magnetic resonance (MR) contrast agents. Institutional review board approval and a waiver of informed consent were obtained. A retrospective study of patients who had been given gadolinium-based MR contrast media between August 2004 and July 2010 was performed by reviewing their electronic medical records. In addition to data on immediate hypersensitivity reaction, the kinds of MR contrast media and demographic data including age, sex, and comorbidity were collected. To compare the groups, the χ(2) test, Fisher exact test, χ(2) test for trend, Student t test, analysis of variance test, and multiple logistic regression test were performed. A total of 112 immediate hypersensitivity reactions (0.079% of 141 623 total doses) were identified in 102 patients (0.121% of 84 367 total patients). Among the six evaluated MR contrast media, gadodiamide had the lowest rate (0.013%) of immediate hypersensitivity reactions, while gadobenate dimeglumine had the highest rate (0.22%). The rate for immediate hypersensitivity reactions was significantly higher in female patients (odds ratio = 1.687; 95% confidence interval: 1.143, 2.491) and in patients with allergies and asthma (odds ratio = 2.829; 95% confidence interval: 1.427, 5.610). Patients with a previous history of immediate hypersensitivity reactions had a higher rate of recurrence after reexposure to MR contrast media (30%) compared with the incidence rate in total patients (P < .0001). The incidence of immediate hypersensitivity reactions increased depending on the number of times patients were exposed to MR contrast media (P for trend = .036). The most common symptom was urticaria (91.1%), and anaphylaxis occurred in 11 cases (9.8%). The mortality rate was 0.0007% because of one fatality. The incidence of immediate hypersensitivity reactions to MR contrast media was 0.079%, and the recurrence rate of hypersensitivity

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  14. [Causes and treatment of hypersensitivity in tooth root].

    PubMed

    Skaleric, U; Petelin, M

    1989-01-01

    The review article describes aetiology and treatment of dental root hypersensitivity. The three main theories of pain transduction from the exposed dentin surface to pain receptors in dental pulp are described. In addition, therapeutic compounds used to stimulate reparatory dentin formation and mineralization of peritubular dentin are described as well. The application of resins and adhesives on exposed dentin root surfaces is advocated in cases of chronic hypersensitivity. Finally, the authors emphasize the need for correct oral hygiene and early orthodontic treatment, if indicated, to prevent gingival recession and hypersensitivity of exposed root surfaces.

  15. Outpatient desensitization in selected patients with platinum hypersensitivity reactions.

    PubMed

    O'Malley, David M; Vetter, Monica Hagan; Cohn, David E; Khan, Ambar; Hays, John L

    2017-06-01

    Platinum-based chemotherapies are a standard treatment for both initial and recurrent gynecologic cancers. Given this widespread use, it is important to be aware of the features of platinum hypersensitivity reactions and the subsequent treatment of these reactions. There is also increasing interest in the development of desensitization protocols to allow patients with a history of platinum hypersensitivity to receive further platinum based therapy. In this review, we describe the management of platinum hypersensitivity reactions and the desensitization protocols utilized at our institution. We also describe the clinical categorizations utilized to triage patients to appropriate desensitization protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Role of Delayed Hypersensitivity in Blastomycosis of Mice

    PubMed Central

    Spencer, Harry D.; Cozad, George C.

    1973-01-01

    C57BL/6J mice rendered hypersensitive to Blastomyces dermatitidis were protected from the lethal effects of a blastomyces infection. This protection was observed following a lethal intraperitoneal challenge with viable cells 15 days after subcutaneous inoculation with 3.9 × 104 viable cells. Delayed hypersensitivity was induced in C57 mice by two injections of Merthiolate-killed cells in adjuvant or by a single injection of viable cells. Development of hypersensitivity was determined at appropriate intervals by footpad injection with killed yeast cells. PMID:4713689

  17. Intestinal B cell-activating factor: an indicator of non-IgE-mediated hypersensitivity reactions to food?

    PubMed

    Lied, G Arslan; Lillestøl, K; Valeur, J; Berstad, A

    2010-07-01

    Medically confirmed hypersensitivity reactions to food are usually IgE-mediated. Non-IgE-mediated reactions are not only seldom recognized but also more difficult to diagnose. To examine B cell-activating factor (BAFF) in serum and gut lavage fluid of patients with self-reported food hypersensitivity, and to study its relationship to atopic disease. Gut lavage fluid was obtained from 60 and serum from another 17 patients with self-reported food hypersensitivity. Twenty healthy volunteers served as controls, gut lavage fluid was obtained in all, serum from 11 of 20. The patients were divided into atopic and non-atopic subgroups. BAFF was measured by ELISA in both serum and gut lavage fluid. B cell-activating factor levels in serum and gut lavage fluid were significantly higher in patients than in controls (P < 0.03 and P < 0.002 respectively). Non-atopic patients had significantly higher levels of BAFF in serum than both atopic patients (P < 0.05) and controls (P < 0.05). There was no significant correlation between serum levels of BAFF and IgE. The results suggest that BAFF might be a new mediating mechanism in food hypersensitivity reactions. Significantly higher levels in non-atopic compared with atopic patients, and no correlation between BAFF and IgE, suggest that BAFF might be involved particularly in non-IgE-mediated reactions.

  18. Development of the Sensory Hypersensitivity Scale (SHS): a self-report tool for assessing sensitivity to sensory stimuli.

    PubMed

    Dixon, Eric A; Benham, Grant; Sturgeon, John A; Mackey, Sean; Johnson, Kevin A; Younger, Jarred

    2016-06-01

    Sensory hypersensitivity is one manifestation of the central sensitization that may underlie conditions such as fibromyalgia and chronic fatigue syndrome. We conducted five studies designed to develop and validate the Sensory Hypersensitive Scale (SHS); a 25-item self-report measure of sensory hypersensitivity. The SHS assesses both general sensitivity and modality-specific sensitivity (e.g. touch, taste, and hearing). 1202 participants (157 individuals with chronic pain) completed the SHS, which demonstrated an adequate overall internal reliability (Cronbach's alpha) of 0.81, suggesting the tool can be used as a cross-modality assessment of sensitivity. SHS scores demonstrated only modest correlations (Pearson's r) with depressive symptoms (0.19) and anxiety (0.28), suggesting a low level of overlap with psychiatric complaints. Overall SHS scores showed significant but relatively modest correlations (Pearson's r) with three measures of sensory testing: cold pain tolerance (-0.34); heat pain tolerance (-0.285); heat pain threshold (-0.271). Women reported significantly higher scores on the SHS than did men, although gender-based differences were small. In a chronic pain sample, individuals with fibromyalgia syndrome demonstrated significantly higher SHS scores than did individuals with osteoarthritis or back pain. The SHS appears suitable as a screening measure for sensory hypersensitivity, though additional research is warranted to determine its suitability as a proxy for central sensitization.

  19. 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.

  20. Ladybug hypersensitivity among residents of homes infested with ladybugs in Kentucky.

    PubMed

    Sharma, Kusum; Muldoon, Susan B; Potter, Michael F; Pence, Hobert L

    2006-10-01

    There have been isolated case reports of hypersensitivity to the ladybug species Harmonia axyridis. Entomologists now report a rapid increase in ladybug numbers, giving rise to increasing complaints of residential infestations. To determine whether ladybug infestation of homes causes hypersensitivity among residents and to estimate the prevalence of self-reported ladybug allergy in this population. This pilot observational study was conducted using an anonymous survey. The participation rate was 59% (99/167). The incidence of self-reported allergy symptoms in this population was 77% (95% confidence interval [CI], 67%-85%). The prevalence of self-reported ladybug allergy was 50% (95% CI, 39%-60%). Of all the respondents, 19% (95% CI, 12%-28%) reported allergy symptoms on direct contact with ladybugs and 31% (95% CI, 22%-41%) reported the use of extra allergy medications during times of infestation. The correlation between worsening of allergy symptoms and time of infestation was significant for spring, fall, and winter infestations (P = .02, P = .001, and P < .001, respectively). To our knowledge, this is the first study to estimate the prevalence of ladybug hypersensitivity, which was found to be 50% by self-report among people with home infestations. These results suggest that the ladybug could be a significant cause of respiratory allergy in heavily infested homes. Further studies using diagnostic testing to confirm allergy are now indicated. We recommend that patients with spring, fall, and winter allergies be asked about ladybug infestation and that ladybug reagents be made available for diagnostic testing.

  1. Pneumonic Plague

    MedlinePlus

    ... Training Related Bioterrorism Resources Bacillus anthracis (Anthrax) Botulism (Clostridium botulinum toxin) Brucella species (brucellocis) Laboratory Information Surveillance & Investigation Burkholderia mallei (glanders) ...

  2. Chemical pneumonitis

    MedlinePlus

    ... chemicals. Alternative Names Aspiration pneumonia - chemical Images Lungs Respiratory system References Blanc PD. Acute responses to toxic exposures. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray and Nadel's Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: ...

  3. 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

  4. Development and validation of the Drug Hypersensitivity Quality of Life Questionnaire.

    PubMed

    Baiardini, Ilaria; Braido, Fulvio; Fassio, Omar; Calia, Rosaria; Giorgio, Walter Canonica; Canonica, Giorgio Walter; Romano, Antonino

    2011-04-01

    The impact of drug hypersensitivity has never been considered from the patient's perspective, and no questionnaire is currently available for this purpose. To develop and validate a questionnaire specifically designed for the assessment of quality of life in patients with drug hypersensitivity entitled the Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q). During the development procedure, an initial questionnaire of 34 items was generated and administered to 70 patients; the 20 most important items were detected and converted into questions evaluated with a 5-point Likert scale. This provisional questionnaire then underwent a validation procedure to assess its psychometric properties. The DrHy-Q and the Psychological General Well-Being Index (PGWBI) were completed by 365 patients (67.5% female; mean [SD] age, 40 [15] years). Statistical analysis revealed a 1-dimensional structure for the DrHy-Q that explained up to 50.7% of the total variance and showed good levels of internal consistency for the extracted factor (Cronbach α = 0.928). The correlations between the DrHy-Q and the PGWBI scores were low. However, the DrHy-Q scores of patients who experienced anaphylactic shock were significantly higher than the scores from patients with other reactions (analysis of variance; F = 5.991; df = 4; P < .001). The test-retest associations were good (R = 0.995; P < .001). DrHy-Q met the standards for construct validity, internal consistency, and reliability, indicating that it is appropriate for use alone or in combination with other patient-reported outcome questionnaires to explore the subjective experiences of patients with drug hypersensitivity. Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Occupational trichloroethylene hypersensitivity syndrome: human herpesvirus 6 reactivation and rash phenotypes.

    PubMed

    Kamijima, Michihiro; Wang, Hailan; Yamanoshita, Osamu; Ito, Yuki; Xia, Lihua; Yanagiba, Yukie; Chen, Cishan; Okamura, Ai; Huang, Zhenlie; Qiu, Xinxiang; Song, Xiangrong; Cai, Tingfeng; Liu, Lili; Ge, Yichen; Deng, Yingyu; Naito, Hisao; Yoshikawa, Tetsushi; Tohyama, Mikiko; Li, Laiyu; Huang, Hanlin; Nakajima, Tamie

    2013-12-01

    Trichloroethylene (TCE) is an industrial solvent which can cause severe generalized dermatitis, i.e., occupational TCE hypersensitivity syndrome. Reactivation of latent human herpesvirus 6 (HHV6) can occur in such patients, which has made TCE known as a causative chemical of drug-induced hypersensitivity syndrome (DIHS). This study aimed to clarify HHV6 status, cytokine profiles and their association with rash phenotypes in patients with TCE hypersensitivity syndrome. HHV6 DNA copy numbers, anti-HHV6 antibody titers, and cytokines were measured in blood prospectively sampled 5-7 times from 28 hospitalized patients with the disease. The patients (19 had exfoliative dermatitis (ED) and 9 had non-ED type rash) generally met the diagnostic criteria for DIHS. Viral reactivation defined as increases in either HHV6 DNA (≥100 genomic copies/10(6) peripheral blood mononuclear cells) or antibody titers was identified in 24 (89%) patients. HHV6 DNA, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-5, IL-6 and IL-10 concentrations were remarkably higher in the patients than in the healthy workers (p<0.01). Positive correlations between HHV6 DNA, TNF-α, IFN-γ, IL-6 and IL-10 were significant (p<0.05) except for that between HHV6 DNA and IFN-γ. An increase in HHV6 DNA was positively associated with an increase in TNF-α on admission (p<0.01). HHV6 DNA, the antibody titers, TNF-α and IL-10 concentrations were significantly higher in ED than in the non-ED type (p<0.05). Reactivated HHV6 and the increased cytokines could be biomarkers of TCE hypersensitivity syndrome. The higher-level reactivation and stronger humoral responses were associated with ED-type rash. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Cognitive and neurobiological alterations in electromagnetic hypersensitive patients: results of a case-control study.

    PubMed

    Landgrebe, M; Frick, U; Hauser, S; Langguth, B; Rosner, R; Hajak, G; Eichhammer, P

    2008-12-01

    Hypersensitivity to electromagnetic fields (EMF) is frequently claimed to be linked to a variety of non-specific somatic and neuropsychological complaints. Whereas provocation studies often failed to demonstrate a causal relationship between EMF exposure and symptom formation, recent studies point to a complex interplay of neurophysiological and cognitive alterations contributing to symptom manifestation in electromagnetic hypersensitive patients (EHS). However, these studies have examined only small sample sizes or have focused on selected aspects. Therefore this study examined in the largest sample of EHS EMF-specific cognitive correlates, discrimination ability and neurobiological parameters in order to get further insight into the pathophysiology of electromagnetic hypersensitivity. In a case-control design 89 EHS and 107 age- and gender-matched controls were included in the study. Health status and EMF-specific cognitions were evaluated using standardized questionnaires. Perception thresholds following single transcranial magnetic stimulation (TMS) pulses to the dorsolateral prefrontal cortex were determined using a standardized blinded measurement protocol. Cortical excitability parameters were measured by TMS. Discrimination ability was significantly reduced in EHS (only 40% of the EHS but 60% of the controls felt no sensation under sham stimulation during the complete series), whereas the perception thresholds for real magnetic pulses were comparable in both groups (median 21% versus 24% of maximum pulse intensity). Intra-cortical facilitation was decreased in younger and increased in older EHS. In addition, typical EMF-related cognitions (aspects of rumination, symptom intolerance, vulnerability and stabilizing self-esteem) specifically differentiated EHS from their controls. These results demonstrate significant cognitive and neurobiological alterations pointing to a higher genuine individual vulnerability of electromagnetic hypersensitive patients.

  7. Giardia duodenalis induces paracellular bacterial translocation and causes postinfectious visceral hypersensitivity

    PubMed Central

    Halliez, Marie C. M.; Motta, Jean-Paul; Feener, Troy D.; Guérin, Gaetan; LeGoff, Laetitia; François, Arnaud; Colasse, Elodie; Favennec, Loic; Gargala, Gilles; Lapointe, Tamia K.; Altier, Christophe

    2016-01-01

    Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder. It is characterized by abdominal hypersensitivity, leading to discomfort and pain, as well as altered bowel habits. While it is common for IBS to develop following the resolution of infectious gastroenteritis [then termed postinfectious IBS (PI-IBS)], the mechanisms remain incompletely understood. Giardia duodenalis is a cosmopolitan water-borne enteropathogen that causes intestinal malabsorption, diarrhea, and postinfectious complications. Cause-and-effect studies using a human enteropathogen to help investigate the mechanisms of PI-IBS are sorely lacking. In an attempt to establish causality between giardiasis and postinfectious visceral hypersensitivity, this study describes a new model of PI-IBS in neonatal rats infected with G. duodenalis. At 50 days postinfection with G. duodenalis (assemblage A or B), long after the parasite was cleared, rats developed visceral hypersensitivity to luminal balloon distension in the jejunum and rectum, activation of the nociceptive signaling pathway (increased c-fos expression), histological modifications (villus atrophy and crypt hyperplasia), and proliferation of mucosal intraepithelial lymphocytes and mast cells in the jejunum, but not in the rectum. G. duodenalis infection also disrupted the intestinal barrier, in vivo and in vitro, which in turn promoted the translocation of commensal bacteria. Giardia-induced bacterial paracellular translocation in vitro correlated with degradation of the tight junction proteins occludin and claudin-4. The extensive observations associated with gut hypersensitivity described here demonstrate that, indeed, in this new model of postgiardiasis IBS, alterations to the gut mucosa and c-fos are consistent with those associated with PI-IBS and, hence, offer avenues for new mechanistic research in the field. PMID:26744469

  8. Giardia duodenalis induces paracellular bacterial translocation and causes postinfectious visceral hypersensitivity.

    PubMed

    Halliez, Marie C M; Motta, Jean-Paul; Feener, Troy D; Guérin, Gaetan; LeGoff, Laetitia; François, Arnaud; Colasse, Elodie; Favennec, Loic; Gargala, Gilles; Lapointe, Tamia K; Altier, Christophe; Buret, André G

    2016-04-15

    Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder. It is characterized by abdominal hypersensitivity, leading to discomfort and pain, as well as altered bowel habits. While it is common for IBS to develop following the resolution of infectious gastroenteritis [then termed postinfectious IBS (PI-IBS)], the mechanisms remain incompletely understood. Giardia duodenalis is a cosmopolitan water-borne enteropathogen that causes intestinal malabsorption, diarrhea, and postinfectious complications. Cause-and-effect studies using a human enteropathogen to help investigate the mechanisms of PI-IBS are sorely lacking. In an attempt to establish causality between giardiasis and postinfectious visceral hypersensitivity, this study describes a new model of PI-IBS in neonatal rats infected with G. duodenalis At 50 days postinfection with G. duodenalis (assemblage A or B), long after the parasite was cleared, rats developed visceral hypersensitivity to luminal balloon distension in the jejunum and rectum, activation of the nociceptive signaling pathway (increased c-fos expression), histological modifications (villus atrophy and crypt hyperplasia), and proliferation of mucosal intraepithelial lymphocytes and mast cells in the jejunum, but not in the rectum. G. duodenalis infection also disrupted the intestinal barrier, in vivo and in vitro, which in turn promoted the translocation of commensal bacteria. Giardia-induced bacterial paracellular translocation in vitro correlated with degradation of the tight junction proteins occludin and claudin-4. The extensive observations associated with gut hypersensitivity described here demonstrate that, indeed, in this new model of postgiardiasis IBS, alterations to the gut mucosa and c-fos are consistent with those associated with PI-IBS and, hence, offer avenues for new mechanistic research in the field. Copyright © 2016 the American Physiological Society.

  9. Stratified premedication strategy for the prevention of contrast media hypersensitivity in high-risk patients.

    PubMed

    Lee, Suh-Young; Yang, Min Suk; Choi, Young-Hoon; Park, Chang Min; Park, Heung-Woo; Cho, Sang Heon; Kang, Hye-Ryun

    2017-03-01

    Although the severity of hypersensitivity reactions to iodinated contrast media varies, it is well correlated with the severity of recurrent reactions; however, prophylaxis protocols are not severity-stratified. To assess the outcomes of tailored prophylaxis according to the severity of hypersensitivity reactions to iodinated contrast media. Our premedication protocols were stratified based on the severity of previous reactions: (1) 4 mg of chlorpheniramine for mild reactions, (2) adding 40 mg of methylprednisolone for moderate reactions, and (3) adding multiple doses of 40 mg of methylprednisolone for severe index reactions. Cases of reexposure in patients with a history of hypersensitivity reactions were routinely monitored and mandatorily recorded. Among a total of 850 patients who underwent enhanced computed tomography after severity-tailored prophylaxis, breakthrough reactions occurred in 17.1%, but most breakthrough reactions (89.0%) were mild and did not require medical treatment. Additional corticosteroid use did not reduce the breakthrough reaction rate in cases with a mild index reaction (16.8% vs 17.2%, P = .70). However, underpremedication with a single dose of corticosteroid revealed significantly higher rates of breakthrough reaction than did double doses of corticosteroid in cases with a severe index reaction (55.6% vs 17.4%, P = .02). Changing the iodinated contrast media resulted in an additional reduction of the breakthrough reaction rate overall (14.9% vs 32.1%, P = .001). In a total severity-based stratified prophylaxis regimens and changing iodinated contrast media can be considered in patients with a history of previous hypersensitivity reaction to iodinated contrast media to reduce the risk of breakthrough reactions. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. [Hypersensitivity to metals in patients with orthopedic implants].

    PubMed

    Sánchez Olivas, Manuel Anastacio; Valencia Zavala, Martha Patricia; Sánchez Olivas, Jesús Alberto; Sepúlveda Velázquez, Guadalupe

    2010-01-01

    All metals in contact with biological systems suffer corrosion, which is an electrochemical process that causes metallic ions formation, known as haptens, which link with endogenous or exogenous proteins, therefore inducing an immune response. A hypersensitivity response to an implanted material should be suspected when cutaneous lesions or inflammatory reactions occur proximal to or surrounding the site of the metallic orthopedic implant. At present there is no a reliable diagnostic test for the determination of hypersensitivity to implanted metallic devices. It has been shown that the products of corrosive degradation are associated with dermatitis, urticaria and vasculitis. Cutaneous lesions in patients with unsuccessful metallic implants are more frequent than in non-rejected implants or the general population. Although the cellular and humoral hypersensitivity response in metallic orthopedic implants has been clearly identified, the risk is very low. Nowadays the importance of hypersensitivity to metals as a contributing factor in the failure of implants is unknown.

  11. Hypersensitivity Reactions to Implanted Metal Devices: Facts and Fictions.

    PubMed

    Teo Wendy, Z W; Schalock, P C

    The use of metals in the medical field has become increasingly prevalent over the past few decades. Patients find themselves being exposed to metals in a variety of ways, ranging from external exposure to instruments such as the stainless steel in surgical blades to internal exposure via medical devices being implanted in their bodies. There has been growing interest in the possibility of developing hypersensitivity reactions to constituent metals in medical implant devices, both in cutaneous and systemic forms. Hypersensitivity reactions to metals are uncommon, but they are reported and require appropriate evaluation and management, particularly if they are symptomatic. In view of the lack of consensus in the field on the appropriate steps to evaluate and manage patients with suspected metal hypersensitivity reactions, this review aims to analyze current evidence on hypersensitivity reactions to metallic implants in orthopedic surgery, endovascular surgery, obstetrics and gynecology, and dental surgery.

  12. Total Knee Arthroplasty Failure Induced by Metal Hypersensitivity.

    PubMed

    Gupta, Ryan; Phan, Duy; Schwarzkopf, Ran

    2015-08-17

    Metal hypersensitivity is an uncommon complication after total knee arthroplasty (TKA) that can lead to significant functional impairment and aseptic prosthesis failure. 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. 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.

  13. The cough hypersensitivity syndrome: a novel paradigm for understanding cough.

    PubMed

    Morice, Alyn H

    2010-01-01

    For many years patients with chronic cough have been investigated in an attempt to diagnose the cause of the cough. Here I suggest that the overwhelming majority of patients with chronic cough have a single diagnosis: cough hypersensitivity syndrome. This is demonstrated by the homogeneous nature of the clinical history and investigational results of patients attending cough clinics. The hypersensitivity facet of the syndrome is demonstrated by objective testing with capsaicin and other protussive agents. Within the cough hypersensitivity syndrome there are different phenotypes. Those patients with a predominantly Th2-type immune response will develop eosinophilic inflammation and either cough-variant asthma or eosinophilic bronchitis. Those with predominantly heartburn symptoms will have a phenotype that reflects GERD and cough. However, the similarities between the different phenotypes far outweigh differences in a unifying diagnosis of the cough hypersensitivity syndrome, providing a more rational understanding of chronic cough.

  14. Allergic and hypersensitivity reactions in the intensive care unit.

    PubMed

    Kanji, Salmaan; Chant, Clarence

    2010-06-01

    Hypersensitivity reactions are defined as immunologically based adverse reactions to chemicals or medicinal agents. These reactions are common in the intensive care unit and can present as a simple, mildly symptomatic rash or as life-threatening anaphylactic reactions. Hypersensitivity reactions have traditionally been classified as types I to IV reactions based on the underlying immune mechanisms, although the clinical relevance of the classification is unclear, and new subtypes to this system have been recently proposed. Given the immunologic and often unpredictable nature of these reactions, avoidance or prevention is not a feasible option. Therefore, management has primarily consisted of withdrawal of potential offending agents, supportive therapy, symptomatic management, and, in some specific examples, targeted pharmacotherapy. This article outlines the background and types of hypersensitivity reactions and provides descriptions and management strategies when applicable to common types of hypersensitivity reactions encountered in the intensive care unit.

  15. Effectiveness of Lasers in the Treatment of Dentin Hypersensitivity

    PubMed Central

    Asnaashari, Mohammad; Moeini, Masoumeh

    2013-01-01

    Dentin hypersensitivity (DH) is a relatively common painful condition among dental problems. Although many studies have been performed regarding the diagnosis and treatment of DH, dental practitioners are still confused about the definite diagnosis and treatment.The use of lasers as a treatment for dentin hypersensitivity was first introduced in 1985.Laser treatment in dentin hypersensitivity is an interesting and controversial issue and many investigations have been done on its mechanism of action, advantages, and unclear points.The present literature review tries to go over the definition, diagnosis, etiology , predisposing factors, various laser types in the treatment of DH alone or in combination with topical desensitizing agents. Since a certain treatment has not yet introduced for dentin hypersensitivity, a combination of laser therapy and topical desensitizing factors ,can increase the success of the treatment compared with either treatments alone. PMID:25606300

  16. Low Ubiquinone Content in Escherichia coli Causes Thiol Hypersensitivity

    PubMed Central

    Zeng, H.; Snavely, I.; Zamorano, P.; Javor, G. T.

    1998-01-01

    Thiol hypersensitivity in a mutant of Escherichia coli (IS16) was reversed by complementation with a plasmid that carried the ubiX gene. The mutant had low ubiquinone content. Complementation elevated the ubiquinone level and eliminated thiol hypersensitivity. Analysis of chromosomal ubiX genes indicated that both parent and mutant strains were ubiX mutants. The low ubiquinone content of IS16 was possibly caused by a ubiD ubiX genotype. A ubiA mutant also exhibited thiol hypersensitivity. Neither IS16 nor the ubiA mutant strain could produce alkaline phosphatase (in contrast to their parent strains) after 2 h of induction, thus showing Dsb− phenotypes. The phenomena of thiol hypersensitivity and low ubiquinone content may be linked by their connections to the periplasmic disulfide bond redox machinery. PMID:9658014

  17. Nonsteroidal anti-inflammatory drug hypersensitivity among children.

    PubMed

    Guvenir, Hakan; Dibek Misirlioglu, Emine; Vezir, Emine; Toyran, Muge; Ginis, Tayfur; Civelek, Ersoy; Kocabas, Can N

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAID) are the second-most frequent drugs that cause hypersensitivity reactions among children. Studies related to NSAIDs hypersensitivity in children are limited. In this study, we aimed to evaluate children admitted with suspicion of NSAIDs reaction. Between January 1, 2011, and November 30, 2014, we included patients with suspicion of NSAIDs hypersensitivity in our clinic. For evaluation, skin tests and oral provocation tests with the drug (suspected or alternative) were proposed. Reactions were classified and defined according to the latest European Academy of Allergy and Clinical Immunology position paper on NSAID hypersensitivity. During the study period, 123 patients (with 136 drug reactions) were admitted to our clinic with suspected NSAID hypersensitivity. The mean (standard deviation) age of the patients, 67 female (55%), was 83.10 ± 56.05 months. Thirteen patients described reactions to more than one chemically unrelated NSAID, and 110 patients described reactions with chemically similar drugs. Eight patients were not included because they did not have provocation tests. Thus, 115 patients were evaluated. A hundred and thirty provocations were performed. Twenty patients (17.4%) were diagnosed with NSAID hypersensitivity (13 patients diagnosed by provocation tests and 7 patients diagnosed according to their history). The most frequently encountered agent was ibuprofen (50% [10/20]). Eighty percent (16 patients) of the reactions were considered "non-cross-reactive type." Fifteen patients (75%) were classified as having single-NSAID-induced urticaria and/or angioedema, three patients were classified as having NSAID-induced urticaria and/or angioedema, one patient was classified as having NSAID-exacerbated respiratory disease, and the other patients were classified as having single-NSAID-induced delayed hypersensitivity reactions. Detailed history and drug provocation tests are important to verify NSAID hypersensitivity

  18. Non-steroidal anti-inflammatory drug hypersensitivity in children.

    PubMed

    Alves, C; Romeira, A M; Abreu, C; Carreiro-Martins, P; Gomes, E; Leiria-Pinto, P

    There are rather few publications about hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAID) in the paediatric age. In this study, we aimed to assess the frequency of confirmed NSAID hypersensitivity in children with a previous reported reaction to NSAID in order to investigate the role of the drug provocation test (DPT) in the diagnostic workup and to explore the factors associated with confirmed NSAID hypersensitivity. We conducted a retrospective analysis of the clinical files from every patient under 18 years old who attended two Portuguese paediatric allergy outpatient clinics, from January 2009 to August 2014, due to a suspected NSAID hypersensitivity. We included 119 patients, with a median age of nine years (P25-P75: 5-14). Ibuprofen was the commonest implicated NSAID in the patients' reports (n=94-79%). After DPT, NSAID hypersensitivity was confirmed in nine (7.6%) patients, excluded in 93 (78.2%) and was inconclusive in 17 (14.3%). In the majority (n=95-79.8%), the reaction occurred in the first 24h after intake. Eighty-four patients (70.6%) reported only cutaneous manifestations and 18 (15.1%) had systemic symptoms. Anaphylaxis represented a relative risk to NSAID hypersensitivity confirmation. No association was found for atopy and the number of previous reactions. In our study, NSAID hypersensitivity was confirmed in a small proportion of the patients with a previous reported reaction. Ibuprofen was the most implicated drug with urticaria/angio-oedema as the commonest manifestation. Anaphylaxis was associated with confirmed drug hypersensitivity. The drug provocation test was essential to establish the diagnosis. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

  19. [Anticonvulsant hypersensitivity syndrome: an entity to be remembered].

    PubMed

    Crespo Pérez, Laura; Moreira Vicente, Víctor; Cano Ruiz, Ana; Gobernado Serrano, José María; Cobo Ibañez, Natalia; Milicua Salamero, José María

    2009-12-01

    Anticonvulsant hypersensitivity syndrome is an unpredictable, potentially fatal drug reaction to aromatic anticonvulsants such as carbamazepine, phenytoin and phenobarbital. The hallmark features include fever, eosinophilia, rash and involvement of one or more internal organs. Clearly established diagnostic criteria and treatment guidelines are lacking. A high index of suspicion is required to identify this syndrome, allowing early withdrawal of the drug and avoiding re-exposure. We report an illustrative case of anticonvulsant hypersensitivity syndrome and review the published literature.

  20. Type I immediate hypersensitivity reaction to cyanocobalamin but not hydroxycobalamin.

    PubMed

    Moloney, F J; Hughes, R; O'Shea, D; Kirby, B

    2008-07-01

    We report a case of a 42-year-old woman with a background of autoimmune polyglandular syndrome, who developed a type I immediate hypersensitivity reaction to intramuscular cyanocobalamin. Intradermal testing showed a positive reaction to cyanocobalamin. The patient was subsequently treated with intramuscular hydroxycobalamin after negative intradermal testing to this alternative B(12) compound. A review of previously described cases of hypersensitivity to either compound provides a rationale for the management of this rare but serious side-effect.

  1. Hypersensitivity due to ceftriaxone mimicking measles in a child.

    PubMed

    Arulraj, Russelian; Venkatesh, Chandrasekaran; Chhavi, Nanda; Soundararajan, Palanisamy

    2013-01-01

    Ceftriaxone is a commonly used antibiotic in children for various infections like respiratory tract infection, urinary tract infection and enteric fever. Hypersensitive reactions following ceftriaxone therapy are uncommon but are potentially life-threatening. The rash can resemble viral exanthems and may lead to a delay in the recognition and prompt treatment. Here we report a 7-year-old boy who presented with fever and rash with emphasis on recognizing ceftriaxone hypersensitivity and its management.

  2. Chemoembolization of Hepatocellular Carcinoma with Drug-Eluting Beads Complicated by Interstitial Pneumonitis

    PubMed Central

    Aladdin, Mohammed; Ilyas, Mohammed

    2011-01-01

    Transarterial chemoembolization has proven benefit in the treatment of unresectable hepatocellular carcinoma (HCC). Commonly reported symptoms following chemoembolization with or without drug-eluting beads include abdominal pain, nausea, and low-grade fever, which typically limited resolve within a few days. A recent study comparing traditional chemoembolization versus chemoembolization with drug-eluting beads demonstrated similar survival between the two techniques, but improved tolerability when the drug-eluting beads were used. This case report describes a patient with unresectable HCC undergoing chemoembolization with drug-eluting beads. The postprocedure course was complicated by interstitial pneumonitis secondary to shunting of the drug-eluting beads containing doxorubicin to both lungs via tumor vasculature. This case highlights the relationship between the number and size of the tumors to be treated, arteriovenous shunting within the liver/tumors, and the size of the embolization particles. PMID:22654266

  3. 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

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

    PubMed Central

    Chung, Min Jae; Lee, Jae Hee

    2015-01-01

    Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease. Mesalizine for the first-line therapy of UC has adverse effects include pancreatitis, pneumonia and pericarditis. UC complicated by two coexisting conditions, however, is very rare. Moreover, drug-related pulmonary toxicity is particularly rare. An 11-year-old male patient was hospitalized for recurring upper abdominal pain after meals with vomiting, hematochezia and exertional dyspnea developing at 2 weeks of mesalizine therapy for UC. The serum level of lipase was elevated. Chest X-ray and thorax computed tomography showed interstitial pneumonitis. Mesalizine was discontinued and steroid therapy was initiated. Five days after admission, symptoms were resolved and mesalizine was resumed after a drop in amylase and lipase level. Symptoms returned the following day, however, accompanied by increased the serum levels of amylase and lipase. Mesalizine was discontinued again and recurring symptoms rapidly improved. PMID:26770905

  5. Neonatal isolated rectal bleeding and the risk of hypersensitivity syndromes.

    PubMed

    Reiter, O; Morag, I; Mazkereth, R; Strauss, T; Maayan-Metzger, A

    2014-01-01

    When rectal bleeding occurs in an otherwise asymptomatic child, it can be classified as isolated rectal bleeding (IRB). Among the different etiologies suggested for IRB, one of the most common is a hypersensitivity reaction of the bowel mucosa to digested antigens. The objective of this study was to assess the long-term outcomes and the risk of developing hypersensitivity syndromes among infants following an IRB event. A historical prospective comparative study was carried out. The study compared 77 infants who were born at the Sheba Medical Center in Israel during the period 2002 to 2009 and who experienced a neonatal IRB event to 77 infants with the same gestational age, but without IRB. Data were obtained from hospital records and from phone interviews with the parents regarding hypersensitivity syndrome between the ages of 3 and 10 years. The IRB group was not at an increased risk of developing a hypersensitivity syndrome or gastrointestinal symptoms compared to the control group. Longer duration of breast-feeding was found to be related to a lower incidence of hypersensitivity symptoms. An IRB event in the neonatal period does not increase the risk of developing hypersensitivity syndromes or food allergies during childhood.

  6. Metal Hypersensitivity and Orthopedic Implants: Survey of Orthopedic Surgeons.

    PubMed

    Hallock, Katherine; Vaughn, Natalie H; Juliano, Paul; Marks, James G

    There is no clear consensus among orthopedic surgeons concerning metal hypersensitivity screening and orthopedic implants. This study investigated practices and opinions about metal hypersensitivity and orthopedic implants via a survey administered to practicing orthopedists. A questionnaire was sent to members of the Pennsylvania Orthopaedic Society electronically. Respondents were asked about preoperative and postoperative screening habits concerning metal hypersensitivity and implants. Forty-four physicians completed the survey. Only 11% of respondents reported that they always or often screen patients for metal hypersensitivity. Fifty percent of respondents stated that they only rarely refer patients for patch testing (and the remainder never do). If, however, patients were found to have a positive patch test, most providers were very likely to use a different implant. Other respondents were skeptical of the relationship between metal hypersensitivity and implant failure. Dermatitis, pain, and loosening were common reasons for postoperative testing. Seventy percent of respondents said that patch testing rarely or never changed their decision making. This study is reflective of the lack of consensus between orthopedists regarding patch testing. It demonstrates the diversity of opinions among orthopedists, the need for additional dialogue between orthopedic and dermatology specialties, and the need for larger studies investigating outcomes and metal hypersensitivity.

  7. Visceral and Somatic Hypersensitivity in TNBS induced Colitis in Rats

    PubMed Central

    Zhou, QiQi; Price, Donald D.; Caudle, Robert M.; Verne, G. Nicholas

    2010-01-01

    Inflammation of visceral structures in rats has been shown to produce visceral/somatic hyperalgesia. Our objectives were to determine if trinitrobenzene sulfonic acid (TNBS) induced colitis in rats leads to visceral/somatic hypersensitivity. Male Sprague-Dawley rats (200g–250g) were treated with 20 mg of TNBS in 50% ethanol (n=40) or an equivalent volume of ethanol (n=40) or saline (n=25) via the colon. Colonic distension, Von-Frey, Hargreaves, and tail reflex test were used to evaluate for visceral, mechanical, and thermal sensitivity. The rats demonstrated visceral hypersensitivity at 2–28 days following TNBS (p<0.0001). The ethanol treated rats also demonstrated visceral hypersensitivity that resolved after day 14. TNBS treated rats demonstrated somatic hypersensitivity at days 14–28 (p<0.0001) in response to somatic stimuli of the hind-paw. TNBS colitis is associated with visceral and somatic hypersensitivity in areas of somatotopic overlap. This model of colitis should allow further investigation into the mechanisms of visceral and somatic hypersensitivity. PMID:17703363

  8. Clinical dose-volume histogram analysis in predicting radiation pneumonitis in Hodgkin's lymphoma

    SciTech Connect

    Koh, Eng-Siew; Sun, Alexander . E-mail: alex.sun@rmp.uhn.on.ca; Tu Huan Tran; Tsang, Richard; Pintilie, Melania; Hodgson, David C.; Wells, Woodrow; Heaton, Robert; Gospodarowicz, Mary K.

    2006-09-01

    Purpose: To quantify the incidence of radiation pneumonitis (RP) in a modern Hodgkin's lymphoma (HL) cohort, and to identify any clinically relevant parameters that may influence the risk of RP. Methods and Materials: Between January 2003 and February 2005, 64 consecutive HL patients aged 18 years or older receiving radical mediastinal radiation therapy (RT) were retrospectively reviewed. Symptomatic cases of radiation pneumonitis were identified. Dose-volume histogram parameters, including V{sub 13}, V{sub 2}, V{sub 3}, and mean lung dose (MLD), were quantified. Results: At a median follow-up of 2.1 years, the actuarial survival for all patients was 91% at 3 years. There were 2 (2/64) cases of Radiation Therapy Oncology Group (RTOG) Grade 2 RP (incidence 3.1%). Both index cases with corresponding V{sub 2} values of 47.0% and 40.7% were located in the upper quartile (2/16 cases), defined by a V{sub 2} value of {>=}36%, an incidence of 12.5% (p = 0.03). Similarly for total MLD, both index cases with values of 17.6 Gy and 16.4 Gy, respectively, were located in the upper quartile defined by MLD {>=}14.2 Gy, an incidence of 11.8% (2/17 cases, p = 0.02). Conclusions: Despite relatively high V{sub 2} values in this study of HL patients, the incidence of RP was only 3%, lower compared with the lung cancer literature. We suggest the following clinically relevant parameters be considered in treatment plan assessment: a V{sub 2} greater than 36% and an MLD greater than 14 Gy, over and above which the risk of RTOG Grade 2 or greater RP would be considered clinically significant.

  9. MCP-1 antibody treatment enhances damage and impedes repair of the alveolar epithelium in influenza pneumonitis.

    PubMed

    Narasaraju, T; Ng, H H; Phoon, M C; Chow, Vincent T K

    2010-06-01

    Recent studies have demonstrated an essential role of alveolar macrophages during influenza virus infection. Enhanced mortalities were observed in macrophage-depleted mice and pigs after influenza virus infection, but the basis for the enhanced pathogenesis is unclear. This study revealed that blocking macrophage recruitment into the lungs in a mouse model of influenza pneumonitis resulted in enhanced alveolar epithelial damage and apoptosis, as evaluated by histopathology, immunohistochemistry, Western blot, RT-PCR, and TUNEL assays. Abrogation of macrophage recruitment was achieved by treatment with monoclonal antibody against monocyte chemoattractant protein-1 (MCP-1) after sub-lethal challenge with mouse-adapted human influenza A/Aichi/2/68 virus. Interestingly, elevated levels of hepatocyte growth factor (HGF), a mitogen for alveolar epithelium, were detected in bronchoalveolar lavage samples and in lung homogenates of control untreated and nonimmune immunoglobulin (Ig)G-treated mice after infection compared with anti-MCP-1-treated infected mice. The lungs of control animals also displayed strongly positive HGF staining in alveolar macrophages as well as alveolar epithelial cell hyperplasia. Co-culture of influenza virus-infected alveolar epithelial cells with freshly isolated alveolar macrophages induced HGF production and phagocytic activity of macrophages. Recombinant HGF added to mouse lung explants after influenza virus infection resulted in enhanced BrdU labeling of alveolar type II epithelial cells, indicating their proliferation, in contrast with anti-HGF treatment showing significantly reduced epithelial regeneration. Our data indicate that inhibition of macrophage recruitment augmented alveolar epithelial damage and apoptosis during influenza pneumonitis, and that HGF produced by macrophages in response to influenza participates in the resolution of alveolar epithelium.

  10. 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

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

    PubMed Central

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

    2015-01-01

    Pneumonic plague is a fatal disease caused by Yersinia pestis that is associated with a delayed immune response in the lungs. Because neutrophils are the first immune cells recruited to sites of infection, we investigated the mechanisms responsible for their delayed homing to the lung. During the first 24 hr after pulmonary infection with a fully virulent Y. pestis strain, no significant changes were observed in the lungs in the levels of neutrophils infiltrate, expression of adhesion molecules, or the expression of the major neutrophil chemoattractants keratinocyte cell-derived chemokine (KC), macrophage inflammatory protein 2 (MIP-2) and granulocyte colony stimulating factor (G-CSF). In contrast, early induction of chemokines, rapid neutrophil infiltration and a reduced bacterial burden were observed in the lungs of mice infected with an avirulent Y. pestis strain. In vitro infection of lung-derived cell-lines with a YopJ mutant revealed the involvement of YopJ in the inhibition of chemoattractants expression. However, the recruitment of neutrophils to the lungs of mice infected with the mutant was still delayed and associated with rapid bacterial propagation and mortality. Interestingly, whereas KC, MIP-2 and G-CSF mRNA levels in the lungs were up-regulated early after infection with the mutant, their protein levels remained constant, suggesting that Y. pestis may employ additional mechanisms to suppress early chemoattractants induction in the lung. It therefore seems that prevention of the early influx of neutrophils to the lungs is of major importance for Y. pestis virulence. Indeed, pulmonary instillation of KC and MIP-2 to G-CSF-treated mice infected with Y. pestis led to rapid homing of neutrophils to the lung followed by a reduction in bacterial counts at 24 hr post-infection and improved survival rates. These observations shed new light on the virulence mechanisms of Y. pestis during pneumonic plague, and have implications for the development of novel

  12. Mouse Model of Halogenated Platinum Salt Hypersensitivity ...

    EPA Pesticide Factsheets

    Occupational exposure to halogenated platinum salts can trigger the development of asthma. Concern for increased asthma risk exists for the general population due to the use of platinum (Pt) in catalytic converters and its emerging use as a diesel fuel additive. To investigate airway responses to Pt, we developed a mouse model of Pt hypersensitivity. Previously, we confirmed the dermal sensitizing potency of ammonium hexachloroplatinate (AHCP) using an ex vivo [3H]methyl thymidine labeling version of the local lymph node assay in BALB/c mice. Here, we investigated the ability of AHCP to induce airway responses in mice sensitized by the dermal route. Mice were sensitized through application of 100 µL 1% AHCP in DMSO to the shaved back on days 0, 5 and 19, and 25 µl to each ear on days 10, 11 and 12. Unsensitized mice received vehicle. On day 24, mice were challenged by oropharyngeal aspiration (OPA) with 0 or 100 µg AHCP in saline. Before and immediately after challenge, airway responses were assessed using whole body plethysmography (WBP). On day 26, changes in ventilatory responses to methacholine (Mch) aerosol were assessed by WBP; dose-dependent increases in Mch responsiveness occurred in sensitized mice. Bronchoalveolar lavage fluid harvested from sensitized mice contained an average of 7.5% eosinophils compared to less than 0.5% in control mice (p < 0.05). This model will be useful for assessing both relative sensitizing potency and cross-reacti

  13. Dentin hypersensitivity: Recent trends in management

    PubMed Central

    Miglani, Sanjay; Aggarwal, Vivek; Ahuja, Bhoomika

    2010-01-01

    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

  14. Type III Hypersensitivity Reaction in Mushroom Growers

    PubMed Central

    Choi, Byoung-Whui; Min, Kyung-Up; Kim, You-Young; Moon, Hee-Bom; Chang, Suk-II; Kang, Seock-Young; Kim, Sang-Jae; Kim, Sin-Ok

    1991-01-01

    Some respiratory symptoms in mushroom growers such as mushroom worker’s lung develop by inhalation of certain agents arising from the environment of mushroom cultivation. Recently we observed mushroom workers who had respiratory symptoms which might be type III hypersensitivity reaction to the antigen of Pleurotus floridae. We gave questionaires to all the mushroom growers at one of the biggest cultivation areas of mushrooms, Pleurotus floridae in Pocheon, Kyunggi Province. Those with respiratory symptoms were subjects for the study. CBC, chest X-ray, pulmonary function test, skin test with Pleurotus floridae extract, and precipitin antibody test to Pleurotus floridae were performed in the study subjects. Out of a total 308 mushroom workers, 23 workers (14 males, 9 females) had respiratory symptoms. Their mean age was 45 years, and their mean duration of engagement was 3.4 years. Their main symptoms were cough (100%), sputum (82.6%), dyspnea (43.5%), and fever with chills (13.0%). Two cases showed increased interstitial lung markings on chest X-ray films. Sixteen cases (73.9%) showed precipitin antibodies against P. floridae extract by counterimmunoelectrophoresis. Antibodies against Micropolyspora faeni and Thermoactinomyces vulgaris were not detected in any subject. PMID:1742253

  15. Immediate and delayed type hypersensitivity to malathion.

    PubMed

    Schanker, H M; Rachelefsky, G; Siegel, S; Katz, R; Spector, S; Rohr, A; Rodriquiz, C; Woloshin, K; Papanek, P J

    1992-12-01

    Between December 1989 and June 1990, 1,874 reports of alleged malathion application related illness from repeated spraying of a mixture of malathion corn syrup bait to eradicate a Mediterranean fruit fly infestation in Southern California were received by the Toxics Epidemiology Program of Los Angeles County. Among these complaints were 47 reports of urticaria, 38 reports of angioedema and 213 reports of a nonspecific skin rash. In order to determine whether these alleged skin reactions were the result of an immediate or delayed type of hypersensitivity reaction to malathion or to the corn syrup bait we studied ten subjects referred for testing by the local health department. All ten subjects had no reaction on patch testing. One child exhibited a positive reaction to the bait and one child had irritant reactions to malathion and to the bait. This study documented one case of a possible immediate IgE reaction to malathion bait. Due to the low participation rates in this study, no specific conclusions concerning the rate of sensitivity in the population can be drawn, although it appears that such reactions are uncommon.

  16. Visceral pain hypersensitivity in functional gastrointestinal disorders.

    PubMed

    Farmer, A D; Aziz, Q

    2009-01-01

    Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders whose diagnostic criteria are symptom based in the absence of a demonstrable structural or biochemical abnormality. Chronic abdominal pain or discomfort is a defining characteristic of these disorders and a proportion of patients may display heightened pain sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity (VPH). We examined the most recent literature in order to concisely review the evidence for some of the most important recent advances in the putative mechanisms concerned in the pathophysiology of VPH. VPH may occur due to anomalies at any level of the visceral nociceptive neuraxis. Important peripheral and central mechanisms of sensitization that have been postulated include a wide range of ion channels, neurotransmitter receptors and trophic factors. Data from functional brain imaging studies have also provided evidence for aberrant central pain processing in cortical and subcortical regions. In addition, descending modulation of visceral nociceptive pathways by the autonomic nervous system, hypothalamo-pituitary-adrenal axis and psychological factors have all been implicated in the generation of VPH. Particular areas of controversy have included the development of efficacious treatment of VPH. Therapies have been slow to emerge, mainly due to concerns regarding safety. The burgeoning field of genome wide association studies may provide further evidence for the pleiotropic genetic basis of VPH development. Tangible progress will only be made in the treatment of VPH when we begin to individually characterize patients with FGIDs based on their clinical phenotype, genetics and visceral nociceptive physiology.

  17. Handedness as a marker for drug hypersensitivity.

    PubMed

    Coren, S

    1998-04-01

    Several causal observations and a few recent studies suggest that left-handers may have greater reactivity to various drugs. A sample of 747 adults was surveyed to determine if they had had signs of hypersensitivity to commonly prescribed pharmaceutical drugs. Left-handers were significantly more likely to experience constipation, dizziness, and skin rashes, and were nearly three times more likely to experience other, miscellaneous, negative drug reactions. In addition left-handers were nearly twice as likely to have experienced situations where their physician felt it necessary to reduce drug dosages because of unwanted side-effects of medication. A second experiment using 840 adults indicated that a potential confound that would result if left-handers simply used more medical drugs in general, which would then give them more occasions on which reactions could occur, does not explain these results. Mechanisms that might account for these differences in drug sensitivity include differences in brain morphology, birth stress related neuropathy, and differences in immune system responses, all of which have been found to differ as a function of handedness.

  18. 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.

  19. 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

  20. Pressure application measurement (PAM): a novel behavioural technique for measuring hypersensitivity in a rat model of joint pain.

    PubMed

    Barton, Nicola J; Strickland, Iain T; Bond, Susan M; Brash, Harry M; Bate, Simon T; Wilson, Alex W; Chessell, Iain P; Reeve, Alison J; McQueen, Daniel S

    2007-06-15

    Chronic joint pain affects physical well being and can lead to severe psychological and social problems, therefore successful long-term management is highly sought-after. No current behavioural measures of pain used in pre-clinical models mimic the clinical dolorimeter, which provides an objective measure of joint hypersensitivity. In this study we aim to use a novel behavioural readout alongside an established measure to mimic the multifactorial measurements taken in the clinic. Using the pressure application measurement (PAM) device a gradually increasing squeeze was applied across the knee joint of rats until the animal gave an indication of pain or discomfort. PAM and the incapacitance tester were used to detect joint hypersensitivity in a well-established rodent model of adjuvant-induced arthritis. Subsequently, the analgesic effects of prednisolone (1, 3 or 10 mg kg(-1)), morphine (3 mg kg(-1)) and celecoxib (15 mg kg(-1)) were assessed. Both PAM and the incapacitance tester detected a reversal of hypersensitivity 1h post-drug administration. Furthermore, the two readouts were highly correlated, and power analysis indicated that PAM was highly reproducible. In conclusion, PAM provides a novel, accurate behavioural tool for detecting a primary mechanical hypersensitivity in a rat model of chronic inflammatory joint pain.

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

    SciTech Connect

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

    2012-04-01

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

  2. [The influence of hypersensitivity to nickel, chrome and cobalt on the process of fracture healing in patients treated operatively by stable osteosynthesis].

    PubMed

    Dobiecki, Konrad; Zietek, Paweł; Kołodziej, Lukasz; Brzosko, Marek; Bohatyrewicz, Andrzej; Kedzierski, Michał

    2009-01-01

    The aim of the study was to evaluate the frequency of occurrence of the hypersensitivity to nickel, chrome and cobalt in patients with longbone fractures. Two groups of patients were compared. The first group was composed of those treated operatively by stable osteosynthesis with the use of metal implants. The control group consisted of patients who have never been operated. Additionally, the influence of recognized hypersensitivity on the process of fracture healing was estimated. The study group consisted of 80 and the control group of 65 patients. All patients were patch tested with metal salts. The correlation was sought between hypersensitivity to metal in the study group, and incidence of complications relating to fracture healing. There was no significant difference observed both in frequency of occurrence of hypersensitivity to nickel, chrome and cobalt among patients treated operatively, and those treated conservatively, as well. There was no correlation between occurrence of hypersensitivity to the ions of metals, and complications in the process of fracture healing.

  3. Genetic and ethnic risk factors associated with drug hypersensitivity.

    PubMed

    Kim, Seung-Hyun; Ye, Young-Min; Palikhe, Nami Shrestha; Kim, Jeong-Eun; Park, Hae-Sim

    2010-08-01

    The purpose of this article is to review the recent findings of studies reporting on the genetic and ethnic factors associated with hypersensitivity reactions to common drugs such as acetyl salicylic acid/NSAIDs, antibiotics, antituberculus medications, and other drugs including carbamazepine (CBZ), abacarvir, and allopurinol that can cause severe hypersensitivity reactions. Aspirin hypersensitivity has recently been associated with a variety of genetic polymorphisms associated with leukotriene overproduction, eosinophil infiltration, and histamine-related genes. Recently, beta-lactam antibiotic hypersensitivity has been reported to be associated with interleukin (IL)-4 and IL-13 receptors in Italian, Chinese, and French populations. Moreover, a significant association of CYP2E1 in the Chinese, NAT2 in Koreans and glutathione S-transferase genotypes in Caucasians has been reported with antituberculus drug-induced hepatitis. The association of the HLA-B*1502 allele with CBZ-induced Stevens-Johnson syndrome in Asian population has also recently been observed. Aspirin hypersensitivity has been associated with various genetic polymorphisms. Human leukocyte antigen (HLA)-related markers and a variety of genetic polymorphisms of leukotriene-related genes, eosinophil-related genes, and genes associated with immune function have been described according to ethnicity. The genetic mechanisms of antibiotic hypersensitivity have been reported in Italian, French, and Chinese populations in addition to antibiotics-induced cutaneous reactions in the Korean population. Most prior genetic studies on antituberculus drug-induced hepatitis have focused on a few drug-metabolizing enzymes such as cytochrome P450 and N-acetyltransferase 2. HLA-related markers associated with CBZ, lamotrigine, and abacavir-induced severe hypersensitivity reactions have been described.

  4. Isolation and Characterization of mAMSA-hypersensitive Mutants

    PubMed Central

    Rogojina, Anna T.; Nitiss, John L.

    2008-01-01

    Topoisomerase II (Top2) is the primary target for active anti-cancer agents. We developed an efficient approach for identifying hypersensitive Top2 mutants and isolated a panel of mutants in yeast Top2 conferring hypersensitivity to the intercalator N-[4-(9-acridinylamino)-3-methoxyphenyl]methanesulphonanilide (mAMSA). Some mutants conferred hypersensitivity to etoposide as well as mAMSA, whereas other mutants exhibited hypersensitivity only to mAMSA. Two mutants in Top2, changing Pro473 to Leu and Gly737 to Val, conferred extraordinary hypersensitivity to mAMSA and were chosen for further characterization. The mutant proteins were purified, and their biochemical activities were assessed. Both mutants encode enzymes that are hypersensitive to inhibition by mAMSA and other intercalating agents and exhibited elevated levels of mAMSA-induced Top2:DNA covalent complexes. While Gly737 → Val Top2p generated elevated levels of Top2-mediated double strand breaks in vitro, the Pro473 → Leu mutant protein showed only a modest increase in Top2-mediated double strand breaks but much higher levels of Top2-mediated single strand breaks. In addition, the Pro473 → Leu mutant protein also generated high levels of mAMSA-stabilized covalent complexes in the absence of ATP. We tested the role of single strand cleavage in cell killing with alleles of Top2 that could generate single strand breaks, but not double strand breaks. Expression in yeast of a Pro473 → Leu mutant that could only generate single strand breaks conferred hypersensitivity to mAMSA. These results indicate that generation of single strand breaks by Top2-targeting agents can be an important component of cell killing by Top2-targeting drugs. PMID:18723844

  5. 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.

  6. Acid hypersensitivity in patients with eosinophilic oesophagitis.

    PubMed

    Krarup, Anne Lund; Villadsen, Gerda Elisabeth; Mejlgaard, Else; Olesen, Søren Schou; Drewes, Asbjørn Mohr; Funch-Jensen, Peter

    2010-03-01

    Painful symptoms are prevalent in patients with eosinophilic oesophagitis but experimental data are sparse. The aim of this study was to compare the pain response to experimental oesophageal stimulation in 14 patients with eosinophilic oesophagitis and 15 healthy volunteers. A multimodal probe was placed in the oesophagus. The participants were subjected to mechanical, thermal and electrical pain stimuli followed by perfusion with 0.1 M HCl. Pain scores, referred pain areas and evoked brain potentials to electrical stimulation of the oesophagus were recorded. Patients tolerated significantly less acid perfused in the oesophagus (median 123 versus 200 ml; P = 0.02) and felt the burning sensation evoked by the acid earlier (median 2.0 versus 5.0 min; P = 0.01). Eight patients had coexisting gastro-oesophageal reflux disease. Six patients had pure eosinophilic oesophagitis, and this group felt the acid earlier than those with concomitant reflux or the healthy volunteers (median 0.8 versus 2.0 and 5.0 min; P = 0.03). There were no differences between patients and controls in the responses to mechanical or thermal stimulation (P > 0.4). Furthermore, no differences were found for the proxies of central nervous system sensitization (response to electrical stimulations, referred pain areas or evoked brain potentials; P > 0.1). Patients with eosinophilic oesophagitis are hypersensitive to acid perfused in the oesophagus, and pathophysiologic findings are likely confined to the peripheral tissue. Reflux from physiological acid may play a role in the symptoms of eosinophilic oesophagitis.

  7. Hypersensitivity myocarditis associated with ephedra use.

    PubMed

    Zaacks, S M; Klein, L; Tan, C D; Rodriguez, E R; Leikin, J B

    1999-01-01

    Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has not yet been associated with either ephedrine or its plant derivative ephedra. A 39-year-old African American male with hypertension presented to Rush Presbyterian St. Luke's Medical Center with a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. He was taking Ma Huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed a male in mild respiratory distress. The lung fields had rales at both bases without audible wheezes. Internal jugular venous pulsations were 5 cm above the sternal notch. Medical therapy with intravenous furosemide and oral enalapril was initiated upon admission. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated with azothioprine 200 mg daily and prednisone 60 mg per day with a tapering course over 6 months. Anticoagulation with warfarin and diuretics was initiated and angiotensin-converting enzyme inhibition was continued. Hydralazine was added later. One month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal (EFN 50%) and the patient asymptomatic. Ephedra (Ma Huang) is the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis.

  8. Basal serum tryptase is not a risk factor for immediate-type drug hypersensitivity during childhood.

    PubMed

    Cavkaytar, Ozlem; Karaatmaca, Betul; Arik Yilmaz, Ebru; Sahiner, Umit M; Sackesen, Cansın; Sekerel, Bulent E; Soyer, Ozge

    2016-11-01

    High serum basal tryptase (sBT) levels have been identified as a risk factor for both venom- and food-induced severe allergic reactions. The aim of this study was to compare sBT levels in children with different severity of actual drug hypersensitivity reactions (DHRs) with those of age- and sex-matched controls without any history of DHRs. Patients between 0 and 18 years of age with a history of immediate-type DHRs manifested in 0-6 h after the culprit drug intake were included. Following ENDA (European Network for Drug Allergy) inquiries, patients were evaluated with skin and/or provocation tests to define the actual drug-hypersensitive patients. Serum BT levels were determined for both patients and controls. Of 345 children, 106 patients (30.7%) [(58.5% male), median age (interquartile range) 8.0 years (4.2-12.2)] were diagnosed as drug hypersensitive. Ninety-eight controls were also included. The sBT levels of drug-hypersensitive patients with and without anaphylaxis and the control group were similar [2.6 (2.0-3.6) μg/l vs. 2.8 (1.6-4.3) μg/l vs. 2.6 (1.8-3.6) μg/l, respectively, (p > 0.05)]. The sBT levels of the patients with sole cutaneous symptoms 2.8 (1.6-4.3) μg/l, mild anaphylaxis 3.0 (1.9-4.9) μg/l, and moderate-to-severe anaphylaxis 2.6 (2.0-3.6) μg/l were also comparable (p > 0.05). The onset of DHRs [those occurring in 1 h (n = 87) or in 1-6 h (n = 19) after the drug intake], positive results with skin tests with the culprit drug, or the classification of the patients according to different age groups [(0-2 years), (2-6 years), (6-12 years), (12-18 years)] did not correlate with sBT levels. The sBT levels in children with actual drug hypersensitivity would not be a risk factor for severe systemic reactions on the contrary to children with allergic reactions to food or insect venom. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Hypersensitivity of bronchial asthmatics to cockroach in Taiwan. comparative study between American and German cockroaches.

    PubMed

    Tsai, J J; Kao, M H; Wu, C H

    1998-11-01

    This study was performed to test the hypersensitivity of asthmatics to American and German cockroaches, which are both common in Taiwan. A total of 236 asthmatic patients received skin prick test using allergen extracts from both American and German cockroaches, and 596 sera from asthmatic patients were analyzed for their specific IgE against German cockroach extract. The results of skin test showed that 39.4 and 36.4% asthmatic patients were hypersensitive to American and German cockroaches. Fifteen among 236 patients were only allergic to American cockroaches and 8 were only allergic to German cockroaches. Using the Pharmacia CAP system, 36% of the sera were found to contain the specific IgE to German cockroach extract. Eighty-nine sera positive for German cockroach extract were then tested for their reactivity to American cockroach extract using the fluoroallergosorbent test (FAST). Sixty among 89 (68%) of their sera contained American cockroach-specific IgE. The correlation coefficient between both parameters was r = 0.45. Immunoblot and immunoblot inhibition studies were performed to analyze the IgE-binding components and the cross-reactivity between American and German cockroaches. The results showed that there are different IgE-binding components between American and German cockroaches. Sera containing specific IgE to both species of cockroach were absorbed with both species of cockroach extracts. The specific IgE to German cockroaches can be absorbed by American cockroach extract in all selected sera and the specific IgE to American cockroaches can only partially be absorbed by German cockroaches. The nonabsorbed allergens in American cockroaches had molecular weights of 33 and 50 kD. In conclusion, one-third of the asthmatic population tested was allergic to cockroaches. Although most cockroach-hypersensitive patients were allergic to both American and German cockroaches, more asthmatic patients were allergic to American cockroaches in Taiwan. The use of

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

    PubMed Central

    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 effi ciently decrease serum methotrexate concentration. A rapid improvement of clinical symptoms and resolution of pulmonary opacifi cation 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. PMID:26312671

  11. Hypersensitivity reactions to aprotinin re-exposure in paediatric surgery.

    PubMed

    Siehr, Stephanie; Stuth, Eckehard; Tweddell, James; Hoffman, George; Troshynski, Todd; Jones, Deborah; Mitchell, Michael; Ghanayem, Nancy

    2010-02-01

    Hypersensitivity to aprotinin is low (1-3%) but more likely with re-exposure. The manufacturer issued a black box warning which lists aprotinin re-exposure within 1 year of prior exposure as a contraindication. We investigated the temporal relationship between re-exposure interval and hypersensitivity in children. With Human Research Review Board approval, charts of all patients exposed to aprotinin during cardiac surgery were reviewed. We extracted data for re-exposure interval and hypersensitivity to skin tests, intravenous test dosing or infusion of the loading dose. We defined systemic hypersensitivity as haemodynamic instability, respiratory symptoms or diffuse skin reaction temporally related to exposure. From March 1994 to June 2007, there were a total of 2333 aprotinin exposures in 1824 patients. A total of 509 re-exposures occurred in 381 patients: 280 in 244 patients with early (within 1 year) re-exposure and 229 in 222 patients with late (after 1 year) re-exposure. Thirteen systemic hypersensitivity reactions occurred in the 509 re-exposures (2.6%): two during skin testing and 11 during the loading dose. Although the incidence of local hypersensitivity was increased with early re-exposure (6/280 or 2.1% vs 0/229, p=0.019), the incidence of the systemic reaction was not different between early and late re-exposures (6/280 or 2.1% (CI 0.8-4.6%) vs 7/229 or 3.1% (CI 1.2-6.2%), p=0.6). Six patients with a previous hypersensitivity reaction had an additional re-exposure to aprotinin; one of these patients had a systemic reaction during the third exposure. The incidence and type of hypersensitivity to aprotinin re-exposure in our cohort is consistent with previous reports. Repeat exposure within 1 year did not increase the risk of systemic hypersensitivity. Copyright 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

  12. Effect of premedications in a murine model of asparaginase hypersensitivity.

    PubMed

    Fernandez, Christian A; Smith, Colton; Karol, Seth E; Ramsey, Laura B; Liu, Chengcheng; Pui, Ching-Hon; Jeha, Sima; Evans, William E; Finkelman, Fred D; Relling, Mary V

    2015-03-01

    A murine model was developed that recapitulates key features of clinical hypersensitivity to Escherichia coli asparaginase. Sensitized mice developed high levels of anti-asparaginase IgG antibodies and had immediate hypersensitivity reactions to asparaginase upon challenge. Sensitized mice had complete inhibition of plasma asparaginase activity (P = 4.2 × 10(-13)) and elevated levels of mouse mast cell protease 1 (P = 6.1 × 10(-3)) compared with nonsensitized mice. We investigated the influence of pretreatment with triprolidine, cimetidine, the platelet activating factor (PAF) receptor antagonist CV-6209 [2-(2-acetyl-6-methoxy-3,9-dioxo-4,8-dioxa-2,10-diazaoctacos-1-yl)-1-ethyl-pyridinium chloride], or dexamethasone on the severity of asparaginase-induced allergies. Combining triprolidine and CV-6209 was best for mitigating asparaginase-induced hypersensitivity compared with nonpretreated, sensitized mice (P = 1.2 × 10(-5)). However, pretreatment with oral dexamethasone was the only agent capable of mitigating the severity of the hypersensitivity (P = 0.03) and partially restoring asparaginase activity (P = 8.3 × 10(-4)). To rescue asparaginase activity in sensitized mice without requiring dexamethasone, a 5-fold greater dose of asparaginase was needed to restore enzyme activity to a similar concentration as in nonsensitized mice. Our results suggest a role of histamine and PAF in asparaginase-induced allergies and indicate that mast cell-derived proteases released during asparaginase allergy may be a useful marker of clinical hypersensitivity.

  13. Central and peripheral hypersensitivity in the irritable bowel syndrome

    PubMed Central

    Zhou, QiQi; Fillingim, Roger B.; Riley, Joseph L.; Malarkey, William B.; Verne, G. Nicholas

    2010-01-01

    Previous investigations of somatic hypersensitivity in IBS patients have typically involved only a single stimulus modality, and little information exists regarding whether patterns of somatic pain perception vary across stimulus modalities within a group of patients with IBS. Therefore, the current study was designed to characterize differences in perceptual responses to a battery of noxious somatic stimuli in IBS patients compared to controls. A total of 78 diarrhea-predominant and 57 controls participated in the study. We evaluated pain threshold and tolerance and sensory and affective ratings of contact thermal, mechanical pressure, ischemic stimuli, and cold pressor stimuli. In addition to assessing perceptual responses, we also evaluated differences in neuroendocrine and cardiovascular responses to these experimental somatic pain stimuli. A subset of IBS patients demonstrated the presence of somatic hypersensitivity to thermal, ischemic, and cold pressor nociceptive stimuli. The somatic hypersensitivity in IBS patients was somatotopically organized in that the lower extremities that share viscerosomatic convergence with the colon demonstrate the greatest hypersensitivity. There were also changes in ACTH, cortisol, and systolic blood pressure in response to the ischemic pain testing in IBS patients when compared to controls. The results of this study suggest that a more widespread alteration in central pain processing in a subset of IBS patients may be present as they display hypersensitivity to heat, ischemic, and cold pressor stimuli. PMID:20074857

  14. Central and peripheral hypersensitivity in the irritable bowel syndrome.

    PubMed

    Zhou, QiQi; Fillingim, Roger B; Riley, Joseph L; Malarkey, William B; Verne, G Nicholas

    2010-03-01

    Previous investigations of somatic hypersensitivity in IBS patients have typically involved only a single stimulus modality, and little information exists regarding whether patterns of somatic pain perception vary across stimulus modalities within a group of patients with IBS. Therefore, the current study was designed to characterize differences in perceptual responses to a battery of noxious somatic stimuli in IBS patients compared to controls. A total of 78 diarrhea-predominant and 57 controls participated in the study. We evaluated pain threshold and tolerance and sensory and affective ratings of contact thermal, mechanical pressure, ischemic stimuli, and cold pressor stimuli. In addition to assessing perceptual responses, we also evaluated differences in neuroendocrine and cardiovascular responses to these experimental somatic pain stimuli. A subset of IBS patients demonstrated the presence of somatic hypersensitivity to thermal, ischemic, and cold pressor nociceptive stimuli. The somatic hypersensitivity in IBS patients was somatotopically organized in that the lower extremities that share viscerosomatic convergence with the colon demonstrate the greatest hypersensitivity. There were also changes in ACTH, cortisol, and systolic blood pressure in response to the ischemic pain testing in IBS patients when compared to controls. The results of this study suggest that a more widespread alteration in central pain processing in a subset of IBS patients may be present as they display hypersensitivity to heat, ischemic, and cold pressor stimuli.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. Epidermal growth factor upregulates serotonin transporter and its association with visceral hypersensitivity in irritable bowel syndrome.

    PubMed

    Cui, Xiu-Fang; Zhou, Wei-Mei; Yang, Yan; Zhou, Jun; Li, Xue-Liang; Lin, Lin; Zhang, Hong-Jie

    2014-10-07

    To investigate the role of epidermal growth factor (EGF) in visceral hypersensitivity and its effect on the serotonin transporter (SERT). A rat model for visceral hypersensitivity was established by intra-colonic infusion of 0.5% acetic acid in 10-d-old Sprague-Dawley rats. The visceral sensitivity was assessed by observing the abdominal withdrawal reflex and recording electromyographic activity of the external oblique muscle in response to colorectal distension. An enzyme-linked immunosorbent assay was used to measure the EGF levels in plasma and colonic tissues. SERT mRNA expression was detected by real-time PCR while protein level was determined by Western blot. The correlation between EGF and SERT levels in colon tissues was analyzed by Pearson's correlation analysis. SERT function was examined by tritiated serotonin (5-HT) uptake experiments. Rat intestinal epithelial cells (IEC-6) were used to examine the EGF regulatory effect on SERT expression and function via the EGF receptor (EGFR). EGF levels were significantly lower in the rats with visceral hypersensitivity as measured in plasma (2.639 ± 0.107 ng/mL vs 4.066 ± 0.573 ng/mL, P < 0.01) and in colonic tissue (3.244 ± 0.135 ng/100 mg vs 3.582 ± 0.197 ng/100 mg colon tissue, P < 0.01) compared with controls. Moreover, the EGF levels were positively correlated with SERT levels (r = 0.820, P < 0.01). EGF displayed dose- and time-dependent increased SERT gene expressions in IEC-6 cells. An EGFR kinase inhibitor inhibited the effect of EGF on SERT gene upregulation. SERT activity was enhanced following treatment with EGF (592.908 ± 31.515 fmol/min per milligram vs 316.789 ± 85.652 fmol/min per milligram protein, P < 0.05) and blocked by the EGFR kinase inhibitor in IEC-6 cells (590.274 ± 25.954 fmol/min per milligram vs 367.834 ± 120.307 fmol/min per milligram protein, P < 0.05). A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT

  20. Colonic N-methyl-d-aspartate receptor contributes to visceral hypersensitivity in irritable bowel syndrome.

    PubMed

    Qi, Qingqing; Chen, Feixue; Zhang, Wenxue; Wang, Peng; Li, Yanqing; Zuo, Xiuli

    2017-04-01

    N-methyl-d-aspartate receptor (NMDAR) in brain, spinal cord, and enteric nervous system is involved in visceral hypersensitivity. This study aimed to reveal the functional expression of NMDAR on mucosal cells in colon and to investigate the downstream signal pathway from colonic NMDAR activation to visceral hypersensitivity in irritable bowel syndrome (IBS). The expression of mucosal NMDAR in IBS patients and healthy controls was assessed by immunohistochemistry and Western blot and correlated with abdominal pain/discomfort scores quantified by a validated questionnaire. Electromyography recording in response to colorectal distension was recorded to measure the colonic sensitivity of mice receiving NMDA administration intracolonically. Brain-derived neurotrophic factor (BDNF) expression and extracellular signal-regulated kinase (ERK) pathway activation were examined in human colonic epithelial HT29 cells after NMDA stimulation, with or without MK801 or U0126 pretreatment. A significant upregulation of mucosal NMDAR was observed in IBS patients compared with controls, which was significantly correlated with abdominal pain/discomfort scores. Intracolonic administration of NMDA in normal mice produced increased colonic sensitivity to colorectal distension and elevated expression of BDNF and activation of ERK. Activation of NMDAR in colonic epithelial HT29 cells in vitro induced increased BDNF secretion in cell supernatants and higher BDNF expression in cells, as well as elevated phosphorylated ERK. This study demonstrated that the activation of mucosal NMDAR in colon may contribute to the visceral hypersensitivity in IBS, by increasing production of BDNF in an ERK-dependent pathway. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  1. 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

  2. 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.

  3. 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.

  4. Pro and Contra: Provocation Tests in Drug Hypersensitivity

    PubMed Central

    Soyer, Ozge; Sahiner, Umit Murat; Sekerel, Bulent Enis

    2017-01-01

    Drug provocation test (DPT) is the controlled administration of a drug to diagnose immune- or non-immune-mediated drug hypersensitivity and the last step for accurate recognition of drug hypersensitivity reactions when the previous diagnostic evaluations are negative or unavailable. A DPT is performed only if other conventional tests fail to yield conclusive results. In each clinical presentation, “to provoke or not to provoke” a patient should be decided after careful assessment of the risk–benefit ratio. Well-defined benefits of DPT include confirmative exclusion of diagnoses of drug hypersensitivity and provision of safe alternatives. However, disadvantages such as safety, difficulty in interpretations of results, lack of objective biomarkers, risks of resensitization, efficiency in daily practice, and lack of standardized protocols, are poorly debated. This review summarizes the current published research concerning DPT, with particular emphasis on the advantages and disadvantages of DPT in an evidence-based manner. PMID:28677662

  5. Colloidal silica-induced hypersensitivity: myth or reality.

    PubMed

    Ben Fredj, Nadia; Ben Fadhel, Najeh; Chaabane, Amel; Chadly, Zohra; Ben Romdhane, Haifa; Boughattas, Abderrazzek; Aouam, Karim

    2016-02-01

    Many excipients have been reported to induce drug hypersensitivity (e.g. colouring additives, preservatives). Colloidal silica has never been reported to induce drug hypersensitivity reactions. We report herein a 40-year-old patient who developed a skin eruption 2 days after Voltarene(®) (diclofenac) intake, confirmed by a positive patch test. Investigation of cross reactivity, assessed by patch testing to other non steroidal anti-inflammatory drugs, have showed a positive reaction only to piroxicam (Piroxen(®)), ketoprofen (Oki(®)) and indometacin (Indocid(®)). A hypersensivity to colloidal silica, a common excipient, was suspected. A patch test to this compound was performed showing a positive reaction. Colloidal silica, a compound widely used in drug manufacturing, could be another culprit excipient in inducing skin hypersensitivity reactions.

  6. Hypersensitivity to proton pump inhibitors: lansoprazole-induced Kounis syndrome.

    PubMed

    Vlahos, Nicholas P; Vavilis, George K; Giannelou, Ageliki G; Georgopoulou, Christina N; Kommata, Varvara J; Kougias, Constantinos T; Tsartsalis, Dimitrios N; Kounis, George N; Mazarakis, Andreas; Batsolaki, Maria; Gouvelou-Deligianni, Geogia V; Hahalis, George; Kounis, Nicholas G

    2009-05-29

    Proton pump inhibitors are commonly used in clinical practice for the treatment of peptic ulcer and gastroesophageal reflux and are well tolerated by the patients. Their use is rarely associated with hypersensitivity and anaphylactic reactions. According to the reports in the Uppsala Monitoring Center database the frequency of hypersensitivity reactions out of all reported adverse reactions for proton pump inhibitors and H2-histamine receptor antagonists was between 0.2% and 0.7%. A few cases of hypersensitivity to lansoprazole have been reported. We report a patient who developed Kounis syndrome after taking 30 mg of lansoprazole. This is the first report of Kounis syndrome associated with lansoprazole administration in the world literature.